How do you measure macular pigment?

Peter Ivins and Craig McArthur report on an objective method of measuring macular pigment using the new Zeiss Visucam 200 Peter Ivins and Craig McArthur report on an objective method of measuring macular pigment using the new Zeiss Visucam 200 Continual advances in science, technology and modern medicine have significantly increased life expectancy in the UK.1
This increase coincides with a projected epidemic rise in age-related macular degeneration (AMD) induced visual impairment,2-3 which is now the leading

cause of irreversible vision loss in the developed world.4-10 AMD accounts for the highest proportion of the estimated one million visually impaired people in the UK,2 90 per cent of whom are aged 65 years or over.11-12 The UK is predicted to have around 16 million people over the age of 60 by 2040.1 This demographic shift towards an elderly population means AMD will represent an increasing socioeconomic problem in the coming decades.

Current therapeutic interventions are expensive and limited to a small subgroup of exudative- AMD sufferers.13-17 Furthermore, there are currently no available treatments for non-exudative AMD patients. As a result prevention, delay or modification of AMD progression may offer a realistic means of minimising not only the socioeconomic burden, but the impact of this degenerative disorder on the vision-related quality of life for the individual.17

The exact aetiopathogenesis of AMD remains unclear;18-19 however a myriad of putative risk factors have been postulated, reviewed and researched in recent years, often with contradictory outcomes. The general consensus sub divides AMD risk factors into two categories: Non-modifiable and modifiable. Non-modifiable risk factors include age, genetics, Caucasian race, female gender, light iris pigmentation, hyperopia and diabetes. Modifiable risk factors include carotenoid deficiency, smoking, obesity, cataract surgery, cumulative UV light exposure, cardiovascular disease, diet lacking antioxidants, elevated serum lipids, alcohol consumption and sedentary lifestyle. As gatekeepers to vision care, optometrists could play an important role in reducing healthcare costs and increasing patient wellbeing by actively screening their patients for risk of AMD.

At present two conceivable and complimentary theories explaining the pathogenesis of AMD have come to prominence: reactive oxygen species (ROS) and oxidative damage from cumulative blue light exposure.20-23 As a result a variety of nutrients including omega-III fatty acids, vitamins A, C and E, and minerals zinc and selenium have been studied and epidemiologically linked with reduced risk and diminished progression of AMD.24 Several large independent epidemiological studies have also indicated that dietary xanthophyll carotenoids, lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ), collectively known as macular pigment (MP), may play a protective role against AMD by acting as a filter to phototoxic blue light and a free radical scavenger.25 The optical, antioxidant and anatomic properties of MP offer an increasingly plausible hypothesis for MP as a protective agent, which may help ameliorate AMD prevention.26

Therefore, the notion that measuring, monitoring and increasing MP as part of a routine screening and prevention programme has gained credence in recent times. This has led to the development of numerous systems for measurement of MP in both the laboratory and practice setting. These include objective procedures: fundus reflectometry, fundus autofluorescence and Raman spectroscopy and subjective measures: heterochromatic photometry and apparent motion photometry. Currently, heterochromatic flicker photometry (HFP) is the most widely used method for measurement of MP,27-29 particularly in the practice setting in the form of the  Macuscope, and MPODTM devices. This method generally requires visual acuity of 6/12 or better and an alert, cooperative patient. It has been reported in the literature30 and is the authors’ view based on several hundred measurements, that HFP is associated with high variability in subjects with poor visual acuity, low MP optical density and poor fixation. Such limitations are largely due to the time consuming and subjective nature of the technique.

It is interesting therefore that the new Visucam 200 by Zeiss offers an objective, fast and reportedly repeatable measurement of macular pigment using single wave fundus reflectometry. This may address some of the limitations of previously used HFP methodologies.

Zeiss Visucam 200

The instrument itself is housed in the familiar and typically Germanic, robust, armoured and highly clinical style of previous Zeiss retinal cameras (Figure 1). The new Visucam 200 comprises of a high quality retinal camera and macular pigment measurement technology combined within one unit, meaning the required footprint (410mm wide, 480mm deep and 650mm high, and weighs 30kg) is effectively halved when compared to separate HFP device and retinal camera. This, together with an integrated computer, is an attractive feature in our increasingly crowded test and equipment rooms (Figure 2).

Retinal camera

The retinal camera delivers excellent 14 bit colour images, in a variety of viewing angles including standard 45 degrees, 30 degrees and a small pupil mode allowing clear imaging in pupils as small as 3.3mm. There are several very useful imaging options including red-free imaging, for easier visualisation of retinal vasculature; multiple image montaging allowing for wide field capturing (Figure 3), useful in diabetic screening and retinal pathology; and 3D imaging for comparing stereo pairs, useful in optic nerve head evaluation. Capturing an image is a simple process due to the largely automated nature of the task. The Visucam 200 exploits autofocus and auto flash optimisation, meaning the only manual process is aligning working distance dots. Auto functionality allows for fast and confident image capture by untrained or auxiliary staff members.

Macular pigment measurement

Measuring macular pigment with the Visucam 200 involves exactly the same largely automated procedure as taking a retinal image and in the same time frame of a only few seconds per measurement. This procedure means with no additional training any staff member currently able to take a retinal photograph is now capable of accurately measuring macular pigment levels. This objective and straightforward process is in stark contrast to HFP?s subjective and time consuming methodology, which involves a level of experience and knowledge of the procedure to elicit accurate results from the patient, which may limit the technique to the
practitioner alone.

The Visucam 200 measures MP utilising single wave blue-reflection fundus imaging. This process involves measuring the reflectance of short wavelength light near the absorption maximum of MP at 460nm. Age-related compensation for the stray light effect of the elderly crystalline lens or the lack thereof in pseudoaphakic eyes is incorporated into MP optical density calculations. This methodology produces a quasithree dimensional distribution of MP in the macula, allowing for extrapolation of four parameters from the distribution: maximal optical density (maximum MPOD level), mean optical density, MP volume and MP area.

Macular Pigment – Data interpretation

The results are presented as a concise one-screen summary (Figure 4) allowing for quick assessment and comparison with previously recorded measurements. The results are illustrated in the form of a graphical representation of MP level, useful for serial analysis of MP fluctuations over time; a retinal image, useful for orientation and to ensure the scan has been taken correctly; and a colour-coded 3D topographical view of MP distribution, which facilitates patient education and explanation of MP location, function and distribution. The data produced and presentation formats are beneficial to the patient and practitioner alike when compared to results obtained from HFP methods; which normally consist of a single measurement of maximal MPOD. There is some suggestion in the literature that tracking only changes to maximum MPOD levels may not be sufficient, if monitoring the beneficial effects of nutritional supplementation on MP, and that volume levels may also be of importance.30 Therefore, the Visucam 200?s ability to measure maximal optical density, mean optical density, MP volume and MP area may prove advantageous as a result, if utilised as part of the armamentarium of a macular screening and monitoring programme.

Macular Pigment measurements – The Limitations

As with all the aforementioned methodologies for measuring MP in vivo there are potential limitations. The disadvantage of single-wave fundus reflectometry is that it requires normal retinal architecture; therefore results may become erroneous in patients with advanced AMD. The relevance of MP measurements in patients with advanced AMD is somewhat questionable; as a result, this limitation is a minor one. From a practical perspective, small pupils can be problematic and lead to inaccurate results; similar to the limitations of most non-mydriatic retinal cameras. However, the use of mydriatics in patients with pupils less than 3.3mm, for other techniques such as indirect ophthalmoscopy and retinal photography, is now commonplace in routine optometric practice, thus limiting the impact of this problem.
Presently the main limitation of the Visucam 200 is the lack of normative data for the various MP results produced. Until such data is published and available, the technique cannot be fully utilised. However, fluctuations in MP levels over time can be monitored once a baseline scan has been conducted, meaning improvement of MP levels with nutritional supplementation can be accurately assessed objectively. The test correlates well with other methodologies,30 meaning currently accepted advice regarding the maximum MPOD level can be assumed and used as a starting point for nutritional supplementation in patients considered to be lower than normal.

Verdict

The MP capability of the new Zeiss Visucam 200 appears to offer practitioners a fast, repeatable and most importantly an objective method of measuring and monitoring MP. This feature, either as a stand-alone measure or preferably combined with OCT, retinal imaging and AMD risk assessment software, means that optometrists now stand in a unique position to make a real difference to the potential visual outcomes of this and future ageing populations, by implementing comprehensive macular screening programmes. When one considers the significant investment in time, equipment and training that has been directed towards glaucoma screening by the profession over the last two decades and compare this with AMD with a threefold greater prevalence, then the emergence of new technology and research in macular screening techniques may see this area of clinical practice follow a similar path. One would expect other camera manufacturers to follow this technology addition to their platforms, but right now together with the imaging quality of the Zeiss Visucam and the practice integration capabilities of the Forum software, may mean that the buying decision of a potential retinal camera purchaser may tip towards Zeiss. Not only does it offer practitioners a useful additional clinical tool, but a potential revenue stream in macular screening and consequently a faster return on the investment required.

Macular screening clinic

You can make an appointment within our macular screening clinic to assess your risk of developing macular d

References

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