MACULAR PIGMENT DISTRIBUTION RESPONSES TO HIGH-DOSE ZEAXANTHIN SUPPLEMENTATION IN PATIENTS WITH MACULAR TELANGIECTASIA TYPE 2

Purpose: To analyze macular pigment (MP) amount and distribution in patients with macular telangiectasia Type 2 receiving oral zeaxanthin supplementation in a randomized, open-label, interventional trial. Methods: Eight macular telangiectasia Type 2 patients were randomized to 10 mg or 20 mg of zeaxanthin per day. At each visit, best-corrected visual acuity, contrast sensitivity, fundus biomicroscopy, color fundus photography, autofluorescence imaging, optical coherence tomography, and serum carotenoid levels were tested. Patients were assessed at baseline and after 6, 12, 18, and 24 months of zeaxanthin supplementation. Concentration of MP was analyzed and calculated from autofluorescence imaging obtained at 488-nm excitation wavelength. Serum carotenoid levels were obtained using high-performance liquid chromatography. Results: The majority of patients had definite increases in the intensity of hypofluorescent ring of MP, but none of them deposited MP centrally at the fovea. Although some patients noted subjective improvements in vision, no objective improvements could be documented, and there were no changes in foveal optical coherence tomographic features. Yellowish, hypofluorescent crystals appeared in one patient's macular region with no change in visual acuity. These inner retinal crystals disappeared several months after discontinuing her 20-mg zeaxanthin supplement. Conclusion: Based on the current study, zeaxanthin supplementation does not result in any visual benefit in patients with macular telangiectasia Type 2 and does not reestablish a normal peaked distribution of MP in the fovea. One patient developed a novel, reversible, crystalline maculopathy in response to zeaxanthin supplementation that was reminiscent of canthaxanthin crystalline maculopathy.

[1]  J. Nolan,et al.  Macular carotenoids and age-related maculopathy. , 2006, Annals of the Academy of Medicine, Singapore.

[2]  D. Pauleikhoff,et al.  MACULAR TELANGIECTASIA–CHANGES IN MACULAR PIGMENT OPTICAL DENSITY DURING A 5-YEAR FOLLOW-UP , 2014, Retina.

[3]  R. Bone,et al.  Stereochemistry of the human macular carotenoids. , 1993, Investigative ophthalmology & visual science.

[4]  E. Harrison,et al.  Xanthophylls are preferentially taken up compared with beta-carotene by retinal cells via a SRBI-dependent mechanism. , 2008, Journal of lipid research.

[5]  P. Bernstein,et al.  Crystalline Maculopathy Associated With High-Dose Lutein Supplementation. , 2016, JAMA ophthalmology.

[6]  R. Danis,et al.  Macular pigment: a review of current knowledge. , 2006, Archives of ophthalmology.

[7]  O. Sommerburg,et al.  Lutein and zeaxanthin are associated with photoreceptors in the human retina. , 1999, Current eye research.

[8]  J. Erdman,et al.  Absorption and Transport of Carotenoids , 1993, Annals of the New York Academy of Sciences.

[9]  H. Hense,et al.  Changes in macular pigment optical density and serum concentrations of its constituent carotenoids following supplemental lutein and zeaxanthin: the LUNA study. , 2007, Experimental eye research.

[10]  U. Schmidt-Erfurth,et al.  Effects of lutein supplementation on macular pigment optical density and visual acuity in patients with age-related macular degeneration. , 2011, Investigative ophthalmology & visual science.

[11]  B. Blodi,et al.  Idiopathic juxtafoveolar retinal telangiectasis , 1993 .

[12]  S. Beatty,et al.  The impact of macular pigment augmentation on visual performance using different carotenoid formulations. , 2012, Investigative ophthalmology & visual science.

[13]  D. Pauleikhoff,et al.  MACULAR TELANGIECTASIA: Patterns of Distribution of Macular Pigment and Response to Supplementation , 2010, Retina.

[14]  J. Gass,et al.  Idiopathic juxtafoveolar retinal telangiectasis. , 1982, Archives of ophthalmology.

[15]  J. Gass.  A fluorescein angiographic study of macular dysfunction secondary to retinal vascular disease. 3. Hypertensive retinopathy. , 1968, Archives of ophthalmology.

[16]  J. Gass.  A fluorescein angiographic study of macular dysfunction secondary to retinal vascular disease. II. Retinal vein obstruction. , 1968, Archives of ophthalmology.

[17]  N. Lamba,et al.  Medication induced retinal side effects. , 2014, Disease-a-month : DM.

[18]  S. Beatty,et al.  Augmentation of Macular Pigment Following Supplementation with All Three Macular Carotenoids: An Exploratory Study , 2010, Current eye research.

[19]  P. Bernstein,et al.  Ligand-binding characterization of xanthophyll carotenoids to solubilized membrane proteins derived from human retina. , 2001, Experimental eye research.

[20]  D. Schweitzer,et al.  Long term effects of lutein, zeaxanthin and omega-3-LCPUFAs supplementation on optical density of macular pigment in AMD patients: the LUTEGA study , 2013, Graefe's Archive for Clinical and Experimental Ophthalmology.

[21]  D. Snodderly,et al.  Measurement of carotenoids in human and monkey retinas. , 1992, Methods in enzymology.

[22]  François C Delori,et al.  Autofluorescence method to measure macular pigment optical densities fluorometry and autofluorescence imaging. , 2004, Archives of biochemistry and biophysics.

[23]  C. Creuzot-Garcher,et al.  Relationships of Macular Pigment Optical Density With Plasma Lutein, Zeaxanthin, and Diet in an Elderly Population: The Montrachet Study. , 2016, Investigative ophthalmology & visual science.

[24]  Usha Chakravarthy,et al.  Macular pigment and age-related macular degeneration: longitudinal data and better techniques of measurement are needed. , 2008, Investigative ophthalmology & visual science.

[25]  H. Scholl,et al.  ABNORMAL MACULAR PIGMENT DISTRIBUTION IN TYPE 2 IDIOPATHIC MACULAR TELANGIECTASIA , 2008, Retina.

[26]  Richard A. Bone,et al.  Optical density spectra of the macular pigmentin vivo andin vitro , 1992, Vision Research.

[27]  George Britton,et al.  UV/Visible Spectroscopy , 1995 .

[28]  R. Guymer,et al.  Perifoveal müller cell depletion in a case of macular telangiectasia type 2. , 2010, Ophthalmology.

[29]  L. Yannuzzi,et al.  Idiopathic Macular Telangiectasia , 2006, Retina.

[30]  A. Bird,et al.  Macular pigment parameters in patients with macular telangiectasia (MacTel) and normal subjects: implications of a novel analysis. , 2012, Investigative ophthalmology & visual science.

[31]  T. Berendschot,et al.  Quantification of reduced macular pigment optical density in the central retina in macular telangiectasia type 2. , 2009, Experimental eye research.

[32]  A. Rigotti,et al.  The role of the high-density lipoprotein receptor SR-BI in the lipid metabolism of endocrine and other tissues. , 2003, Endocrine reviews.

[33]  P. Bernstein,et al.  Identification of StARD3 as a lutein-binding protein in the macula of the primate retina. , 2011, Biochemistry.

[34]  D M Snodderly,et al.  The macular pigment. I. Absorbance spectra, localization, and discrimination from other yellow pigments in primate retinas. , 1984, Investigative ophthalmology & visual science.

[35]  P. Bernstein,et al.  Carotenoids as possible interphotoreceptor retinoid-binding protein (IRBP) ligands: a surface plasmon resonance (SPR) based study. , 2011, Archives of biochemistry and biophysics.

[36]  F. Khachik,et al.  Identification and quantitation of carotenoids and their metabolites in the tissues of the human eye. , 2001, Experimental eye research.

[37]  R. Bone,et al.  Lutein, zeaxanthin, and the macular pigment. , 2001, Archives of biochemistry and biophysics.

[38]  Binxing Li,et al.  Lutein, zeaxanthin, and meso-zeaxanthin: The basic and clinical science underlying carotenoid-based nutritional interventions against ocular disease , 2016, Progress in Retinal and Eye Research.

[39]  R. Bone,et al.  Analysis of the macular pigment by HPLC: retinal distribution and age study. , 1988, Investigative ophthalmology & visual science.

[40]  P. Bernstein,et al.  Identification and metabolic transformations of carotenoids in ocular tissues of the Japanese quail Coturnix japonica. , 2007, Biochemistry.

[41]  J. Gass.  A fluorescein angiographic study of macular dysfunction secondary to retinal vascular disease. V. Retinal telangiectasis. , 1968, Archives of ophthalmology.

[42]  D. Pauleikhoff,et al.  IDIOPATHIC MACULAR TELANGIECTASIA TYPE 2: DISTRIBUTION OF MACULAR PIGMENT AND FUNCTIONAL INVESTIGATIONS , 2010, Retina.

[43]  Chelsea E. Myers,et al.  SUPPLEMENTATION WITH THREE DIFFERENT MACULAR CAROTENOID FORMULATIONS IN PATIENTS WITH EARLY AGE-RELATED MACULAR DEGENERATION , 2014, Retina.

[44]  Paul S Bernstein,et al.  Identification and Characterization of a Pi Isoform of Glutathione S-Transferase (GSTP1) as a Zeaxanthin-binding Protein in the Macula of the Human Eye* , 2004, Journal of Biological Chemistry.

[45]  T. Berendschot,et al.  Confocal blue reflectance imaging in type 2 idiopathic macular telangiectasia. , 2008, Investigative ophthalmology & visual science.

[46]  J. Adib,et al.  The differential diagnosis of crystals in the retina , 2004, International Ophthalmology.

[47]  P. Borel,et al.  Genetic variants in BCMO1 and CD36 are associated with plasma lutein concentrations and macular pigment optical density in humans , 2011, Annals of medicine.

[48]  J. van de Kraats,et al.  Lutein and zeaxanthin measured separately in the living human retina with fundus reflectometry. , 2008, Investigative ophthalmology & visual science.

[49]  I. Boniuk,et al.  Crystalline retinopathy associated with long-term nitrofurantoin therapy. , 1994, Archives of ophthalmology.

[50]  Meidong Zhu,et al.  Loss of Müller's cells and photoreceptors in macular telangiectasia type 2. , 2013, Ophthalmology.

[51]  J. Edwards.  Zeaxanthin: Review of Toxicological Data and Acceptable Daily Intake , 2016, Journal of ophthalmology.

[52]  H. Dou,et al.  Effect of lutein and zeaxanthin on macular pigment and visual function in patients with early age-related macular degeneration. , 2012, Ophthalmology.

[53]  T. Creighton.  Methods in Enzymology , 1968, The Yale Journal of Biology and Medicine.

[54]  Werner Gellermann,et al.  Nonmydriatic fluorescence-based quantitative imaging of human macular pigment distributions. , 2006, Journal of the Optical Society of America. A, Optics, image science, and vision.

[55]  P. Bernstein,et al.  Retinal tubulin binds macular carotenoids. , 1997, Investigative ophthalmology & visual science.

[56]  P. Bernstein,et al.  Inactivity of human β,β-carotene-9′,10′-dioxygenase (BCO2) underlies retinal accumulation of the human macular carotenoid pigment , 2014, Proceedings of the National Academy of Sciences.