Ординатура / Офтальмология / Английские материалы / Progress in Lens and Cataract Research_Hockwin_2002

Historical Evidence

A number of in vitro laboratory studies have shown that UVR can produce optical changes in lens proteins that could explain at least one causal factor in some forms of cataractogenesis [26–30]. Cataracts have also been produced in rabbits and rodents from acute exposure to UVR in the 295–320 nm UV spectral band [22–25]. Additionally, several epidemiological and related studies have suggested a relationship between outdoor ambient UVR levels and the incidence of corneal degeneration and some types of cataract [1, 2, 5, 8, 9, 11, 17, 36]. Weale [37] estimated that a factor of ten in the incidence rate of cataract was due to light. However, Miranda [15, 38] argued that the incidence of cataract in tropical and semitropical climates actually showed a stronger correlation with ambient temperature than with sunlight. Miranda [15] noted that Punjabi (India) villagers in high altitude mountain environments had a lower incidence of cataract than villagers at the same latitude living in the plains below [16]. Harding [39] made similar arguments regarding the lower incidence of cataract at high elevations. However, such arguments ignore the geometrical exposure factors. Although the solar UVR exposure from overhead increases and average air temperature decreases with higher elevation, this apparent contradiction to the UVR hypothesis is misleading, since (as noted by Brilliant et al. [14]) the shading effect of mountains in most Nepalese mountain villages actually decreases the UVR exposure [33–35]. Sliney measured this reduced ocular exposure from UVR in different environments. Mountains produce extensive shady areas; this shade is minimal during the midday periods when UVR ground irradiances are the highest. The diffuse UVR coming from the near-horizon sky also decreases at high elevations. Thus, a more refined inspection of these physical factors appears to be warranted.

The in vivo temperature of the crystalline lens is difficult to measure but varies with direct radiant heat load and corneal temperature. Corneal temperature varies from approximately 28 °C in a freezing gale to 33–37 °C in the tropics [40–45]. The lens temperature will be shown to vary from approximately 33 °C, or even less, in very cold winter climates, to about 37 °C in inland tropical environments and hot industrial workplaces. A life-long elevation of lens temperature could well have an adverse impact upon the lens. Indeed, Miranda [38] and Weale [37] both argued that the age of onset of presbyopia is earlier in warm climates and this age varies inversely with the average ambient temperature. However, Taylor [46] reported that no correlation appeared to exist with variation of ambient temperature in an epidemiological study in Australia. With this historical background, we decided to examine the ocular exposure to heat and UVR more quantitatively.

Materials and Methods

The relationship of environmental measures of temperature and solar UVR was studied as they relate to the actual UVR exposure dose to the cornea and lens and to the internal temperatures of the eye, respectively. The thermal dosimetry will be presented first.

Calculations and Measurements of Ocular Temperatures

Several investigators have reported measurements of corneal, retinal and other intraocular temperatures in the rabbit eye [47, 48]. Unfortunately, accurate measurements of internal temperatures of the eye are extremely difficult, since measurement probes can perturb the local temperature and introduce significant errors. The use of anesthesia will also influence the results. Furthermore, the human thermoregulatory system is superior to that of the rabbit so that extreme caution is necessary in extrapolating these experimental animal measurements to the awake or sleeping human. Although the reported temperatures for the rabbit lens varied from 29 to 38.7 °C (with retinal temperature of 40 °C) for an air temperature range from 0 to 28 °C in one early study [47], the corresponding estimated lenticular temperature variations in man are considerably less. Studies, employing air movement showed that corneal and lens temperatures would be less than for stagnant air; e.g., the temperature of the lens dropped from 36 °C (stagnant air) to 34 °C for air at 23 °C moving at 5 m/s. Lagendijk [45] developed a mathematical model to calculate temperature distributions in the human eye during hyperthermic therapy where radiant losses can be ignored. The results from this model were employed as an aid in estimating internal lens temperatures [4].

Ambient Temperature and Corneal Temperature

Of interest in this study are the ambient temperature variations in the human lens for variation in air temperature. The corneal temperature is strongly affected by the external environment, whereas the retinal and choroidal circulation stabilizes the temperature at the retina to approximately 37 °C. The temperature in the lens is approximately 35.5 °C and in the cornea 34.8 °C at a room temperature of 22 °C. With the external temperature raised to hyperthermic conditions and the corneal temperature elevated to 43 °C, the retina remains at 37 °C, but the lens temperature elevates to 41 °C. With an ambient temperature of 10 °C, the corneal temperature drops to 31 °C [48], and the calculated lenticular temperature falls to about 33 °C. Therefore, assume that in temperate climates, the lens temperature is typically about 35.5–36 °C, whereas, in the tropics, the lens temperature is probably about 36 °C and may be as high as 37 °C. Thus, the difference in the average temperature of the lens between two individuals, a native of the tropics and a native of North America, is not very great. Nevertheless, a lifelong temperature elevation of 1–2 °C may still be sufficient to have an impact upon thermal coagulation of proteins. It must be remembered that thermal damage to tissue does not have a single critical temperature threshold, but thermal denaturation of proteins occurs at all times; the normal cellular repair processes are adequate to contend with limited damage at the cellular level [4]. Figure 1 summarizes the temperature gradients for different environments.

Industrial and Other High-Heat Environments

The conventional view has been that industrial ‘heat cataract’ results from chronic exposure of the iris and lens to near-infrared radiation that elevates the lenticular temperature [4, 32]. If high ambient temperature separately influences cataractogenesis, it is worthwhile

UVR Exposure Dose

Over the past 3 decades, to determine ocular exposure dose to UVR, my laboratory has conducted an extensive series of UVR measurements of sky conditions, ground surfaces, or mannequin exposure. The details are too complex to present here [33–36, 50]. Only the key findings and broad observations can be provided. All of these studies showed that serious errors resulted if one attempted to estimate UVR ocular exposure by relying on subjective experience of the meteorological environment similar to what we can see in the visible spectrum. From our studies, it is possible to picture the ambient UVR environment when standing outdoors.

By contrast with visible light, UVR is very strongly scattered by atmospheric molecules, and this scatter increases greatly with decreasing wavelength toward the blue and ultraviolet spectral regions. For this reason the sky is blue. If one could see only in the UV-B spectrum (280–315 nm), a clear sunny sky would appear very hazy; the sun would be barely visible through the haze; ground shadows would be very fuzzy; green grass with a reflectance of 1% would appear pitch black, and sand and most ground surfaces would appear very dark gray, like an asphalt roadway. The most actinic UVR (UV-B) exposure arriving at the face would be from diffuse scatter and not from direct sunlight. Standing over water, one would see a reflection of the gray sky. Cumulus clouds would appear darker or lighter than the brilliant ‘blue’ portion of the sky, depending upon whether the cloud reflected or blocked direct sunlight exposure.

In addition to our studies of the geometrical distribution of UVR in skylight and from ground reflection, we also conducted several studies of the anatomical, physiological and behavioral factors that could influence ocular exposure to UVR, light and infrared radiation in the outdoor environment. Taken collectively, we concluded that geometrical factors dominate the determination of UVR exposure of the eye and the concentration of light across the retina. The degree of lid opening limits ocular exposure to rays entering at angles near the horizon. Clouds redistribute overhead UVR to the horizon sky. Mountains, trees and building shield the eye from direct sky exposure. Most ground surfaces reflect little UVR. One counterintuitive result is that the highest ocular UVR exposure occurs during light overcast where the horizon is visible and ground surface reflection is high. By contrast, exposure in a high mountain valley with green foliage results in a much lower ocular dose, even though the ambient meteorological UVR measure can be very high at such high elevations. Even if one stands on a mountaintop, the horizon UVB radiance can be less than if one is at sea level, where the global UVR may be lower! Other findings of these studies show that retinal exposure to light and UVR in daylight occurs largely in the macula and superior retina. An action spectrum for any UVR bioeffect is

Fig. 2. Penetration of different UV wavelengths. Although most of the shorter wavelength, more biologically active UV-B, is absorbed by the cornea, it is this spectral region that is known to produce experimental cataracts most readily in animals.

necessary to quantify the ocular exposure. Since an action spectrum exists only for acute-exposure cataract (295–320 nm), biologically relevant measurements in this spectral region are difficult. Principles of photochemistry predict that effects should be strongly wavelength-dependent and that the shortest wavelengths are generally more hazardous to biological molecules. At wavelengths less than 290 nm all incident UVR is absorbed in the cornea, and as the wavelength increases to 300 nm trace amounts of UVR reach the lens, and by 315 nm, the cornea transmits nearly half the incident radiation. UVR is absorbed largely in the lens at wavelengths greater than approximately 340 nm (fig. 2). Although most of the shorter wavelength, more biologically active UVR (known as UV-B from 280–315 nm) is absorbed by the cornea (fig. 2), it is this spectral region that is known to produce cataracts most readily in experimental animals and was shown to be important in at least one epidemiological study [2, 5, 17]. Because of the strong scatter and diffusion of UV-B much of the UVR incident on the eye comes from skylight near the horizon. Hence, the lid opening is critically important in determining UV-B exposure of the lens [51].

Early studies by Sliney [50] suggested that a greater portion of UVR reaches the eye from scatter from clouds and reflections from ground surfaces than from direct sunlight. Therefore, directional UVR measurements of limited fields of view (FOV) were determined to be more relevant in determining the exposure to the eye than the global measurements that are more commonly reported. It was recognized that it was critical to know what types of environmental conditions would cause a high ratio of UVR to outdoor luminance. With this information and the characterization of the dependence of the vertical

Table 1. Reflectance of ICNIRP/ACGIH: effective solar UV-B from terrain surfaces [4]

visual field upon luminance, a relationship between the environment and the total UVR exposure to the eye could be found. The ground reflectance in the UVR was determined in order to understand what UVR would strike the eye when the lids were open. Table 1 provides representative reflectance values.

Methods for the FOV Studies

In early studies we exposed mannequin heads fitted with UV-B detectors as the ‘eyes’, and placed hats and sunglasses on the mannequin head to measure protective qualities. However, we soon realized that the mannequin UV detectors were receiving radiant exposure H from too large an acceptance angle (FOV). By observing and photographing individuals in different sunlit environments, it became clear that the lid opening greatly limited the ocular UV exposure by restricting the FOV. Attempts to quantify lid opening by photography proved too difficult to analyze. The position and diameter of the pupil along with lid thickness could not be accurately measured. We therefore measured FOV subjectively in different environments. Since the upper lid position acts as a ‘shade’ and limits the vertical visual FOV, we designed a simple measurement procedure to measure only the upper limit of the FOV. This permitted us to calculate the upper acceptance angle of light entering the eye. The position of the upper lid varies with scene luminance over a wide range of outdoor scene luminance, but the lower lid was shown not to begin to rise except in the very brightest conditions; hence, only the upper lid position was measured in a series of studies [34, 51].

While facial features, such as the brow ridge and cheek, function as an ‘aperture’ to limit the amount of light and UVR reaching the cornea and lens, the lid opening was shown to be the critical factor, and the degree of eyelid opening

was shown to vary quite predictably with environmental conditions. The eyelids, which react to the visual brightness, or luminance, of a setting, are instrumental in attenuating the amount of light that enters the eye. A mathematical correlation between the luminance and the amount of lid closure was sought, but first the FOV had to be measured. The resulting algorithm could be used to determine the amount of UVR that reaches the eye in different conditions. It is important to recognize that lid opening affects the regional area of the retina being illuminated, but not the local concentration of light at the retina (the retinal irradiance) in the illuminated area for a fixed, unoccluded pupil. However, lid opening greatly affects the total UVR exposure dose to the lens.

Since the goal of several of our studies was to develop an algorithm for the amount of UVR exposure an average person receives while outside during a lifetime, attempts were made to model human behavior as accurately as possible. While walking outdoors, most people do not look straight ahead, but downward at an angle that averages approximately 15° below the horizontal [52]. To account for this estimate, 50 subjects in the study by Deaver et al. [51] were instructed to look at an object a distance away at 15° below the horizontal. With this line of sight fixed, the upper vertical acceptance angle was measured. In addition, a second FOV measurement was taken while the subjects looked horizontally. The majority of tests show that the acceptance angle for each subject as measured from the line of sight remained the same regardless of this viewing angle. However, it is interesting to note that often the acceptance angle increased as much as 10–15° when the line of sight was below the horizontal. This might have been expected since the luminance of the ground is usually lower than that of the sky, causing less squinting.

Tests were performed in a variety of different luminance conditions ranging from a white wall on a bright sunny afternoon to dense trees on a heavily overcast morning. This luminance range spanned three orders of magnitude, reaching as low as 170 cd/m2, and as high as 15,000 cd/m2. To assure that the luminance was the primary determinant in the amount of squinting, subjects were also tested wearing two different pairs of sunglasses. Both pair reduced the luminance roughly by a factor of four (3.8 and 4.3), although one had lenses with an orange tint that blocked more strongly in the blue part of the spectrum while the other was a neutral tone lens. This test was only given to a random subset of the original 50 subjects. Since the FOV for no sunglasses was also measured at this time, there was an opportunity to compare results with previous measurements to determine the precision of the experimental technique.

For the same luminance conditions, the upper FOV angle of a group of subjects typically spans a range of about 25°. Figure 3 shows the spread of FOV values for two different iris groupings, dark (brown and hazel) and light (blue and green). Note that although the subjects having darker irises had slightly more

Table 2. Measured ICNIRP/ACGIH effective UVB from the sky with a 40° cone FOV [4]

Discussion

Characterizing Ocular Exposure Dose

We approached the problem of calculating ocular exposure by deriving a formula that split up the two major components of radiant exposure H: the ground

reflection component Hground (table 1) and the sky radiance source component Hsky (table 2). Each of these components includes a physically determined radiance and

a geometrical factor, the solid angle of acceptance determined by lid opening.

Each component is determined by a radiance L and the pupil’s solid angle of acceptance (i.e., FOV) in units of steradians (sr) for that hemisphere in one’s total visual field. This approach may appear at first to be an overly complicated way to determine total exposure; however, since the UVR source is our total surrounding and not just a single very small source as the sun by itself, this procedure is essential to avoid substantial errors.

Radiance has units of watts per square centimeter per steradian. To better understand the concept of radiance, consider the following example: if you stand in a dark room with one window, the amount of light falling upon your face is quite high when standing at the window, but as you back away, the facial illumination drops greatly. Although the total light (or UVR for that matter) entering the eye and passing through the lens changes greatly, the luminance (brightness) of the outdoor scene does not change. In light measurement, it is convenient to calculate the light level falling on one’s face by multiplying the luminance or radiance (brightness of the source) by the solid angle of the source (the window) to obtain the illumination or irradiance. This method has the great advantage that one need merely determine the source radiance (e.g., the sky) and then determine the solid angle corresponding to a lid opening, or the FOV

determined by a head wrap or hat. This is a somewhat similar approach to that used by Rosenthal et al. [56], and termed the optical ambient exposure ratio (OAER). The important additional factors that we have added are the impact of the greatly reduced solid angle of acceptance created by squinting and importance of horizon-sky radiance, and whether the horizon sky can be observed. Neither of these added factors affect the outcome of the Chesapeake Bay Waterman’s Study, but we feel that an increased risk factor may result from considering this approach for future epidemiological studies. More importantly, the FOV measurements along with the ambient UVR radiance measurements near the horizon clearly show that lenticular UV exposure increases with haze and cloud cover, since the lids open with reduced sky luminance, and the haze and clouds redistribute the available UVR to increase horizon UVR radiance. For example, as shown in table 2, the horizon-sky UV radiance at sea level can double with haze even though the overhead (zenith) UV remains the same (as illustrated for Z 70°, fifth column), and yet the horizon-sky UV radiance was less than one sixth of that value when measured on a mountaintop at 2,750 m when the sun was higher in the sky! It appears that the greatest change that takes place as one moves to a higher altitude is the reduction in the fraction of UV-B that is diffuse (sky scatter) compared to the direct component of global UVB. This phenomenon has a direct impact upon the findings of epidemiological studies. For example, the study of Mohan et al. [57] has been cited to contradict the UVR hypothesis [39], since Mohan et al. reported that all types of cataract decreased with greater cloud cover and it was mistakenly assumed that the ocular UVR dose was lower with greater cloud cover, since the global UVR decreased with increased cloudcover. Their findings actually support – rather than contradict – the UVR hypothesis of cataractogenesis. This example aptly illustrates why epidemiological studies have so often led to apparently conflicting results!

Deriving Exposure Algorithms

To summarize, when one is outdoors in bright sunlight, the palpebral fissure constricts. The upper lid gradually lowers as ambient environmental brightness (luminance) increases like an automated awning. Under extremely bright conditions, the lower lid moves up to produce a squinting reaction (fig. 2). Sunglasses and brimmed hats reduce the apparent luminance, but this also reduces the squinting process, while providing a sense of greater comfort in the outdoor environment. As explained later, this sense of comfort may not always be an indication of the level of protection.

The impact of all of these findings taken collectively is quite clear. The direct exposure of UVR of the upper cornea and pupillary area is quite limited, and if trees or buildings block the horizon sky, direct skylight exposure of the cornea is rare. It is therefore not at all surprising that the incidence of pterygium