Dziuba and Sergienko: New Pathogenetic-Oriented Method of Treatment of the Dry Form of Age-Related Macular Degeneration



Problem statement and analysis of the recent research

Age-related macular degeneration (AMD) is a leading cause of irreversible loss of central vision in people older 60 years of age [13, 22, 33]. Much attention is paid to the study of etiology, pathogenesis, risk factors for this disease, and effective methods of prevention and treatment of AMD. One of the most important risk factors for AMD is decrease in the optical density of pigment in the macula [13, 14, 16, 17, 21, 27, 28, 32].

Carotenoids are pigments of macular area. There are about a thousand different carotenoids, but there are only two in the macular area of the retina. They are lutein and zeaxanthin, which are oxycarotenoids. 70 percent of lutein and zeaxanthin from their total content in the eye are concentrated in the macula. The concentration of carotenoids decreases from the center of the retina to its periphery. The density peak of carotenoids is located in the central macular area with a diameter of 100 microns [5, 10, 18]. Oxycarotenoids are localized in cell membranes and the highest concentrations of lutein and zeaxanthin is found in photoreceptor outer segment membranes [29]. The concentration of lutein and zeaxanthin in the macula is directly proportional to the macular pigment optical density (MPOD). Pigments provide optical light-filtering protection of visual cells and pigment epithelium from the damaging effect of blue light and both are highly effective inhibitors of free radicals. MPOD is reduced in case of AMD further increasing the effect of damaging factors on the retina [15, 19, 20, 21, 23, 26, 30].

Since lutein and zeaxanthin are not synthesized in the body, a large amount of research is devoted to the study of lutein-containing drugs influence on AMD prevention and treatment. High concentration of lutein and zeaxanthin in the food reduced the risk for AMD by 43-57% compared to a group of carotenoids low consumption [24]. The possibility of increase in MPOD on the background of high doses of lutein (12 mg) and zeaxanthin (0.6 mg) intake was confirmed by a 3-year randomized placebo controlled study with double blind control CARMA (2006) [25]. Similar results are observed in LUNA research (2007) [31]. According AREDS data, daily intake of 500 mg of vitamin C, 400 mg of vitamin E, 15 mg of beta-carotene, 80 mg of zinc as zinc oxide and 2 mg of copper as copper oxide lower the risk of significant vision loss by 25% in patients with moderate and developed changes in the macular region in case of AMD dry form [13]. The most large-scale randomized research AREDS2 (2006-2012) was based on 5-year follow-up of 4203 patients with non-exudative form of AMD.

AREDS2 results proved the effectiveness of lutein (10 mg) and zeaxanthin (2 mg) in preventing AMD progression and also the ability to replace β-carotene by carotenoids. β-carotene present in the AREDS formula (2001) is dangerous for people who smoke. The risk of late-stage AMD decreased from 34% to 30% [14].

Thus, the search for new possible ways of MPOD improvement in AMD treatment of is very important.

The objective of the research was to study the indices of macular pigment optical density in patients with the dry form of AMD after two courses of low-energy light therapy and conservative treatment.

Materials and methods

162 patients with the dry form of AMD were under our supervision. The main group (MG) consisted of 87 patients (146 eyes). These patients underwent two courses of low-energy light therapy (LLT) in combination with two courses of conservative treatment in hospital for 10 days each. The control group (CG) consisted of 75 patients (135 eyes). These patients underwent only two courses of conservative therapy in the hospital for 10 days each with intervals of six months. Observations in groups were conducted before, after the treatment, after 1, 3 and 6 months after the first treatment. Further, a second course of treatment was conducted with supervision at the same time. The total period of follow-up was 1 year. LLT was performed using the Spektra Light device (Version MARK III) (Canada, Vision Aid Inc., Winnipeg, MB, Canada, in cooperation with Star Fish Ltd., Victoria, BC). The procedure of transpupillary thermal therapy was perfomed by monochromatic pulsed light green, red and infrared spectra with energy of 2 x 10-6 J. Treatment consisted of 10 sessions of 5 minutes each for 10 days (1 session per day). The course of conservative therapy included: emoxypine, parabulbar injection in a dose of 0.5 ml number 5; meldonium, parabulbar injection in a dose of 0.5 ml number 5; meldonium i.m. in a dose of 4.0 ml number 5; tiotriazolini i.m. in a dose of 2.0 ml number 10; complex B vitamins, i.m., in a dose of 3.0 ml number 6; ascorbic acid i.m. in a dose of 1.0 ml number 10; deproteinized hemoderivate of calf blood i.m. in a dose of 2.0 ml number 10. All patients were generally conducted eye examination. MPOD was measured using densitometer “Maculux praxis” produced by Ebiga VISION GmbH, Germany, by heterochromatic flicker photometry. MPOD is measured in absolute numbers and the normal result is about 0.4 (according to the user). Patients who had psychophysiological disorders and could not adequately answer the questions were excluded from the observation group. The patients from main and control group did not take drugs containing lutein and zeaxanthin.

Statistical processing of the data was conducted using Excel (MS Office 2003, XP) and STATISTICA 6.0 application (StatSoft Inc., USA). Results of the research were presented as the average arithmetic and average error (M±m). Student’s t-test was used to assess differences in the normal distribution of samples. The difference between the compared indices in all cases was considered statistically significant at the level of significance of p<0.05.

Results of the research and their discussion

MPOD index increased from 0.249±0.011 units to 0.360±0.016 units, by 0.111±0.014 units (44.6%) in 1 month after the first course of treatment, up to 0.344±0.015 units, by 0.095±0.013 units (38.2%) in 3 months in MG patients (p<0.05). Indices increased to 0.321±0.014 units, by 0.072±0.013 (28.9%), (p<0.05) in 6 months after the first course of treatment Stabilization of the index from 0.248±0.012 units before the treatment and 0.243±0.011 6 months after the first course of treatment (p>0.05) occurred in patients of the KG.

The data concerning MPOD in patients before and after the first course of treatment are presented in Table 1 and Figure 1.

Table 1.

Indicators of macular pigment optical density in patients with AMD with dry form after the first course of treatment (n=281)

The term of observation MPOD indices, units
MG (n=146) CG (n=135)
Before the treatment 0.249±0.011 0.248±0.012
After 1 month 0.360±0.016*,▲ 0.260±0.012
After 3 months 0.344±0.015*,▲ 0.250±0.012
After 6 months 0.321±0.014*,▲ 0.243±0.011

Notes.

* – the level of significance of differences between indices of the main and control group at the same period of observation statistically significant (p<0.05).

▲ – the level of significance of differences between the indices inside the group before the treatment and at the appropriate term of observation statistically significant (p<0.05).

Fig. 1.

Comparison of macular pigment optical density in patients with the dry form of AMD after the first course of treatment

gmj-23-gmj.2016.3.47-g1.jpg

MPOD indices increased from 0.321±0.014 units to 0.431±0.017 units, by 0.110±0.016 units (34.3%) in 1 month after the second course of treatment, up to 0.412±0.017 units, by 0.091±0.016 units (28.4%) in 3 months, and up to 0.388±0.016 units, by 0.067±0.015 (20.9%) in 6 months (p<0.05) in patients of the MG.

The data concerning MPOD in patients before and after the second course of treatment are presented in Table 2 and Figure 2.

Table 2.

Indices of macular pigment optical density in patients with dry form AMD after the second course of treatment (n=281)

The term of observation MPOD indices, units
MG (n=146) CG (n=135)
Before the treatment 0.321±0.014* 0.243±0.011
After 1 month 0.431±0.017*,▲ 0.256±0.012
After 3 months 0.412±0.017*,▲ 0.243±0.011
After 6 months 0.388±0.016*,▲ 0.237±0.011

Notes.

* – the level of significance of differences between indices in the main and control group at the same period of observation statistically significant (p<0.05).

▲ – the level of significance of differences between the indices inside the group before the treatment and at the appropriate term of observation statistically significant (p<0.05).

Fig. 2.

Comparison of macular pigment optical density in patients with the dry form of AMD after the second course of treatment

gmj-23-gmj.2016.3.47-g2.jpg

Stabilization of the index from 0.243±0.011 units before the treatment and 0.237±0.011 in 6 months after the second course of treatment (p>0.05) was observed in patients of KG.

Some authors’ studies showed some effect of monochromatic coherent and incoherent light on various morphological structures of the retina. L.A. Linnyk and contributing authors detected increased DNA synthesis in the nuclei of neuroepithelium cells and ganglion cells after irradiation with low-intensity laser radiation (LLR) in case of degenerative diseases of the macular region. The mechanism of therapeutic action of laser stimulation in case of central chorioretinal dystrophy is associated with increased phagocytic activity of the retinal pigment epithelium and possibly with direct action of LLR on decomposition products of neuro-receptors [9]. Infrared laser detects a more intense effect on such structure as choroid [2].

Effects of low-yellow incoherent pulsed light lead to increased anabolic processes in intact retina and in case of experimental dystrophy [12]. Efficiency of light therapy treatment of retina and optic nerve pathologies, amblyopia has been proved [1, 3, 4, 8].

The literature does not present any data on the effect of coherent or incoherent monochromatic light on the low concentrations of lutein and zeaxanthin in the macula. MPOD increasing mechanism is unknown. Taking into account that central vision pigments in the body cannot be synthesized and are received with food, we may assume that low-energy light therapy activates endogenous mechanism of pigments income into the macula. This mechanism is probably realized through transportation macular pigments from other parts of the body. Low-energy pulsed monochromatic light of green, red and infrared spectra, like LLR plays the role of a trigger or stimulus that launches reactions at the molecular level and in the body in general. Increased MPOD further protects the retina from the damaging effects of free radicals and phototoxic blue light, normalizes the redox processes in the macula delaying further AMD development.

Conclusions

  • Statistically significant increase in macular pigment optical density from 0.249±0.011 units to 0.388±0.016, by 0.139±0.014 units (by 55.8%) was noted in patients who underwent two courses of low-energy light therapy in combination with a course of conservative treatment. Macular pigment optical density index did not change in the patients in the control group.

  • Two courses of low-energy light therapy in combination with a course of conservative treatment increases the concentration of macular pigment, as evidenced by the increase in indices of macular pigment optical density in comparison with conservative treatment, during which indices stabilize.

References

1 

LV Wenher. Efektyvnist fotostymulyatsiyi monokhromatychnum impulsnym svitlom u vidnovnomu likuvanni khvorykh na ambliopiiu. Odeskyi med zhurnal. 2001;3:82-86.

2 

OV Guzun. Efektivnost nizkointensivnogo lazernogo izlucheniya v lechenii bolnykh sukhoi formoi tsentralnoi ateroskleroticheskoi khorioretalnoi distrofii. PhD Thesis. 2002. 163 p..

3 

MI Kulyakin, VT Paramei, EI Klyutsevaya, IG Savostenko. Svetoterapiya vysokoi oslozhnennoi blizorukosti. Oftalmol zhurnal. 1981;1:228-231.

4 

MI Kulyakin, VT Paramei, EI Klyutsevaya, IG Savostenko. Fototerapiyachastichnoi atrofii zritelnoho nerva. Oftalmol zhurnal. 1982;3:159-162.

5 

ES Leonova, EV Shchekotov, IV Kolina. Znachenie metodiki opredeleniya urovnya plotnosti optecheskogo pigmenta makuly v sokhranenii professionalnogo dolgoletiya rabotnikov zheleznodorozhnogo transporta. Problemy standartizatsiyu v zdravokhraneniyi. 2010;5-6:55-60.

6 

NF Leus, IL Metelitsyna, LA Linnik. Deistvie nizkoenergeticheskikh izlucheniy geliy-neohovogo lazera na gidrolitichesnie fermenty lizoom setchatoi obolochi glaza. Oftalmol zh. 1989;2:6-11.

7 

LA Linnik, NI Usov, IL Baronetskaya. Stimulyatsia funktsionalnoi aktivnosti tkanei glaza lazernym izlucheniem. In: Tezisy dokladov V siezda oftalmologov SSSR. Tom 3. Moscow; 1979. p. 126-127.

8 

TE Marchenkova, EM Mironova, KV Golubtsov, MV Arnoldov. Ispolzovanie khromaticheskoi impulsnoi foto stimuliatsii dlia lecheniya patologiyi setchatki i zritelnogo nerva. Oftalmol zh. 2006;3 (ΙΙ):27-30.

9 

EM Mironova, DA Magaramov, ON Pavlova, LM Futoryan. Vliyanie lazer stimuliatsii na funktsionalnoe sostoyanie pigmentnogo epitaliya setchatki. Oftalmokhirurgiya. 1991;2:57-58.

10 

TV Monoylo, ZV Gubrik, II Deynichenko. Opticheskaya plotnost makulyarnogo pigmenta v zdorovoi populyatsii. Problemy, dostizheniya i perspektivy razvitiya medico-biologicheskikh nauk. 2010;146:206.

11 

NV Pasechnikova.Lazernoe sechenie pri patologii glaznogo dna. Kyiv: Naukova dumka; 2007. 206 p.

12 

AM Soldatova. Rol svobodnoradikalnykh, okislitelno-vosstanovitelnykh protsessov i vidimogo sveta v patogeneze skleroticheskoi makulodistrofii i ee differentsirovannoe lechenie. Extended abstract of MD Thesis. Odessa; 1992. 36 p.

13 

Age-Related Eye Disease Study Research Group. A randomized placebo-controlled clinical trial of high-dose supplementation with vitamins C and E, beta-carotene and zinc for age-related macular degeneration and vision loss. Arch Ophthalmol. 2001;119:1417-1436. doi:10.1001/archopht.119.10.1417

14 

Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-relatrd macular degeneration: the Age-Related Eye Disease Study 2 (AREDS 2) randomizedclinical trial. JAMA. 2013;309(19):2005-2015. doi:10.1001/jama.2013.4997

15 

GA Armstrong, JE Hearst. Genetics and molecular biology of carotenoid pigment biosynthesis. FASEB J. 1996;10(2):228-237.

16 

S Beatty, IJ Murray, DB Henson, D Carden, H Koh, ME Boulton, et al. Macular pigment and risk for age-related macular degeneration in subjecrsfrom a Northen European population. Invest Ophthalmol Vis Sci. 2001;42:439-446.

17 

TT Berendscot, JJ Willemse-Assink, M Bastiaance, Jong PT de, Norren D van. Macular pigment and melanin in age-related maculopathy in a general population. Invest Ophthalmol Vis Sci. 2002;43:1928-1932.

18 

PS Bernstein, D-Y Zhao, SW Wintch, IV Ermakov, RW McClane, W Gellermann. Resonance Raman measurement of macular carotenoids in normal subjects and in age-related macular degeneration patients. Ophthalmology. 2002 Oct;109(10):1780–1787. doi:10.1016/S0161-6420(02)01173-9

19 

C Delcourt, I Carrie`re, M Delage, P Barberger-Gateau, W Schalch. Plasma Lutein and Zeaxanthin and Other Carotenoids as Modifiable Risk Factors for Age-Related Maculopathy and Cataract: The POLA Study. Investig Opthalmology Vis Sci. 2006 Jun 1;47(6):2329. doi:10.1167/iovs.05-1235

20 

C Delcourt. Light Exposure and the Risk of Age-Related Macular Degeneration. Arch Ophthalmol. 2001 Oct 1;119(10):1463. doi:10.1001/archopht.119.10.1463

21 

J Dennison, S Beatty, GO Regan, J Nolan. Impact of macular pigment on visual performance. Actual optometry. 2013;2:28-33.

22 

R Klein, T Peto, A Bird, MR Vannewkirk. The epidemiology of age-related macular degeneration. Am J Ophthalmol. 2004 Mar;137(3):486–95. doi:10.1016/j.ajo.2003.11.069

23 

J Loughman, PA Davison, JM Nolan, MC Akkali, S Beatty. Macular pigment and its contribution to visual performance and experience. J Optom. 2010 Apr;3(2):74–90. doi:10.1016/S1888-4296(10)70011-X

24 

SM Moeller. Associations Between Intermediate Age-Related Macular Degeneration and Lutein and Zeaxanthin in the Carotenoids in Age-Related Eye Disease Study (CAREDS). Arch Ophthalmol. 2006 Aug 1;124(8):1151. doi:10.1001/archopht.124.8.1151

25 

K Neelam, RE Hogg, MR Stevenson, E Johnston, R Anderson, S Beatty, et al. Carotenoids and Co-Antioxidants in Age-Related Maculopathy: Design and Methods. Ophthalmic Epidemiol. 2008 Jan 8;15(6):389–401. doi:10.1080/09286580802154275

26 

JM Nolan, MC Akkali, J Loughman, AN Howard, S Beatty. Macular carotenoid supplementation in subjects with atypical spatial profiles of macular pigment. Exp Eye Res. 2012 Aug;101:9–15. doi:10.1016/j.exer.2012.05.006

27 

JM Nolan, J Loughman, MC Akkali, J Stack, G Scanlon, P Davison, et al. The impact of macular pigment augmentation on visual performance in normal subjects: COMPASS. Vision Res. 2011 Mar;51(5):459–469. doi:10.1016/j.visres.2010.12.016

28 

JM Nolan, J Stack, O O’Donovan, E Loane, S Beatty. Risk factors for age-related maculopathy are associated with a relative lack of macular pigment. Exp Eye Res. 2007 Jan;84(1):61–74. doi:10.1016/j.exer.2006.08.016

29 

O Sommerburg, WG Siems, JS Hurst, JW Lewis, DS Kliger, Kuijk FJGM van. Lutein and zeaxanthin are associated with photoreceptors in the human retina. Curr Eye Res. 1999 Jan 2;19(6):491–495. doi:10.1076/ceyr.19.6.491.5276

30 

JM Stringham, BR Hammond. The Glare Hypothesis of Macular Pigment Function. Optom Vis Sci. 2007 Sep;84(9):859–864. doi:10.1097/OPX.0b013e3181559c2b

31 

M Trieschmann, S Beatty, JM Nolan, HW Hense, B Heimes, U Austermann, et al. Changes in macular pigment optical density and serum concentrations of its constituent carotenoids following supplemental lutein and zeaxanthin: The LUNA study. Exp Eye Res. 2007 Apr;84(4):718–728. doi:10.1016/j.exer.2006.12.010

32 

G Weigert, S Kaya, B Pemp, S Sacu, M Lasta, RM Werkmeister, et al. Effects of Lutein Supplementation on Macular Pigment Optical Density and Visual Acuity in Patients with Age-Related Macular Degeneration. Investig Opthalmology Vis Sci. 2011 Oct 17;52(11):8174. doi:10.1167/iovs.11-7522

33 

WL Wong, X Su, X Li, CMG Cheung, R Klein, C-Y Cheng, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Heal. 2014 Feb;2(2):e106–116. doi:10.1016/S2214-109X(13)70145-1



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