Testing the Repeatability of the QM2 Densitometer

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08/02/20 Sciences Reference this

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Methodology

Participants will be required to sit in for two separate sessions of recording within a two-week interval. To avoid the effects of diurnal variations, the second session will be arranged at a similar time of day as the first session. Retinal densitometry will be conducted for only one eye on both sessions. A demonstration video of the procedure will be shown to participants before one drop of two different mydriatics, 1.0% Tropicamide and 2.5% Phenylephrine, is instilled into the test eye. An eye patch is placed over the test eye before adjustments are made to the seat and table height. The room light is turned off for dark adaptation to occur. After 30 minutes, participants will uncover the patched eye before retinal densitometry procedure is performed on the test eye.

Participant’s medical history, baseline measurements are taken only on the first session only. Measurements obtained include visual acuity (VA), Van Herick angle estimation (VH), intraocular pressure (IOP) measurements before the retinal densitometry procedure. Due to the use of mydriatic drops, Van Herick angles and history are checked to ensure participants safety from inducing acute angle closure glaucoma. Participants with previous history of an adverse reaction to mydriatic drops, history of photosensitive epilepsy, ocular conditions such as age-related macular degeneration, cataracts and poor general health, VA of less than 0.2 Logmar in better eye, narrow angles(VH<G3) and IOP greater than 21mmHg are excluded. Test eye is determined by the eye with the better VA. Post densitometry, OCT scans, axial length measurements, fundus photography and IOP measurement is conducted on both eyes.

Literature Review

Introduction

In recent years, age related macular degeneration (AMD) has become one of the world’s leading cause of blindness in developed countries. Although the precise pathogenesis of AMD remains unknown, studies have shown that changes in the retinal pigmented epithelium (RPE) plays a crucial role in AMD. In recent years, there is a growing body of evidence that patients with early to intermediate stages of AMD have a reduced ability to dark adapt under low light conditions. Hence, dark adaptometry that has been used to diagnose and monitor other ocular pathologies has been employed in recent studies to further investigate the relationship between the RPE and AMD.

Dark adaptation (DA) refers to the eye’s ability to see when entering from a bright to dim environment. Several studies have shown that individuals with early stages of AMD have delayed rod mediated DA (Flamendorf et al. 2015; Owsley et al. 2016). This refers to the rate of recovery of light sensitivity in total darkness after being exposed to bright lights is limited by the supply rate of 11 cis retinal to the rod photoreceptors from the RPE (ref).

Associations of impaired Dark Adaptation

Increasing evidence suggests that delayed DA is a sign of early AMD. Flamendorf et al. (2015) demonstrated that impaired DA was associated with increasing age and severity of AMD.

A longitudinal study by Owsley et al. (2016) also found that older adults with abnormal rod mediated DA despite having normal healthy macular health have 2 times higher risk of acquiring AMD than normal DA adults. The study had a large sample size of 325 participants, mean age was 67.8 years ranging from 60 to 86 years. Furthermore, of the 325 participants, approximately 80% of the sample had normal DA and healthy macular allowing the study to investigate the occurrence of early AMD within the 3-year study period.

Dark adaptometry and fundus appearance

Imaging of the fundus through various techniques such as optical coherence tomography (OCT) and fundus photography have been used in the investigation of AMD and other retinal conditions. However, there are limitations to these techniques. The physical appearance of these structures does not reveal subtle changes within the RPE such as DA.

A study by Lians et al (2017) investigated the relationship between DA and structural changes of the retina in AMD by optical coherence tomography (OCT) images of the macula with participant’s DA results. The study showed that presence of structural abnormalities in the scanned macula, within or outside the testing spot of the dark adaptometer used, AdaptDx, impaired DA. Thus, supporting the notion that DA is a useful sign in the investigation of AMD. However, it should be noted that the strength of this study’s result is hampered by its small sample size.

The study by Owsley et al (2016) utilized fundus photography in addition to DA measurements. The study found that despite the clinically normal appearance of the fundus through coloured fundus photography, DA was reduced in some patients (be more specific).

Current modern dark adaptometers used

(Bring all repeatability to the same scale in % [CoR value/(mean value of visit 1+2)/2) x 100%]-the lower the percentage, the more repeatable. Ideally, visit 1 and 2 little to no diff, 0%. However, not always the case due to human variability and factors.)

Jackson et al. (2006) investigated whether the Scotopic Sensitivity Tester 1(SST-1) could produce slowed DA in older healthy adults and early AMD patients compared to young healthy normal. They found that the SST-1 was able to demonstrate slowed DA between the healthy young and old age groups, which concurred with evidence established by past studies on DA and aging. However, no significant difference was found between early AMD and the older group. This showed that the SST-1 was not suitable to use for investigating DA in early AMD patients as it was unable to detect any difference between the effects of aging and AMD on DA. It was suggested that no difference was found was due to full field summation from the SST-1 which masked any macula dysfunction when compared to previous studies that measured DA in a discrete spot adjacent to the macula. However, this is unlikely the case as shown in the study by Lians et al (2017). Furthermore, the SST-1 has no analytical software and require visual inspection of the graph by the clinician to interpret the results. Another disadvantage to the SST-1 is that stimulus intensity, presentation of stimulus, tracking and recording of thresholds to a data sheet or graph are all manually done by the clinician. This can result in variabilities in the results based on examiner’s speed or technique. In addition, the repeatability of the SST-1 was not investigated further weakening the strength and validity of the results attained in the study.

Kiser et al. (2006) conducted a study to establish the reliability of dark adapted psychophysical measures in patients with severe vision loss. In the study, SST-1 was used to measure DA. It showed that the repeatability of the result was dependent on the severity of the condition. It also highlighted the limitations of the SST-1, the narrow range of intensities of the stimulus where the maximum intensity was too dim for evaluating patients with severely impaired rod sensitivity while the minimum intensity was too bright for good rod sensitivity. Furthermore, the bleaching intensity or duration was insufficient to fully bleach photopigments in advanced retinal conditions. Despite its limitations, the SST-1 could still be used for early AMD investigation based on the narrow range of intensities.

Patryas et al (2013) conducted a study investigating the repeatability for computer-based rod DA. The study employed cathode ray tubes (CRT) technology in combination with neutral density filters to assess DA in thirty-three normal subjects. The study showed that the technique used was highly repeatable for measuring rod mediated DA. However, a small sample size of the study cannot be used to represent the normal population. Furthermore, pupils were not dilated during the study and as a result, there was less control over the bleach. It is therefore, uncertain, if the repeatability will remain the same if the older age group were to have conditions like cataracts or senile miosis.

Gaffney et al. (2011) investigated the repeatability of the Goldmann-Weekers adaptometer. The study found that it could monitor the quick changes in thresholds in cone mediated DA and the results were repeatable between visits. It should be noted that repeatability could differ from other studies as the there is no standardized bulb wattage used in the adaptometer. (79.48/123.21= 65%)

Gaffney et al. (2013) then compared the repeatability of four psychophysical methods for measuring cone mediated DA. They compared three computer-based methods against the Goldmann–Weekers adaptometer. They found no significant difference between the repeatability of each method indicating that any of the methods can be employed to measure cone mediated DA. However, the use of cone mediated DA may not be comparable to rod mediated DA techniques due to the recovery pathway differences between rods and cones. Furthermore, cones are less affected than rods due to their physical structure/nature. As such, the use of cone mediated DA may not be ideal to use for investigating and categorizing early AMD.

Flamendorf et al. (2015) study also evaluated the repeatability of the AdaptRx. It showed that there was no significant difference in the test-retest differences between AMD group indicating that AMD severity did not affect repeatability. COR=4.4min

Tan et al. (2018) evaluated the repeatability of a new dark adapted chromatic perimeter (DACP) in non-neovascular AMD and aged matched controls. They found in both 505 nm and 620 nm stimuli, the test points were less repeatable in the peripheral retina than in the central retina (<10°). When comparing the AMD group with the control, there was greater variation in the results in both stimuli. It is important to note that the small sample size of 18 participants, of which 10 had intermediate AMD, resulting in an overestimation of the Coefficient of repeatability (CoR). Unlike previous adaptometers, the DACP is capable of measuring rod function at multiple locations in early AMD.

Retinal Densitometry

Retinal densitometry is a technique used to measure the recovery rate of visual pigments after bleaching of the retina. Unlike the psychophysical techniques of measuring DA which are subjective measures, retinal densitometry is an objective measurement. Different layers of the retina absorb and reflect different wavelengths of light.

The fundamental basis of retinal densitometry is to compare the reflection of different wavelength lights from the retina over time. To measure the recovery rates of visual pigments, reflected light from a light adapted eye (i.e. light that has been exposed to intense light) is compared with the reflected light of the same eye after DA.

References

  • Flamendorf, J., Agrón, E., Wong, W.T., Thompson, D., Wiley, H.E., Doss, E.L., Al-Holou, S., et al.(2015). Impairments in Dark Adaptation Are Associated with Age-Related Macular Degeneration Severity and Reticular Pseudodrusen. Ophthalmology122:2053–2062.
  • Gaffney, A.J., Binns, A.M. and Margrain, T.H. (2011). The repeatability of the Goldmann-Weekers adaptometer for measuring cone adaptation. Documenta Ophthalmologica122:71–75.
  • Gaffney, A.J., Binns, A.M. and Margrain, T.H. (2013). Measurement of cone dark adaptation: a comparison of four psychophysical methods. Documenta Ophthalmologica128:33–41.
  • Jackson, G.R., Felix, T. and Owsley, C. (2006). The Scotopic Sensitivity Tester-1 and the detection of early age-related macular degeneration1. Ophthalmic and Physiological Optics26:431–437.
  • Kiser, A.K., Mladenovich, D., Eshraghi, F., Bourdeau, D. and Dagnelie, G. (2006). Reliability and Consistency of Dark-Adapted Psychophysical Measures in Advanced Eye Disease. Investigative Opthalmology & Visual Science47:444.
  • Laíns, I., Miller, J.B., Park, D.H., Tsikata, E., Davoudi, S., Rahmani, S., Pierce, J., et al.(2017). Structural Changes Associated with Delayed Dark Adaptation in Age-Related Macular Degeneration. Ophthalmology124:1340–1352.
  • Owsley, C., Mcgwin, G., Clark, M.E., Jackson, G.R., Callahan, M.A., Kline, L.B., Witherspoon, C.D., et al.(2016). Delayed Rod-Mediated Dark Adaptation Is a Functional Biomarker for Incident Early Age-Related Macular Degeneration. Ophthalmology123:344–351.
  • Patryas, L., Parry, N.R.A., Carden, D., Baker, D.H., Kelly, J.M.F., Aslam, T. and Murray, I.J. (2013). Assessment of age changes and repeatability for computer-based rod dark adaptation. Graefes Archive for Clinical and Experimental Ophthalmology251:1821–1827.
  • Tan, R.S., Guymer, R.H. and Luu, C.D. (2018). Repeatability of Retinal Sensitivity Measurements Using a Medmont Dark-Adapted Chromatic Perimeter in Healthy and Age-Related Macular Degeneration Cases. Translational Vision Science & Technology7:3.
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