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Year : 2012  |  Volume : 15  |  Issue : 4  |  Page : 350-351

Long sleep duration and frequent day-time naps of the infants can be protective for vigabatrin-induced visual field defects

1 Department of Pediatric Neurology, Istanbul Medical Faculty, Fatih/Istanbul, Turkey
2 Department of Ophthalmology, Cerrahpasa Medical Faculty, Fatih/Istanbul, Turkey

Date of Web Publication5-Dec-2012

Correspondence Address:
Baris Ekici
Ortaköy Dereboyu cad, Arkeon sitesi A 5 blok D 3, Besiktas/Istanbul
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0972-2327.104359

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How to cite this article:
Ekici B, Yildirim Y, Ucar D, Tatli B. Long sleep duration and frequent day-time naps of the infants can be protective for vigabatrin-induced visual field defects. Ann Indian Acad Neurol 2012;15:350-1

How to cite this URL:
Ekici B, Yildirim Y, Ucar D, Tatli B. Long sleep duration and frequent day-time naps of the infants can be protective for vigabatrin-induced visual field defects. Ann Indian Acad Neurol [serial online] 2012 [cited 2021 Feb 25];15:350-1. Available from:


Vigabatrin (VGB) is used for the adjunctive treatment of refractory partial epilepsy and for initial monotherapy of infantile spasm because of its action that inhibits GABA transaminase leading to increased levels of inhibitory neurotransmitter GABA in presynaptic nerve terminals. [1] One of the important concerns that limit its use is irreversible visual field defects. Incidence of visual field defects is reported in up to 40% of adult patients but is lower in pediatric patients at 19-22%. [2],[3],[4] Also, a recent study stated that the risk of visual field defects may be lower in children who are treated with VGB in infancy compared with patients who receive VGB at a later age. [5]

Retinal toxicity of VGB was first described in albino rats. [6] VGB can accumulate in retina and concentrations can reach as much as five-fold higher than in the brain. [7] It was shown that the most obvious retinal change was disorganization of the peripheral retinal photoreceptor layer. [8] It was suggested that VGB mediates phototoxicity, as it was found that retinal explants exposed to light of strong intensity showed photoreceptor degeneration in the presence of VGB. Solely, high GABA concentrations did not cause acute retinotoxicity, even in the presence of strong light. It was suggested that brief VGB exposure damages the outer retina by sensitizing photoreceptors to light-induced damage and this phototoxic damage also involves reactive oxygen species. [9]

Melatonin is a hormone synthesized by the pineal gland and retinal photoreceptors under a cyclic rhythm with peak levels occurring during night period. [10] Melatonin synthesized by photoreceptors is thought to act as a paracrine neurohormone with local effects in the retina. [11] Melatonin is involved in photoreceptor outer segment disc where they perform shedding, phagocytosis, and delays photoreceptor degeneration. [12] It is an efficient direct scavenger of the highly toxic hydroxyl radical and also reduces oxidative damage by activating enzymes of anti-oxidative defense system including superoxide dismutase, catalase, and glutathione peroxidase. [13],[14] Paradoxically, inappropriate (i.e., daytime) exposure of retinal cells to melatonin may be detrimental to photoreceptor cell survival, as supported by reports that melatonin increases the degree of light-induced photoreceptor cell death. Chronic melatonin exposure of the retina at inappropriate times of day and lighting conditions may increase the risk of susceptibility of photoreceptors to damage by environmental illumination. [15],[16] The highest melatonin levels are found in children younger than 4 years old with longer sleep durations and frequent day-time naps. [17] Zhdanova et al. compared two doses of melatonin in 12 volunteers to evaluate its effect on sleep and reported that administration of 0.3 mg melatonin elevated serum melatonin to levels within the normal nocturnal range. This dose neither caused any side effects on mood and performance nor altered sleep architecture significantly in subjects with normal sleep. [18]

Hypothesis: Despite the fact that immature and developing nervous system of children has much more plasticity, is more prone to toxic insults and longer treatment durations and higher total doses needed, VGB retinotoxicity is less common than adults. The hypothesis we propose here is that the possible explanation of this is high melatonin levels, longer sleep durations, and frequent day-time naps of infants. This physiological status protects retinal cells of infants from oxidative stress and exposure to intense light, which concurrently protects from the VGB-induced visual field defects. We also think that low oral doses of melatonin given to adult patients several hours before habitual bedtime may prevent VGB-related visual field defects.

   References Top

1.Petroff OA, Rothman DL, Behar KL, Collins TL, Mattson RH. Human brain GABA levels rise rapidly after initiation of vigabatrin therapy. Neurology 1996;47:1567-71.  Back to cited text no. 1
2.Kälviäinen R, Nousiainen I. Visual field defects with vigabatrin: Epidemiology and therapeutic implications.CNS Drugs 2001;15:217-30.  Back to cited text no. 2
3.Vanhatalo S, Nousiainen I, Eriksson K, Rantala H, Vainionpää L, Mustonen K, et al. Visual field constriction in 91 Finnish children treated with vigabatrin. Epilepsia 2002;43:748-56.  Back to cited text no. 3
4.You SJ, Ahn H, Ko TS. Vigabatrin and visual field defects in pediatric epilepsy patients. J Korean Med Sci 2006;21:728-32.  Back to cited text no. 4
5.Gaily E, Jonsson H, Lappi M. Visual fields at school-age in children treated with vigabatrin in infancy. Epilepsia 2009;50:206-16.  Back to cited text no. 5
6.Butler WH, Ford GP, Newberne JW. A study of the effects of vigabatrin on the central nervous system and retina of Sprague Dawley and Lister-Hooded rats. Toxicol Pathol 1987;15:143-8.  Back to cited text no. 6
7.Sills GJ, Patsalos PN, Butler E, Forrest G, Ratnaraj N, Brodie MJ. Visual field constriction: Accumulation of vigabatrin but not tiagabine in the retina. Neurology 2001;57:196-200.  Back to cited text no. 7
8.Duboc A, Hanoteau N, Simonutti M, Rudolf G, Nehlig A, Sahel JA, et al. Vigabatrin, the GABA-transaminase inhibitor, damages cone photoreceptors in rats. Ann Neurol 2004;55:695-705.  Back to cited text no. 8
9.Izumi Y, Ishikawa M, Benz AM, Izumi M, Zorumski CF, Thio LL. Acute vigabatrin retinotoxicity in albino rats depends on light but not GABA. Epilepsia 2004;45:1043-8.  Back to cited text no. 9
10.Wiechmann AF, Bok D, Horwitz J. Melatonin binding in the frog retina:autoradiographic and biochemical analysis. Invest Ophthalmol Vis Sci 1986;27:153-63.  Back to cited text no. 10
11.Wiechmann AF. Melatonin: Parallels in pineal gland and retina. Exp Eye Res 1986;42:507.  Back to cited text no. 11
12.White MP, Fisher LJ. Effects of exogenous melatonin on circadian disc shedding in the albino rat retina. Vision Res 1989;29:167.  Back to cited text no. 12
13.Poeggeler B, Saarela S, Reiter RJ, Tan DX, Chen LD, et al. Melatonin--a highly potent endogenous radical scavenger and electron donor: new aspects of the oxidation chemistry of this indole accessed in vitro. Ann N Y Acad Sci. 1994; 738: 419-20  Back to cited text no. 13
14.Antolin I, Rodriguez C, Sainz RM, Mayo JC, Uría H, Kotler ML, et al. Neurohormone melatonin prevents cell damage effect on gene expression for antioxidant enzymes. FASEB J 1996;10:882-90.  Back to cited text no. 14
15.Wiechmann AF, O'steen WK. Melatonin increases photoreceptor susceptibility to light-induced damage. Invest Ophthalmol Vis Sci 1992;33:1894-902.  Back to cited text no. 15
16.Wiechmann AF, Chignell CF, Roberts JE. Influence of dietary melatonin on photoreceptor survival in the rat retina: An ocular toxicity study. Exp Eye Res 2008;86:241-50.  Back to cited text no. 16
17.Touitou Y. Human aging and melatonin. Clinical relevance. Exp Gerontol 2001;36:1083-100.  Back to cited text no. 17
18.Zhdanova IV, Wurtman RJ, Morabito C, Piotrovska VR, Lynch HJ. Effects of low oral doses of melatonin,given 2-4 hours before habitual bedtime, on sleep in normal young humans. Sleep 1996;19:423-31.  Back to cited text no. 18


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