|Year : 2019 | Volume
| Issue : 1 | Page : 2-6
Assessment of macular pigment optical density using fundus reflectometry in diabetic patients
Mary Varghese, Joel Antony
Department of Ophthalmology, St. John's Medical College, Bengaluru, Karnataka, India
|Date of Web Publication||24-Apr-2019|
Dr. Mary Varghese
53, 3rd Cross, Dollar Layout, B.T.M. 1 st Stage, Bengaluru - 560 068, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
PURPOSE: Diabetic retinopathy (DR) is a major cause of visual disability and may be associated with reduction in macular pigment (MP) density and insufficient data are available. We present MP optical density (MPOD) measured by fundus reflectometry in eyes with and without early and moderate DR.
SUBJECTS AND METHODS: This was a cross-sectional study conducted in the year 2014–2015. Participants were divided into three groups: the normal individuals without diabetes constituted Group I, while diabetic patients without DR and the patients with mild-to-moderate DR constituted Group II and Group III, respectively. MPOD and maximum optical density (Max OD) were measured using a Visucam 500 fundus camera (Carl Zeiss Meditec AG, Jena, Germany).
RESULTS: Fifty diabetic patients without DR, 50 with mild and moderate DR, and 50 healthy individuals underwent MPOD and Max OD measurements. The mean pigment density was the same in all the three groups (0.12). HbA1c levels were inversely correlated with MPOD (P = 0.01) and Max OD (P = 0.002). There was no relationship between MP density and age (P = 0.66), gender (P = 0.24), or duration of diabetes (P = 0.85). The duration of diabetes was compared between the two groups of diabetic patients with and without DR.
CONCLUSIONS: The mean pigment density assessed by fundus reflectometry was 0.12 in each of the three groups studied. Higher HbA1c levels in diabetic patients correlated with decreased MPOD and Max OD. Better glycemic control may influence macular health in diabetic patients.
Keywords: Diabetic retinopathy, fundus reflectometry, macular pigment optical density
|How to cite this article:|
Varghese M, Antony J. Assessment of macular pigment optical density using fundus reflectometry in diabetic patients. Middle East Afr J Ophthalmol 2019;26:2-6
|How to cite this URL:|
Varghese M, Antony J. Assessment of macular pigment optical density using fundus reflectometry in diabetic patients. Middle East Afr J Ophthalmol [serial online] 2019 [cited 2020 Sep 27];26:2-6. Available from: http://www.meajo.org/text.asp?2019/26/1/2/256968
| Introduction|| |
Diabetic retinopathy (DR) and diabetic maculopathy are major causes of visual disability and blindness. With the increasing incidence of diabetes worldwide, the impact on patients' health as well as the burden on health care are expected to rise exponentially. There are data to suggest that reduction in macular pigment (MP) density may be related to the occurrence of DR and could possibly be an early marker of visual loss among diabetic individuals. Although many studies have been done to assess MP optical density (MPOD) using different techniques, limited data exist on reflectometry-based MPOD in diabetic patients, and to the best of our knowledge, there are no data in the Indian population.
MPs which include carotenoids lutein, zeaxanthin, and meso-zeaxanthin are located in the Henle fibers, and in the inner plexiform layer, with concentrations that peak at the center of the fovea., Oxidative stress and hyperglycemia are major factors in the pathophysiology of DR. Various mechanisms help protect the retina from oxidative stress and MP are seen to be powerful antioxidants which contribute to the protection., Level of MP in DR could be an indicator of the amount of oxidative stress and increased MP density could possibly reduce the occurrence of DR. Some studies have identified MPs as a potentially modifiable risk factor for age-related macular degeneration due to their antioxidant effects.,
In vivo measurement of MP has been tried using numerous techniques and its density is referred to as MPOD. The measurement techniques can broadly be classified as “psychophysical methods” which require a response from the subject and “objective methods,” which require minimal input from the subject. Psychophysical methods include heterochromic flicker photometry and minimum motion photometry. The objective methods include fundus reflectometry, fundus autofluorescence, resonance Raman spectroscopy, and visual-evoked potentials. Fundus reflectometry is the quantitative assessment of the amount of light reflected from the fundus, which can be used to measure optical density of the MPs and has been shown to be a reliable method. This technique uses single wavelength reflectometry for the assessment of MPOD. In this study, we used fundus reflectometry to study the effect of diabetes and its severity on MPOD.
| Subjects and Methods|| |
This prospective, cross-sectional comparative study included type 2 diabetic patients and normal controls. The study was approved by the Institutional Ethics Committee. The patients were divided into three groups of 50 each. The sample size was calculated using the comparison of two independent means based on the study by Lima et al. The minimum required sample size was 46, with a power of 90% and level of significance 0.05. The normal individuals constituted Group I, while diabetic patients without DR and the patients with mild-to-moderate DR constituted Group II and Group III, respectively. Patients with proliferative or severe nonproliferative DR were excluded from the study. Patients with diabetic macular edema, other macular disorders, and those who had undergone laser therapy or any ocular surgery were also excluded from the study.
All patients underwent complete ophthalmic examination which included best-corrected visual acuity, slit-lamp biomicroscopy, applanation tonometry, Amsler's grid assessment, and fundus examination.
Following adequate pupillary dilation, all patients were positioned in front of the fundus camera and instructed to maintain a steady fixation on the red fixation light. Fundus images were captured in the optional MPOD mode using Visucam 500 fundus camera (Carl Zeiss Meditec AG, Jena, Germany). Single wavelength reflectometry principle was used and reflectance of the fundus was based on a three-dimensional parabolic function. Three measurements were obtained at the same sitting and an average was taken. The measured MPOD was the mean of MP density obtained over a 30° area. Maximum optical density (Max OD), defined as the point where maximum pigment density was found in the macula was also measured [Figure 1].
|Figure 1: Measurement of macular pigment optical density and maximum optical density (image from Zeiss Visucam 500)|
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Descriptive statistics were computed for qualitative variables with frequency counts and percentages. Mean (± standard deviation [SD]) with the range was estimated for quantitative variables. Student's t-test and one-way ANOVA were used as inferential statistics for comparing the groups. Pearson's correlation was used to study the correlation between qualitative variables. All tests were done using SPSS (Statistical Package for the Social Sciences) version 16 software (SPSS Inc., Chicago, IL, USA) and statistical significance was considered whenever P < 0.05.
| Results|| |
We included 150 persons; 50 in each of the three groups in the study. Group I, healthy individuals without diabetes, had 18 males and 32 females; Group II, diabetics without DR had 32 males and 18 females and Group III, diabetics with mild-to-moderate DR, had 28 males and 22 females. The mean ages of Group I, II, and III were 49.3 ± 7.48, 53.6 ± 6.19, and 54.96 ± 7.35 years, respectively.
There was no significant difference in the mean (± SD) MPOD (0.12 + 0.01, P = 0.70) or in the Max OD (0.30 + 0.002, P = 0.29) between males and females [Table 1].
|Table 1: Comparison of macular pigment optical density and maximal optical density according to age and gender|
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Comparison of mean MPOD (± SD) between Groups I, II, and III was 0.12 with no statistically significant difference between the groups. The Max OD was 0.29, 0.31, and 0.30 in Groups I, II, and III, respectively (P = 0.06). There was no significant effect of age on MPOD or the Max OD between the three groups (P = 0.06 and 0.55, respectively).
Although there was no effect of duration of diabetes on the MPOD and Max OD (P = 0.85 and 0.39), there was a significant inverse correlation between HbA1c and MPOD as well as Max OD (P = 0.01 and 0.002) [Table 2].
|Table 2: Correlation of macular pigment optical density and maximal optical density according to age, duration of diabetes, and glycated hemoglobin|
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| Discussion|| |
We evaluated Mean MPOD and Max OD in 100 diabetic patients with and without retinopathy (50 patients each) and 50 nondiabetic control patients. There was no significant difference in the mean MPOD or Max OD among these three groups, but a significant inverse correlation was noted between HbA1c levels and the mean MPOD as well as the Max OD.
DR is an important cause for blindness. Hyperglycemia and oxidative stress are major factors involved in the pathophysiology of DR. Macular carotenoid pigments are considered to have antioxidant and anti-inflammatory protective effects. While the importance of MPOD in the pathogenesis of DR is not clear, reduced MPOD has been demonstrated in diabetic patients with or without retinopathy when compared with normal controls., Ford et al., found a significant reduction in the serum levels of macular carotenoids in newly diagnosed and established diabetic patients in the United States in comparison with normal individuals. Conversely, a study carried out by She et al. using heterochromatic flicker photometry to investigate the association between MPOD and diabetes in a Chinese population found no significant difference in the MPOD levels in diabetic patients with or without retinopathy.
MP comprised of carotenoids such as lutein and zeaxanthin which have been shown to protect against age-related macular degeneration. Since the MP is entirely of dietary origin, supplementation with lutein, zeaxanthin, and meso-zeaxanthin may reduce the risk of macular degeneration., A positive association was noted between MPOD levels, central foveal thickness and higher intake of foods containing carotenoids. Akuffo et al. also suggested that vision in patients with age-related macular degeneration could be enhanced by augmentation of MP. These findings suggest that MPs may be important in the pathogenesis of DR.
There are several postulated mechanisms by which MP level may be reduced in diabetic individuals. It has been suggested that MPOD levels might be genetically influenced. However, studies of MPOD in monozygotic twins have shown that pigment levels were not entirely genetically determined. A diabetic diet is known to be deficient in lutein and zeaxanthin, but Granado et al. found no significant difference in serum levels of lutein and zeaxanthin between insulin-dependent diabetic patients, first-degree relatives, and control groups.
MPOD and its significance in macular diseases has been studied using various techniques such as fundus autofluorescence, Raman spectroscopy, and heterochromic flicker photometry. However, there are only limited studies of MPOD using fundus reflectometry. Several studies have been done on age-related macular degeneration and MPOD, but the relationship between diabetes mellitus and MPOD has been evaluated only in limited number of studies., Lima et al. showed a significant inverse correlation between HbA1c levels and mean MPOD, which was also seen in our study. However, contrary to our findings, their study also showed reduced MPOD levels in diabetic patients with or without retinopathy when compared with nondiabetic individuals. Their study included patients with abnormalities in the macula, such as edema and ischemia, which could explain the differences in the results. Patients with advanced DR often have hazy media due to vitreous hemorrhage, traction retinal detachment involving the macula or ischemic macula, which could interfere and affect the measurement of MPOD. Our study only included diabetic patients with clinically normal macula and excluded those with previous retinal surgery, clinically significant macular edema or advanced retinopathy, which may have contributed to the similar mean MPOD or Max OD among diabetic and nondiabetic individuals.
In the study done by Lima et al., using modified confocal scanning laser ophthalmoscope, the mean MPOD measured 2.8° around the fovea, while in our study done using fundus reflectometry, the mean MPOD measurement was 30°. Using “foveal reflection analyzer,” Zagers et al. showed that although MPOD was not significantly altered in patients with Type 1 or Type 2 diabetes, the integrity of the photoreceptors in the fovea was altered in diabetics.
To assess the effect and duration of hyperglycemia, we studied the effect of HbA1c values and duration of diabetes on MPOD. There was a significant inverse correlation between HbA1c levels and MPOD and Max OD. Lower MPOD levels were seen with poor glycemic control, comparable to the findings by Lima et al. According to the previous reports, different mechanisms could lead to reduced MPOD in diabetic patients. These include genetic influence, deficiency of lutein and zeaxanthin in the diet, a reduced absorption from the gut,, a reduced rate of incorporation into the retinal tissue, and an increased rate of removal from the retina. Specific alterations in diabetes mellitus, such as thickening of basement membranes of the retinal capillaries, increased affinity of oxygen for glycosylated hemoglobin, a redox shift due to the effects of hyperglycemia on sorbitol metabolism, and abnormal vasculature in the parafoveal capillaries, imply that the retina in a diabetic patient is under continuous oxidative stress. Analyses of retinal tissues from primate and human eyes for oxidation products of lutein and zeaxanthin showed that these pigments play a role as antioxidants protecting the macula against photooxidative stress. This suggests that good glycemic control is the determining factor for optimal levels of MPOD and emphasizes the importance of maintaining an optimal HbA1c level in the prevention of retinopathy.
In our study, the severity of hyperglycemia seemed to adversely impact the MPOD and the Max OD. There was no correlation between the duration of diabetes and the MPOD or the Max OD suggesting that poor glycemic control rather than duration of diabetes is responsible for reduction of MPOD. The study by Scanlon et al. likewise did not find a correlation between MPOD levels and the duration of diabetes.
We did not find significant relationships between MPOD and age in our patients, a finding that is in agreement with the previous studies, although a small age-dependent decline has also been reported.,
Our study failed to show a significant influence of gender on the mean MPOD or Max OD. These results are in agreement with former studies that found no gender differences in MPOD.,, Information on use of lutein- or zeaxanthin-containing supplements or on dietary patterns were not included in the study. Therefore, one cannot exclude the possibility that unaccounted use of such supplements or dietary factors might have exerted a confounding effect in our study.
Max OD measurement at a point is a relatively new modality and limited data exist in diabetics. Even though mean MPOD can be altered by pre- or intraretinal scatter, a larger area of foveal assessment was done in MPOD evaluation by this method, unlike previous modalities. It also has the added advantage of having no confounding effect on anterior segment opacities as an eccentric reference point was taken. Therefore, fundus reflectance method can be considered a good option among the various modalities. To the best of our knowledge, this is the first report of MPOD in an Indian population using fundus reflectometry.
Our study objectively shows that MPOD is lower in diabetic patients with poor glycemic control. The exact role of hyperglycemia and duration of diabetes in the pathogenesis of retinopathy remains controversial. While studies have implicated poor glycemic control in the development of retinopathy, glycemic variability and sudden variations in blood glucose levels may be more important in its development. This may explain the lack of association between MPOD and the duration of diabetes. Since MPOD and Max OD were associated with HbA1c in our study, it may serve as an early marker for the development of retinopathy. We did not assess the influence of glycemic variability on MPOD and the development of retinopathy in our study.
Limitations of our study include the small sample size and exclusion of patients with advanced DR.
Fundus reflectometry is a simple technique to measure MPOD. Our study has demonstrated that MPOD measured using this technique was relatively unaffected by the presence or absence of diabetes. There was no significant correlation between age, gender or duration of diabetes, and the MPOD or the Max OD. However, higher HbA1c significantly correlated with a decreased MPOD and Max OD, thus suggesting the need for optimum control of blood sugar in diabetic patients. We feel that larger studies are warranted, especially in patients with severe nonproliferative and proliferative DR. If these findings are corroborated in large and prospective trials, MPOD measurement using fundus reflectometry may be considered as a useful screening tool to monitor the macular health in diabetic patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Lima VC, Rosen RB, Maia M, Prata TS, Dorairaj S, Farah ME, et al.
Macular pigment optical density measured by dual-wavelength autofluorescence imaging in diabetic and nondiabetic patients: A comparative study. Invest Ophthalmol Vis Sci 2010;51:5840-5.
Lima VC, Rosen RB, Farah M. Macular pigment in retinal health and disease. Int J Retina Vitreous 2016;2:19.
Trieschmann M, van Kuijk FJ, Alexander R, Hermans P, Luthert P, Bird AC, et al.
Macular pigment in the human retina: Histological evaluation of localization and distribution. Eye (Lond) 2008;22:132-7.
Hammond BR Jr., Wooten BR, Smollon B. Assessment of the validity of in vivo
methods of measuring human macular pigment optical density. Optom Vis Sci 2005;82:387-404.
Arden GB, Sivaprasad S. Hypoxia and oxidative stress in the causation of diabetic retinopathy. Curr Diabetes Rev 2011;7:291-304.
Akuffo KO, Nolan JM, Peto T, Stack J, Leung I, Corcoran L, et al.
Relationship between macular pigment and visual function in subjects with early age-related macular degeneration. Br J Ophthalmol 2017;101:190-7.
Howells O, Eperjesi F, Bartlett H. Measuring macular pigment optical density in vivo
: A review of techniques. Graefes Arch Clin Exp Ophthalmol 2011;249:315-47.
Berendschot TT, van Norren D. Objective determination of the macular pigment optical density using fundus reflectance spectroscopy. Arch Biochem Biophys 2004;430:149-55.
Meyers KJ, Johnson EJ, Bernstein PS, Iyengar SK, Engelman CD, Karki CK, et al.
Genetic determinants of macular pigments in women of the carotenoids in age-related eye disease study. Invest Ophthalmol Vis Sci 2013;54:2333-45.
Scanlon G, Connell P, Ratzlaff M, Foerg B, McCartney D, Murphy A, et al.
Macular pigment optical density is lower in type 2 diabetes, compared with type 1 diabetes and normal controls. Retina 2015;35:1808-16.
Ford ES, Will JC, Bowman BA, Narayan KM. Diabetes mellitus and serum carotenoids: Findings from the Third National Health and Nutrition Examination Survey. Am J Epidemiol 1999;149:168-76.
She CY, Gu H, Xu J, Yang XF, Ren XT, Liu NP, et al.
Association of macular pigment optical density with early stage of non-proliferative diabetic retinopathy in Chinese patients with type 2 diabetes mellitus. Int J Ophthalmol 2016;9:1433-8.
Ozyurt A, Kocak N, Akan P, Calan OG, Ozturk T, Kaya M, et al.
Comparison of macular pigment optical density in patients with dry and wet age-related macular degeneration. Indian J Ophthalmol 2017;65:477-81.
] [Full text]
Hammond BR Jr., Fuld K, Curran-Celentano J. Macular pigment density in monozygotic twins. Invest Ophthalmol Vis Sci 1995;36:2531-41.
Granado F, Olmedilla B, Gil-Martínez E, Blanco I, Millan I, Rojas-Hidalgo E, et al.
Carotenoids, retinol and tocopherols in patients with insulin-dependent diabetes mellitus and their immediate relatives. Clin Sci (Lond) 1998;94:189-95.
Zagers NP, Pot MC, van Norren D. Spectral and directional reflectance of the fovea in diabetes mellitus: Photoreceptor integrity, macular pigment and lens. Vision Res 2005;45:1745-53.
Hammond CJ, Liew SH, Van Kuijk FJ, Beatty S, Nolan JM, Spector TD, et al.
The heritability of macular response to supplemental lutein and zeaxanthin: A classic twin study. Invest Ophthalmol Vis Sci 2012;53:4963-8.
Wooten BR, Hammond BR Jr., Land RI, Snodderly DM. A practical method for measuring macular pigment optical density. Invest Ophthalmol Vis Sci 1999;40:2481-9.
Beatty S, Murray IJ, Henson DB, Carden D, Koh H, Boulton ME, et al.
Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population. Invest Ophthalmol Vis Sci 2001;42:439-46.
Hammond BR Jr., Caruso-Avery M. Macular pigment optical density in a southwestern sample. Invest Ophthalmol Vis Sci 2000;41:1492-7.
Delori FC, Goger DG, Hammond BR, Snodderly DM, Burns SA. Macular pigment density measured by autofluorescence spectrometry: Comparison with reflectometry and heterochromatic flicker photometry. J Opt Soc Am A Opt Image Sci Vis 2001;18:1212-30.
Jahn C, Wüstemeyer H, Brinkmann C, Trautmann S, Mössner A, Wolf S, et al.
Macular pigment density in age-related maculopathy. Graefes Arch Clin Exp Ophthalmol 2005;243:222-7.
Berendschot TT, Willemse-Assink JJ, Bastiaanse M, de Jong PT, van Norren D. Macular pigment and melanin in age-related maculopathy in a general population. Invest Ophthalmol Vis Sci 2002;43:1928-32.
Chatziralli IP. The role of glycemic control and variability in diabetic retinopathy. Diabetes Ther 2018;9:431-4.
[Table 1], [Table 2]