mercury ( hg ) is a hazardous environmental and industrial pollutant that induces severe alterations in the body tissues of both humans and animals . it exists in several forms : inorganic mercury , which includes metallic mercury , mercury vapor , and mercurous or mercuric salts ; and organic mercury , which includes compounds in which mercury is bonded to a structure containing carbon atoms ( methyl , ethyl , phenyl , or similar groups ) . human mercury exposures occur chiefly through inhalation of elemental mercury vapor via occupational or dental amalgam exposure , or through ingestion of mercury bonded to organic moieties ( methyl , dimethyl , or ethyl mercury ) , primarily from seafood . inhaled elemental mercury vapor is especially easily absorbed through mucus membranes and the lung and is then transported to the rest of the body via the blood . it accumulates in the brain , thyroid , breasts , myocardium , liver , kidneys , and eyes , and may be associated with dysfunction of those organs . in recent studies it has been shown that mercury accumulates in the lens , optic nerve , optic disc , retina pigment epithelium , and retina . ocular findings in patients with chronic exposure to mercury are : discoloration of the cornea and lens , tremor of the eyelids , disturbances of vision and of extraocular muscles , and in very young children a special manifestation of acrodynia that includes photophobia , conjunctivitis , and keratitis   can be found . in addition , chronic exposure to mercury may result in peripheral vision loss , followed by a more severe central vision loss . in the medical literature there is no study investigating the toxic effects of mercury on the ocular system by using spectral - domain optical coherence tomography ( sd - oct ) . therefore , this review was written to focus on the use of sd - oct to evaluate the toxic effects of mercury on retinal nerve fiber layer thickness ( rnflt ) , macular thickness ( mt ) , and choroidal thickness ( ct ) in battery industry workers who had been chronically exposed to mercury . the study adhered to the tenets of the declaration of helsinki and was approved by the local ethics committee ( meeting : 03.01.2011 ; document no . battery factory workers ( n=31 ) and healthy non - factory employee control subjects ( n=15 ) participated in the study . participants were divided into 3 groups : group 1 ( n=15 ) was factory workers who had worked for more than 5 years in a mercury battery factory ; group 2 ( n=16 ) was factory workers who had worked for less than 5 years in a mercury battery factory ; and group 3 ( n=15 ) was healthy non - employees collected from patients who had been seen in our clinic . at the beginning of the study , factory workers were interviewed about physical complaints possibly resulting from mercury exposure , which included : dyspnea , gingivitis , involuntary tremor in the eyelids - face - fingers and hands , anxiety , attention difficulties , forgetfulness , insomnia , fatigue , and headache . individuals who were using drugs , vitamins , cigarettes , or alcohol were excluded from the study , as were those who had ( or whose family members had ) diabetes , hypertension , or ophthalmological pathologies . the control group was composed of a random selection of patients who had been seen at our clinic and who had lived in istanbul for at least 5 years . all participants were given a best - corrected visual acuity ( bcva ) test , color vision test , full ophthalmologic examination , and sd - oct of rnlf , macula , and choroid . these tests were performed in the routine facilities of the institute and the technicians administering the test were unaware of the diagnosis or employment history of the patients . color vision scores ( cvs ) were determined using farnsworth - munsell ( fm ) 100 testing , which was performed in a dark room with test materials viewed under standard light conditions . subjects used near vision correction , if needed , and were given 2 min to complete each of the 4 test boxes . total error score was calculated according to the manufacturer s recommendations , and the square root of the total error score was used in analyses . a high value reflects a defect of color vision . for the purpose of statistical analysis , snellen chart visual acuity was converted to the logarithm of the minimal angle of resolution ( log mar ) value . to determine mercury exposure , sd - oct was performed through undilated pupils using rtvue version 4.0 ( optovue corp . , fremont , ca ) by the same 2 investigators . only scans that reached signal strengths of 6 , which indicates a high - quality scan , were accepted for analyses . the rnfl scan pattern completes circular scans in 0.15 s at a diameter of 3.45 mm , targeted around the optic nerve head . the instrument makes use of a retinal cross - line scanning pattern that includes a 1024 a scan , and consists of two 6-mm orthogonal lines . with an automatic reversal of the image , the retinal cross - line scanning method consists of the mean of 32 patterns in 16 directions , with no eye tracking . after measuring the peripapillary rnflt , measurement of mt was performed in a 1-mm diameter circle within the central macula ( fovea ) for all measurements . the rtvue-100 has a 5 mm axial image resolution , with an imaging speed of 26 000 axial scans per second . cts were measured perpendicularly from the outer edge of the retinal pigment epithelium ( rpe ) to the choroid - sclera boundary at the fovea itself , 500 and 1000 mm nasal to the fovea , and 500 and 1000 mm temporal to the fovea . differences between readings of the masked physicians were determined to be within 10% of the mean . venous blood samples for mercury analyses were collected from the battery factory workers and healthy non - employees . the samples were analyzed for mercury content by a modified method described by einarson et al . . briefly , samples were digested with a mixture of hclo4 and hno3 overnight at 68c . version 11.5 spss ( spss inc . , chicago , il ) software was used for statistical analyses . the mann - whitney u - test was applied for post - hoc comparisons ( least significant difference [ lsd ] ) . the study adhered to the tenets of the declaration of helsinki and was approved by the local ethics committee ( meeting : 03.01.2011 ; document no . battery factory workers ( n=31 ) and healthy non - factory employee control subjects ( n=15 ) participated in the study . participants were divided into 3 groups : group 1 ( n=15 ) was factory workers who had worked for more than 5 years in a mercury battery factory ; group 2 ( n=16 ) was factory workers who had worked for less than 5 years in a mercury battery factory ; and group 3 ( n=15 ) was healthy non - employees collected from patients who had been seen in our clinic . at the beginning of the study , factory workers were interviewed about physical complaints possibly resulting from mercury exposure , which included : dyspnea , gingivitis , involuntary tremor in the eyelids - face - fingers and hands , anxiety , attention difficulties , forgetfulness , insomnia , fatigue , and headache . individuals who were using drugs , vitamins , cigarettes , or alcohol were excluded from the study , as were those who had ( or whose family members had ) diabetes , hypertension , or ophthalmological pathologies . the control group was composed of a random selection of patients who had been seen at our clinic and who had lived in istanbul for at least 5 years . all participants were given a best - corrected visual acuity ( bcva ) test , color vision test , full ophthalmologic examination , and sd - oct of rnlf , macula , and choroid . these tests were performed in the routine facilities of the institute and the technicians administering the test were unaware of the diagnosis or employment history of the patients . color vision scores ( cvs ) were determined using farnsworth - munsell ( fm ) 100 testing , which was performed in a dark room with test materials viewed under standard light conditions . subjects used near vision correction , if needed , and were given 2 min to complete each of the 4 test boxes . total error score was calculated according to the manufacturer s recommendations , and the square root of the total error score was used in analyses . a high value reflects a defect of color vision . for the purpose of statistical analysis , snellen chart visual acuity was converted to the logarithm of the minimal angle of resolution ( log mar ) value . to determine mercury exposure , sd - oct was performed through undilated pupils using rtvue version 4.0 ( optovue corp . , fremont , ca ) by the same 2 investigators . only scans that reached signal strengths of 6 , which indicates a high - quality scan , were accepted for analyses . the rnfl scan pattern completes circular scans in 0.15 s at a diameter of 3.45 mm , targeted around the optic nerve head . the instrument makes use of a retinal cross - line scanning pattern that includes a 1024 a scan , and consists of two 6-mm orthogonal lines . with an automatic reversal of the image , the retinal cross - line scanning method consists of the mean of 32 patterns in 16 directions , with no eye tracking . after measuring the peripapillary rnflt , measurement of mt was performed in a 1-mm diameter circle within the central macula ( fovea ) for all measurements . the rtvue-100 has a 5 mm axial image resolution , with an imaging speed of 26 000 axial scans per second cts were measured perpendicularly from the outer edge of the retinal pigment epithelium ( rpe ) to the choroid - sclera boundary at the fovea itself , 500 and 1000 mm nasal to the fovea , and 500 and 1000 mm temporal to the fovea . differences between readings of the masked physicians were determined to be within 10% of the mean . venous blood samples for mercury analyses were collected from the battery factory workers and healthy non - employees . the samples were analyzed for mercury content by a modified method described by einarson et al . . briefly , samples were digested with a mixture of hclo4 and hno3 overnight at 68c . version 11.5 spss ( spss inc . , chicago , il ) software was used for statistical analyses . the mann - whitney u - test was applied for post - hoc comparisons ( least significant difference [ lsd ] ) . ophthalmological examination revealed no conjunctival , corneal , lenticular , or retinal abnormalities in any participant . median ages ( min - max ) of subjects in groups 13 were 21.90 ( 2436 ) , 23.13 ( 2433 ) , and 25.50 ( 2135 ) years , respectively . there were no statistically significant differences in ages between groups ( x=0.566 , p=0.754 ) . for all groups , bcva ( logmar ) , cvs , blood mercury level ( bml ) ( gr/100 ml ) , duration of mercury exposure ( months ) , oct values of rnflts , mts , and cts ( m ) are shown in table 2 . there were no statistically significant differences between group 1 and group 2 ( p=0.216 ) , but there were statistically significant differences between group 3 and both group 1 and group 2 with respect to bcva values ( 1=2<3 ) ( p=0.000 ) , color vision scores ( cvs ) , blood mercury levels ( bml ) , and duration ( mean sd , range ) of mercury exposure ( 1>2>3 ) ( p=0.000 ) . oct values of rnflts , mts , and cts of all 3 groups were significantly different from each another ( 1<2<3 ) ( p=0.000 ) ( figure 1 ) . in addition , when the correlation analysis was performed , a negative correlation between bml and bcva , cvs , rnflt , mt , and ct was observed ( table 3 ) . our study demonstrates that there was a negative correlation between bml and bcva , cvs , rnlfts , mts , and cts . to the best of our knowledge , ours is the first study that investigated the relationships between bml and oct findings . due to the absence of myelin sheath in retinal cell axons , the investigation of rnfl thickness by oct allows visualizing the processes of neuroaxonal degeneration in different central nervous system disorders . in the literature there are some studies investigating the neuroaxonal degeneration by using oct in schizophrenia , parkinson disease , and alzheimer disease [ 1214 ] . mercury is a hazardous environmental and industrial pollutant that has no known physiologic role in human metabolism and induces severe alterations in the body tissues of both humans and animals . mercury has a high affinity for sulfhydryl groups , various enzymes and amino acids , n - acetyl cysteine ( nac ) , alpha lipoic acid ( ala ) , and glutathione ( gsh ) , which provide about 1050% of plasma protein antioxidant capacity . it obstructs neurotransmission by acting as a strong competitive inhibitor of muscarinic cholinergic receptors ; inhibits the uptake of synaptic glutamate in neurons of the brain , resulting in an excitotoxic elevation of glutamate in the extracellular space and associated neuronal damage ; induces mitochondrial dysfunction and oxidative stress ; induces oxidative stress and cell cytotoxicity ; and increases the secretion of amyloid , which may lead to neurodegenerative diseases such as alzheimer and parkinson diseases . the major sources of mercury load in humans are food contamination , drug and vaccine preservatives , dental amalgams , and occupational exposure . following mercury exposure , decreased visual contrast sensitivity , impairment of scotopic ( night ) vision , reduced color vision and visual acuity , and in in vivo studies in laboratory animals vision loss   have been reported . have reported visual disturbance , recurrent attacks of visual loss , visual field defects , absent or blunted corneal sensations , iris atrophy , and pallor of the optic disk in their patients after organomercury poisoning . in our study , we observed no significant significances between group 1 and group 2 , but there was a statistically difference between group 3 and both group1 and group 2 with respect to bcva values ( 1=2<3 ) . for cvs values , we observed significant differences between all groups ( 1>2>3 ) . although feitosa - santana et al .   and ventura et al . observed color vision loss in both chromatic systems ( blue - yellow and red - green ) in patients with chronic mercury vapor intoxication , jedrejko et al .   and cavalleri et al . reported that the most observed color vision deficit was in blue - yellow range in workers exposed to elemental mercury vapor . in our study , the most observed color vision loss was in blue - yellow range , similar to results in the literature . accumulation of mercury in ocular tissues and ocular pathways may provoke anatomical and functional injuries to the eye . after exposure to mercury , findings in the cornea , including loss of epithelium , necrosis of keratocytes , absence of inflammatory reaction , endothelial cellular swelling , endothelial increased vacuolization , and diminished intercellular junctions , can be observed . in a study by kairada , active accumulation of mercury in the lens was observed after exposure to mercury . in their experimental study , khavat and dencker found mercury in the receptor layers , pigment epithelium , and choroid in mice immediately killed after exposure . additionally , warfvinge et al .   observed mercury in choroidal and retinal pigment epithelium , in ganglion cell layers , and in the optic disc layer and optic nerve in squirrel monkeys after mercury exposure . .   demonstrated that mercury decreases the number of nmda receptors in several brain regions , including the basal ganglia , cerebellum , brainstem , and occipital cortex of mink . in addition , sabelash et al . , in postmortem examination of a baby exposed to mercury and who was blind before death , observed the accumulation of mercury in the occipital lobe . according to the above - mentioned studies , it can be concluded that mercury has a toxic effect in the retinal photoreceptor layer , ganglion cell layer , optic disc , and optic nerve layer , and in the visual cortex layer . in our study , we found a negative correlation between bml and rnlfts values . however , warfvinge et al .   reported in their experimental study on neural retinas that they did not find mercury in the retina of the squirrel monkey eyes after mercury vapor exposure . in another study , they declared that the photoreceptor layer contained no visualized mercury except in the foveal region in the squirrel monkey retina after in utero exposure to mercury vapor . in our study the values of mts of all 3 groups were statistically different from each other ( 1<2<3 ) . it can be speculated that if there is no mercury accumulation in the fovea , the mts loss could be due to optic disc and optic nerve vasculitis , which occur after mercury exposure . however , warfvinge et al .   reported that after mercury exposure they did not observe mercury in choroidal vessel walls . in the literature there are associations between mercury toxicity and increased platelet aggregation , increased factor viii , reduced platelet endothelial cell formation and migration , decreased vascular endothelial repair , and decreased nitric oxide . additionally , the association between mercury toxicity and hypertension is well known [ 3840 ] . it has been shown that choroidal blood flow is regulated by parasympathetic innervation , with fibers rich in the vasodilator s vasoactive intestinal polypeptide ( vip ) and no . it has also been found that untreated systemic hypertension is associated with choroidopathy . under conditions such as decreased nitric oxide level and increased vasculopathy and choroidopathy , choroidal thickening may be an expected result . in our study , we observed a negative correlation between bml and cts values . the values of cts of all 3 groups were significantly different from each other ( 1<2<3 ) . in our study , bml of the healthy non - factory employees was detected as 1.671.18 gr/100 ml . in our opinion this is due to industrial fossil fuel emissions and atmospheric mercury , including coal burning , which are responsible for mercury exposure , especially in industrial and crowded cities . the weaknesses of our study include the facts that ( i ) the number of subjects was small , ( ii ) the visual field examination could not performed , ( iii ) urine should be collected over a 24-h period , and mercury levels were examined in urine instead of serum . it has been reported that urine samples are better for diagnosis of chronic intoxication   because of the short half - life of mercury in the blood , and ( iv ) we did not rule out the factors that may impair color vision , including chronic alcoholism , prolonged use of medicines ( e.g. , chloroquine ) , tuberculosis ( e.g. , ethambutol ) , and epilepsy ( e.g. , vigabatrin ) . we confirmed that chronic exposure to mercury has toxic effects on the retina , optic nerve neuronal fibers , and choroidal vasculature . in our opinion the reduced visual acuity is related to the accumulation and toxic effects of mercury in macula , retinal pigment epithelium , ganglion cell layers , and optic nerve neuronal fibers . mercury toxicity should be considered as a problem of public health concern , and the harmful effects can be confirmed by sd - oct . further sd - oct studies with larger numbers of subjects are necessary to confirm mercury toxicity in the rnfl , macula , and choroid .
backgroundthe aim of this study was to evaluate the toxic effects of mercury on retinal nerve fiber layer thickness ( rnflt ) , macular thickness ( mt ) , and choroidal thickness ( ct ) by using spectral - domain optical coherence tomography ( sd - oct ) in battery industry workers who had been chronically exposed to mercury.material/methodsbattery factory workers ( n=31 ) and healthy non - factory employee controls ( n=15 ) participated in the study . 
 participants were divided into 3 groups : group 1 ( n=15 ) was factory workers who had worked for more than 5 years in a mercury battery factory ; group 2 ( n=16 ) was factory worker who had worked for less than 5 years in a mercury battery factory ; and group 3 ( n=15 ) was healthy non - employees . 
 systemic symptoms were recorded . 
 ophthalmic examination included best - corrected visual acuity test , color vision test , full ophthalmologic examination , and sd - oct of the rnlf , macula , and choroid . to determine mercury exposure , 
 venous blood samples were collected and mercury levels were assessed.resultsin our study group the most common systemic symptoms were insomnia ( 67.7% ) and fatigue ( 67.7% ) . 
 there were no significant differences between group 1 and group 2 , but there were significant differences between group 3 and both group 1 and group 2 in best - corrected visual acuity values ( 1=2<3 ) , color vision scores , blood mercury levels , and duration ( mean sd , range ) of mercury exposure(1>2>3 ) . 
 oct values of rnflts , mts , and cts of all 3 groups were statistically different from each another ( 1<2<3).conclusionssd - oct can be useful for evaluating the toxic effects of chronic exposure to mercury .