The Eyes - a neglected organ in Environmental and Occupational Medicine. An Overviw of the known ENVIRONMENTAL AND OCCUPATION non-traumatic EFFECTS ON THE EYES
The objective of this study was to give an overview of the known literature data on the influence of environmental and occupational factors on the eye. Fifty nine articles were selected by searching Medline and PubMed databases by the following key words in different combinations: occupational and environmental factors, dry eye syndrome, cataract, retinal vascular changes.
It was noticed that most of the studies dealt with the conditions of the ocular surface and used discomfort eye syndrome and dry eye syndrome to outline the effects of air pollutants. The increased frequency of lens opacities due to indoor fuel exposure, in particular biofuel, and negative affect of styrene exposure on color vision were reported. Retinal vascular changes and retinopathy after chronic exposure to carbon disulfide (CS2) and retinal and choroidal hemodynamics after exposure to carbon monoxide (CO) were investigated. It was found that CS2 caused an increase in retinal venous diameters and CO caused the increase in arterial and venous diameters, retinal blood flow velocity, and fundus pulsation amplitude. The influence of light exposure on the retinal damage was discussed. This literature survey shows that very little information is available regarding the influence of environmental and occupational factors on the eye, in particular on retina and retinal vessels.
Key words: Occupational and environmental factors, Dry eye syndrome, Cataract, Retinal vascular changes
The eye is the most important organ needed for human activities. Nevertheless, it has been neglected in occupational medicine. An intact vision is necessary for preventing occupational, traffic and non-occupational injuries. Unfortunately, very little effort has been put into the investigation of eye conditions during working life. In the general population an increase of dry kerato-conjunctivits (kerato-conjunctivitis Sicca), cataract and age-related macular degeneration has been observed. The question is: how do occupational factors contribute to the acceleration of the natural ageing processes of the eye, and do specific occupational hazards, in concentrations under the accepted threshold values, induce acute and chronic eye damage or disease. Furthermore, the question is whether we may prevent the ocular diseases of advanced age by introducing preventive measures during the working life - at work and at home.
Air pollution becomes ubiquitous. The occupational and environmental pollution is overlapping. It is implicated in different health conditions as well. Numerous epidemiological studies have demonstrated short term associations between high levels of air pollution and increased acute mortality and morbidity 1-5.
There is consistent evidence that increased levels of five major outdoor-air pollutants: particles of less than 10 µm in aerodynamic diameter (PM10), ozone (O3), carbon monoxide(CO), sulfur dioxide (SO2), and nitrogen mono- (NO) and dioxide (NO2) get release into the atmosphere and can be carried to long distances and thus inducing long range effects in living nature. They are as well associated with increased rates of mortality and morbidity in developed and developing countries 6. Nitrogen mono- and dioxide are primary pollutants which undergo various complex atmospheric reactions to generate secondary pollutants such as ozone which are known to cause severe adverse effects on human health. Transportation (combustion engiges) is apart from heating the major source of atmospheric NO 7.
It has been shown that short-term inhalation of fine particulate air pollution particles and ozone, at concentrations that occur in urban environment, causes acute conduit artery vasoconstriction 8. Relations between asthma, bronchitis, cardiovascular conditions (coronary disease) and outdoor pollution rates have so far been described 9-11. Nitrogen dioxide is known as a deep lung irritant. Significant correlation between incidents of asthma and levels of SO2, NO2, and PM10 has been demonstrated 12. Moreover, the association between carbon monoxide, NO2 and coronary events, hospitalizations and mortality, has been shown in large epidemiological studies 6,9.
It was reported that in the recent years, the variety and levels of pollutants in the atmosphere have increased, mainly due to the general rise in combustion processes - industry and vehicle traffic. Short term meteorological conditions such as air temperature, humidity, and atmospheric pressure have also been shown to influence the pollution rates.
A survey of the literature shows that in spite of the knowledge on increased pollution rates (by the mentioned 4 major pollutants) and reported increased ocular discomfort of the individuals, little information is available regarding the effects of air pollution on the eye, in particular on retina and retinal vessels, when compared to the effect of air pollution on pulmonary or cardio-vascular systems13. Some of these data investigating ocular effects come from experimental studies in which air pollutants were used on human volunteers or animals in arbitrary doses or in doses even higher than those ever expected during episodes of air pollution14,15.
The 59 references were selected by searching Medline and PubMed databases by the following key words in different combinations: occupational and environmental factors, dry eye syndrome, cataract, retinal vascular changes.
Concerning the direct effect of air pollution on the eye, most of the studies dealt with the conditions of the ocular surface and used eye irritation as the criterion for the effects of air pollutants16. Manifestations can range from minimal or no symptoms to chronic discomfort and eye irritation, 15,17 reduction of visibility, and increased light sensitivity 18.
The most common eye condition due to air pollution described in the literature is the discomfort eye syndrome (DES).
The National Eye Institute/Industry Workshop on Clinical Trials in Dry Eyes 19 defined dry eye as "a disorder of the tear film due to tear deficiency or excessive tear evaporation, which causes damage to the inter-palpebral ocular surface and is associated with symptoms of ocular discomfort".
DES comprises a series of 'minor' subjective symptoms in patients where no relevant clinical signs are observed suggesting ocular disease. Both epidemiological studies and controlled human exposure clinical studies have shown cause-effect relationships between ocular discomfort and various outdoor air pollutants levels as well as indoor irritants, which are known to cause the sick building syndrome (SBS). Ocular surface inflammation is thought to be responsible for pollution-induced DES, without allergy.
Versura and colleagues (1999) 20 performed a clinical study of 100 patients complaining on DES in both, winter and summer time. The Schirmer test I, ferning test, breakup time (BUT) and conjunctival cytology (scraping and imprint) were performed. These data were related to sex, age and air pollution indexes, recorded in the patients' living zones. The authors demonstrated that the ocular surface cytology and the analysis of tear film changes provided significant information in patients without evident clinical signs of an eye disease. DES symptoms were found to be more frequent in women than in men (ratio about 2:1), in subjects over 51 years of age. The authors concluded that DES is significantly associated with ocular surface inflammation, as detected by cytological methods, and ocular surface subclinical inflammation and ocular dryness are related to high concentrations of atmospheric polluters, in both sexes. Specifically affected are contact lens wearers, in whom the effect of air pollution seems to be more accentuated21.
DES, in general, is the most frequent disorder in ophthalmology practice 22. The prevalence of dry eyes varies from 10.8% to 57.1%, 23-25 depending on the study. Much of these disparity stands for poor standardization of patient selection for the study, non-standardized dry eye questionnaires, lack of objective tests and dry eye diagnostic criteria. The abnormality of the pre-ocular tear film is suggested to cause the DES. The pre-ocular tear film is a three-layered structure -consisting (from posterior to anterior) of the mucous, the aqueous and the lipid layer. Various risk factors accounting for DES listed in literature include air pollution, cigarette smoking, low humidity, high temperature, sunlight exposure and drugs 26-27.
The eye discomfort may be caused by pH changes of the lacrimal film. Andres et al. (1988) 28 determined that the influence of air pollution, specifically sulfur dioxide (SO2), on the tear pH of a random sample of 100 subjects, divided into 3 groups according to the stability of their precorneal tear film (normal eyes, borderline, and dry eyes). The average pH value obtained was 7.52. The pH for borderline and dry eyes was higher than for normal eyes. Authors found that air pollution affected the lacrimal pH, which decreased when the atmospheric SO2 increased.
Gupta SK. and colleagues (2002) 26 described the effects of air pollution on the eyes of persons residing in New Delhi. Tear film abnormalities were present in a large number of people staying within the city, in comparison to people living outside this area who have apparently normal eyes. Authors suggested that air pollution over a long period of time could possibly be associated with tear film abnormalities. In the study of Sahai and Malik (2005) 29dry eye prevalence increased progressively with age, and the age group 31-40 years showed a relative peak. Authors suggested that this peak reflects a dry eye state induced by environmental exposure, to which this age group, being the most active occupationally, is exceptionally prone. This phenomenon may be more common in tropical countries where sunlight and wind exposure is immense. Exposure to excessive wind, sunlight, high temperature, and drugs related significantly to dry eye causation. Most studies report a higher prevalence of dry eye in females than males. Menopause causes estrogen deficiency and a consequent change in the local hormonal milieu of the lacrimal gland. It is thought to decrease tear production and the occurrence of dry eye in females. Smoking predisposes the eye to tear film instability by its direct irritant action on the eyes and represents a modifiable risk factor in dry eye causation. A drug, also, may disrupt one or more components of the tear film causing it to become unstable.
It is postulated that persons with refractive errors have an increased tendency to rub their eyes and apart from the introduction of infective material, sebum and sweat, could cause the lodgment of particulate foreign substances into the eye that predispose to tear film instability. It was also demonstrated that dry eye was more prevalent in hypermetropes than in myopes and was least prevalent in emmetropes 27. It is also essential to realize that the dry eye prevalence is usually expected to be higher in contact lens users. Bourcier and colleagues (2003) 30 investigated the association between the number of ophthalmologic emergencies, urban air pollution, and climatic conditions in Paris to determine the possibility of creating a surveillance system capable of monitoring trends in the relation between air pollution and ophthalmologic emergencies. Five major urban air pollutants: nitrogen oxide, nitrogen dioxide, carbon monoxide, ozone, sulphur dioxide particles with a median aerodynamic diameter of <10 µm were examined and provided by the Paris air pollution network, AIRPARIF. Meteorological data for the Paris area were provided by the national weather service, Meteo-France and consisted of the daily minimum and maximum temperature, the daily minimum and maximum humidity, the mean daily atmospheric pressure, wind speed and strength. A total of 30 883 patients were examined during 1999 and 3042 diagnoses were recorded in the randomization process. Among these, 41.8% were categorized as conjunctivitis and related ocular surface problems. The relationship between conjunctivitis and related ocular surface problems, air pollution, and meteorological parameters was strong. The oxidative environmental pollutant NO2, as well as, the high temperature and instant wind strength, were associated with conjunctivitis and other ocular surface diseases. This study suggested that high levels of air pollution experienced in Paris are linked to short term increases in the number of people visiting ophthalmologic emergency department. Therefore, authors suggested that the results indicate a strong relationship between air NO, NO2 concentrations, and conjunctivitis. Changes in the lacrimal pH, such as those produced by the acidification of tears in an atmosphere with a high oxidant power (NO, NO2, SO2), could thus exert irritant effect on the ocular surface. Furthermore, authors found that atmospheric pressure, minimal humidity, and wind speed may have direct mechanical or biological effects on the ocular surface and could thus increase the incidence of ocular surface complaints. Authors hypothesized that the ophthalmic effects of air pollutants and allergenic pollens can be enhanced by hot weather conditions. On the other hand, other parameters such as low humidity, and wind strength may directly affect tear film stability. The occupational environment may be an additional burden to the eyes. Eye irritation is one of the most frequently reported symptoms in relation to working in office-like environments. Based on database searches , it was concluded that precorneal tear film (PTF) alteration leads to eye complaints that may be caused by thermal factors (low relative humidity; high room temperature), demanding task content (concentration decreases blinking and widens the exposed ocular surface area), and individual characteristics (for example, tear film alterations, blinking anomalies, gland dysfunction, use of contact lenses, eye make-up, and certain medication) 31. These factors and conditions progressively increase water evaporation and accelerate thinning of the PTF, which causes dryness and dry spot formation on the cornea, possibly followed by corneal and conjunctiva epithelial alterations and eye complaints. Other possible cause of eye complaints are certain irritating chemical compounds, in addition to oxidation mixtures formed in reactions between ozone and unsaturated organic compounds (alkenes). If airborne particles alone destabilize the tear film and cause eye irritation, their content of surface-active compounds must be high. The effect may be exacerbated by relative low humidity.
The not hitherto considered external physical factors could have a large influence on particle deposition velocity onto the ocular surface 32. This may have obscured the role of airborne particles. Based on previously published models, the paper describes the influence of turbulence, gravitational settling, electrical fields, and thermophoresis on deposition velocity. A probabilistic approach was used to determine percentile ranges in deposition velocity when the magnitude of these parameters varied within typical ranges. These calculations suggested that differences in external factors other than particle size may cause differences in deposition velocity onto the ocular surface.
Office workers frequently report eye problems, including dryness, burning, feeling of "sand" in the eyes or increased lacrimation. Brasche et al. (2005) 33 described profiles of factors affecting self-reported eye symptoms and objectively determined tear film characteristics using data from 814 office workers. Multiple logistic regression analysis reveals significantly increased risks of subjective perception of eye symptoms in female gender, in contact lens users and in persons with health problems. A reduced breakup time depends on personal criteria such as a history of eye disease and female gender. Age under 40 years, high relative humidity and formaldehyde exposure exceeding the 90th percentile are protective regarding BUT. For a thin lipid layer (an indication of dry eyes) significantly increased risks are detected for high particle load, high endotoxin concentration and female gender. Authors, therefore, concluded that there is a need for the development and application of objective clinical methods for field monitoring in parallel with questionnaires. Thus, self-reported eye symptoms in conjunction with indoor environmental problems should be validated by objective medical examinations such as semi-quantitative estimation of the superficial lipid layer, measurement of the breakup time or assessment of conjunctival epithelial damage. Individual physical and psychological factors such as acute illness or low job satisfaction should be additionally taken into account. Indoor and outdoor air pollution should be controlled, including as a minimum requirement measurements of particles, NO2, relative humidity, and endotoxin levels to detect environmental influences on eye symptoms.
In several studies changes in eye blink frequency were used as an indicator for sensory irritation due trigeminal stimulation by exposure to indoor pollutants. In the study of Kleno and Wolkoff (2004) 34 the mean blink frequency increased significantly during subjects' exposure to gas-phase oxidation products at lower part-per-billion (ppb) levels of limonene oxidation products (LOPs), and nitrate radicals (NO3), compared to controls. Neither the residual reactants nor clean air changed the blink frequency significantly. Authors concluded that changes in blink frequency appear to be a promising measure of trigeminal stimulation from exposure to eye irritants in ppb levels. Gaseous products of limonene and ozone may cause eye irritation indoors. In addition, Kiesswetter et al. (2005) 35, showed strong dose-response relationships between airborne solvent concentrations and blink rates. Authors showed that during 40 ppm peak exposures to 2-ethylhexanol the blink rate increased threefold. In the course of 4 hours exposure the blink rates increased significantly showing no adaptation. The results indicate that the irritative potential of 2-ethylhexanol is higher than generally expected. Authors suggested that electromyographic eye blink recordings were an objective, thus appropriate method for the examination of acute sensory irritations.
Kjaergaard and coworkers (2004) 36 performed a population study of eye trigeminal sensitivity, tear film stability, and conjunctival epithelium damage in 182 non-allergic, non-smoking Danes. The population distributions of CO2-induced irritation sensitivity in the eyes (COI), tear film stability (BUT), and epithelium damage (ED) and the relation of these parameters with an age- and gender-stratified random sample of citizens in Aarhus County, Denmark, was analyzed. The COI average for all levels was normally distributed and the total score for ED was deviated only marginally. With increasing age BUT decreased, the threshold to CO2 increased, and irritation intensity to CO2 decreased. A gender difference was observed -ED was increased in women. There was no relationship between the outcomes of these three methods. Reduced BUT was seen among subjects rating high levels of exposure to dust, electrostatic fields, and dry air, while ED increased with high temperatures.
Eye blinking is essential for maintenance of the eye tear film. Therefore, measure of eye blink rate may be used to study pre-corneal tear film integrity influenced by eye blinking efficiency 37. Sjogaard et al. (2005) 38 used the electro-oculogram (EOG) as a measure of eye blink rate during computer work. The EOG was evaluated against video recordings as an easy-to-use measure of eye blinking and was therefore considered a potential method for quantifying eye blinks during prolonged working periods.
Recent studies contributed to the topic of effects of indoor and outdoor air pollution on the human eye surface. Leonardi A. and Lanier B. (2008) 39 described the so called "urban eye allergy syndrome". These authors showed that in a significant number of patients who presented in outpatients clinics with conjunctivitis, it could not be categorized either as an allergic, or infectious, or "dry eye" conjuntivitis. Patients who are affected by this pseudo-allergic form of vasomotor or idiopathic conjunctivitis usually live in urban polluted areas and may be affected by a new clinical entity. Both, allergens and pollutants, can directly initiate specific and nonspecific mucosal inflammation through several interweaving mechanisms. Novaes P. et al (2007) 40 detected a positive and significant association between exposure to air pollution and goblet-cell hyperplasia in human conjunctiva using the combination of simple measurements of exposure to air pollution and impression cytology which was found to be an effective and noninvasive approach for characterizing human response to ambient levels of air pollution. Bakke JV and co-workers (2008) 41 presented the association between airway symptoms, complaints on environmental perceptions, atopy definitions and biomarkers including tear film stability (BUT), nasal patency and nasal lavage (NAL). Personal predictors (gender, age, smoking, infections) for these biomarkers, as well as, associations between the biomarkers were also assessed. BUT was measured by a non-invasive method (NIBUT) and self-reported impression (SBUT). In NAL following parameters were analysed: eosinophilic cationic protein (ECP), myeloperoxidase (MPO), lysozyme and albumin. Total serum IgE, and specific IgE using Phadiatop was measured. Data on subjective symptoms, environmental perceptions and background data were collected by use of a questionnaire. Authors concluded that BUT and NAL-lysozyme was associated with ocular, nasal, laryngeal symptoms and indoor environmental perceptions. Ever having had asthma and ever having had hay fever were predictors for symptoms and perceived air quality, respectively. Phadiatop, Total IgE, familiar allergy and ever eczema were not associated to symptoms or perceived environments. Age, gender and Phadiatop were main predictors for ocular and nasal biomarkers.
Color vision is known to deteriorate as a consequence of neurotoxic agents (solvents) at work. This deterioration is correlated with the duration and exposure intensity. Research on this topic was comprehensively covered by Iregren et al. (2002) 42 in their review of literature published until December 2000 on color vision and occupational chemical exposures. Briefly, several types of tests of color vision are available including pseudo-isochromatic plates (The Standard Pseudoisochromatic Plates, The Ishihara plates, The American Optical plates, The City University tritan), Color Arrangement Tests (The Farnsworth D15, The Farnsworth-Munsell 100-hue test (FM 100), and The Lanthony D15 de-saturated panel), and some others. Industrial exposures to styrene, toluene, perchloroethylene, carbon disulphide, and n-Hexane were studied mainly using the Lanthony D15 and FM 100 tests. It was found that long-term exposure to even low levels of styrene and to carbon disulphide (strongly associated with exposure levels) may negatively affect color vision. It was found that long-term low-level exposure to carbon disulfide causes acquired color vision deficiency 43. The deterioration of color vision caused by n-Hexane and perchloroethylene could be detected even in small increase of the exposure level. In addition, Iregren et al. (2005) 44 performed another study on acute occupational styrene exposure and color vision in 108 workers (21-65 years) at Swedish reinforcement plastic plants. Color vision was tested in this study by the Lanthony D15 desaturated panel binocularly test without prior training (ample light 1400 1x). That study indicated that acute styrene exposure even at levels below the current Swedish OEL of 20 mg/m3 negatively affects color vision.
The age-related cataract is another very important eye condition which is probably also influenced by different out - and indoor air pollution. According to World Health Organization (WHO) more than one million people become blind and cataract accounts for more than 50% of those cases. The prevalence of cataract is higher in developing countries and affects more females than males 45-48. The risk factors for cataract formation are not yet fully understood. A broad scale of factors may influence cataract formation. Among them are age-related factors, active cigarette smoking, exposure to UV- radiation (sunlight), radiation, microwaves, high temperatures and metabolic conditions such as malnutrition, diabetes, and chronic severe diarrhea. Exposure to indoor air pollution from the combustion of traditional biomass fuels (wood, charcoal, animal dung, and crop wastes) and coal is a significant environmental hazard, predominantly affecting the population in developing countries 49-51. There is consistent evidence that exposure to biomass smoke increases the risk of a range of common diseases of both children and adults 46, 51. Recently, several epidemiological studies have provided evidence of an association between cooking with solid fuels and cataract formation or blindness 52-54. Wood combustion was found to be an important factor in the etiology of age related cataract. Typical occupational cataracts were thoroughly described in ore-melting oven (steel) workers; workers exposed to organic solvents (TNT) and ionizing radiation (rarely seen nowadays do to efficient technical protection).
Retina and retinal vessels
Although it was estimated that fine particulate air pollution and ozone are associated with increased cardiovascular events and that short-term inhalation of fine particulate air pollution and ozone at concentrations that occur in the urban environment cause acute conduit artery vasoconstriction, there is hardly any evidence of the effect of air pollution on the retinal and choroidal vessels.
Remky et al. (2004) 55 determined retinal vessel diameters by non-mydriatic fundus photography in an ergo-medical field study with the occupational exposure to carbon disulfide (CS2). These authors found that chronic exposure to carbon disulfide may lead to retinal vascular changes and retinopathy. In a field study blinded to the history of occupational CS2 exposure, 505 employees of two rayon production plants were investigated. Retinal vessel diameter measurements (one eye per subject) were performed in digitized images in the temporal vessels in one disk diameter distance to the optic disk using the half height method in grayscale profiles (Matrox inspector - R). While venous diameters were significantly larger in 166 subjects exposed to CS2 than in 140 non-exposed subjects, there was no significant effect of CS2 exposure on arterial diameters. But, both, the arterial and the venous diameters were negatively correlated with age. Furthermore, the arterial diameters were correlated to arterial blood pressure. Remky and coworkers concluded that occupational CS2 exposure in a larger cohort, lead to significant changes of retinal venous diameters. Authors suggested that non-mydriatic fundus photography including diameter measurements is a useful tool in toxicological studies. Recently, Resch and coworkers (2005) 56 investigated the effect of inhaled CO on retinal and choroidal blood flow. It has been hypothesized that carbon monoxide (CO) acts as an important vascular paracrine factor and plays a role in blood flow regulation in several tissues. Fifteen healthy male volunteers were studied in a randomized, double-masked, placebo-controlled design. CO in a dose of 500 ppm or placebo (synthetic air without CO) was inhaled for 60 minutes. Ocular hemodynamics was measured at baseline and at 30 and 60 minutes of inhalation. Retinal blood cells (RBC) velocity was assessed using bidirectional laser Doppler velocimetry. Fundus pulsation amplitude (FPA) was measured using laser interferometry, and submacular choroidal blood flow using laser Doppler flowmetry. These authors found that CO breathing caused the widening of retinal arteries and veins indipedent of the significant increase of carboxyhemoglobine. Calculated parameters, such as retinal blood flow, subfoveal choroidal blood flow, and FPA, increased significantly in response to CO inhalation. It remains unclear whether this increase is caused by tissue hypoxia or another mechanism. On the other hand, no changes in the retinal microcirculation were revealed during serial fundoscopy studies, which investigated the effects of sustained low-level elevations of carbon dioxide on cerebral blood flow and autoregulation of the intracerebral arteries in humans 57. Cerebral blood flow velocity (CBFv) was measured by insonating the middle cerebral arteries of four subjects using a 2 Mhz transcranial Doppler. CBFv was found to be elevated significantly during the first 1-3 days post exposure, after which CBFv progressively readjusted to pre-exposure levels. Slivka and collaborators hypothesized, that time-dependent changes in CO2 vascular reactivity might be caused either by retention of bicarbonates in brain extracellular fluid or by progressive increases in ventilation, or both.
Recent studies have suggested that exposure to exhaust particles and ambient air pollution increases carotid intima-media thickness and reduces ocular blood flow velocity. Memisogullari R. et al (2007) 58 assessed the relationship between serum homocysteine, a potential parameter for atherosclerosis, and the ocular blood flow velocity and the resistivity index in highway toll collectors. The peak systolic and end diastolic flow velocities and the resistivity index were measured in 22 toll collectors and 24 control subjects by color Doppler ultrasonography. Authors showed significant correlations between the serum homocysteine level and ophthalmic artery resistivity index in both highway toll collectors (p < 0.001) and controls (p < 0.005). Authors suggested that the exposure to exhaust particles might increase the serum homocysteine level, which in turn could lead to the decreased ocular blood flow and the increased resistivity index.
The environmental tobacco smoke (ETS) has been proposed to be a risk factor, including age-related macular degeneration, Graves ophthalmology, glaucoma, uveitis, refractive errors, strabismus, tobacco-alcohol amblyopia, non-arteritic ischaemic optic neuropathy, Leber optic neuropathy and diabetic retinopathy 59. To better understand the cellular and molecular basis for the epidemiologic association between cigarette smoke and age-related macular degeneration (AMD), Sharma A. and co-workers (2008) 60 examined the effects of Benzo(e)Pyrene (B(e)P), a toxic element in cigarette smoke, on human retinal pigment epithelial cells (ARPE-19). These results show that B(e)P is a toxicant to human retinal pigment epithelial cells in vitro. It causes cell death and induces apoptosis by the involvement of multiple caspase pathways. Klein R. et al (2008) 61suggested as well that smoking appears to be related to the long-term incidence and progression of AMD.
Many conditions, in which free radicals are generated e.g. sunlight, cigarette smoke, air pollution, infection, and metabolic processes can cause damage to the layers of retinal vessels and induce neovascularization. Both, diabetic retinopathy and wet age-related macular degeneration (AMD) are together responsible for the majority of progressive blindness in the world today. In both of these diseases the induction of new aggressive blood vessel growth consecutively leading to edema, macular thickening, bleeding in the eye, and eventual scarring of the retinal tissues can result in the rapid loss of vision.
Light damage and retina
The influence of light exposure on retinal damage is an important subject of clinical and experimental studies. We can only briefly focus on this issue in the present overview. It is well established that ultraviolet (UV) and visible radiation has the potential to damage the retina and pigment epithelium 62. The human retina is only exposed to the "visible component" of the electromagnetic spectrum from 400-760nm and some short-wavelength infra red (IR). This part of the electromagnetic spectrum may result in chronic or acute tissue damage when it is absorbed by any one of a number of photosensitisers or chromophores e.g. the visual pigments, melanin, melanopsin, lipofuscin, flavins and flavoproteins. Evidence collected since the 1970s suggests that light may damage the retina in a number of ways involving different chromopores and cellular events 63. Short-intense exposure (100ms-10s) may result in thermal damage when incident energy is absorbed by a tissue and there is a significant rise in local temperature. The action spectra for this type of damage is dependent on the absorption characteristics of the chromopore but typically peaks in the blue/green, green and red regions of the visible spectrum 64. Although such exposures are used therapeutically, to produce retinal photocoagulation, they are not encountered in the natural world.
Longer exposure (typically quoted as being 10s and longer) to much less-intense light sources may cause retinal damage by a photochemical mechanism. It seems to be the same mechanism that is most likely to be of relevance to the development of AMD.
Photochemical reactions take place in normal ambient conditions and involve a reaction between energetic photons and an absorbing molecule. In the presence of oxygen this reaction leads, via a number of intermediary steps, to the production of reactive oxygen species (ROS) including singlet oxygen, superoxide, hydrogen peroxide and hydroxyl radicals. These ROS are highly toxic and can cause lipid peroxidation, protein oxidation and mutagenesis. Althought ROS production is a natural by-product of cellular respiration it is believed to have a major role in ageing 65 and contributes to the development of AMD. In the comprehensive review Margrain et al. (2004) 66 evaluated the long-held belief that blue light exposure has a role in the pathogenesis of AMD. The precise chromopore that may be involved in the pathogenesis of AMD is unclear but the age pigment lipofuscin is a likely candidate. Its aerobic photoreactivity and adverse effects on antioxidant activity combined with its gradual accumulation over time suggests that its in vivo phototoxicity increases with age despite changes in the absorption characteristics of the crystalline lens. Evidence from animal studies confirms blue light's damaging potential but the results are not directly applicable to macular degeneration in humans. Studies of human macular pigment density and the risk of AMD progression following cataract surgery lend further weight to the hypothesis that blue light exposure has a role in the pathogenesis of AMD. The role in retinal photodamage of flavins and porphyrins, present as prosthetic groups of several important enzymes, is still poorly understood. Lipofuscin, which accumulates during ageing in the retinal pigment epithelium (RPE), is a potent photosensitiser, which photogenerates singlet oxygen, superoxide anion, hydrogen and lipid peroxide. However, it is still unknown which molecular constituent of lipofuscin is responsible for its photoreactivity. Melanin has been rejected as a potential candidate responsible for photochemical damage to the retina based on observations of the similarity of end-points in photodamage in albino and pigmented animals; however, the same observations may raise the possibility that in pigmented animals photoprotective effects must balance the photodamaging effects of melanin in pigmented animals, as melanin absorbs a significant fraction of incident photons. Macular pigment is most likely to play a protective role as a blue light filter and possibly as an antioxidant, but more experimental evidence is needed to support this hypothesis 64. Authors suggested that a better understanding of the photo-induced processes in the retina may help to predict what levels of illumination are safe for the normal retina and to specify the conditions under which even ambient solar radiation may impose a risk of retinal photodamage.
In conclusion, this paper presents an overview of known ophthalmologic consequences of pollution, environmental and occupational factors. A survey of the literature shows that very little information is available regarding the effects of occupational or environmental pollutants on the eye, in particular on retina and retinal vessels. It was noticed that most of the studies dealt with the conditions of the ocular surface, and used eye irritation as the criterion for the effects of air pollutants. Conditions such as discomfort eye syndrome and dry eye syndrome are the most common complaints in different occupations, predominantly in computer workplaces with high mental concentration to the subject dealt with. Eye irritation depends on destabilization and break-up of the outer-eye tear film and may explain eye conditions among the population in terms of occupational, climate, and eye-related physiological risk factors. The increased frequency and severity of lens opacities has been shown to be related to exposure to combustion of different fuels, in particular biofuels. Color vision has been found to be very sensitive to chronic exposure to many industrial chemicals, mostly organic solvents. Retinal vascular changes and retinopathy after chronic exposure to carbon disulfide and changed retinal and choroidal hemodynamics after exposure to carbon monoxide were investigated as models for occupational effects of these gases. It was found that CS2 caused the increase in retinal venous diameters and CO caused the increase in arterial and venous diameters, retinal blood flow velocity, and fundus pulsation amplitude. The influence of light exposure on retina damage, potential confounding factors and the photochemical mechanism were discussed.
Occupational hygiene measures, such as decreasing the level of particles and gaseous air pollutatnts at the workplace as well as optimizing illumination and humidity at the workplace are the major steps in prevention of eye disease. Occupational medicine biomonitoring (prior to the development of an eye-disease) in terms of yearly eye check-up, including visual acuity, Schirmer Test, BUT, and ophthalmoscopy at occupationally disadvantaged microclimatic conditions or high eye strain should be the second level of intervention in preventing chronic eye damage.
Prospective longitudinal research in environmental and occupational medicine is needed in order to improve the understanding and diagnostic approach to ocular damage caused by environmental and occupational factors. These studies will help to understand the long term environmental and occupational effects on the eye, which superimposes on the aging processes in the constantly aging working population as the consequence of the actually evolving demographic shift. The insights in the mechanisms of these events may help us develop preventive measures during working life, not only in preventing occupational diseases, but using occupational surveillance to counteract ocular disability of the advanced age.
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