Anthony P. Cullen

Health effects from stratospheric ozone depletion and interactions with climate change

The potential health effects of elevated levels of ambient UV-B radiation are diverse, and it is difficult to quantify the risks, especially as they are likely to be considerably modified by human behaviour. Nevertheless epidemiological and experimental studies have confirmed that UV radiation is a definite risk factor for certain types of cataract, with peak efficacy in the UV-B waveband. The causal link between squamous cell carcinoma and cumulative solar UV exposure has been well established. New findings regarding the genetic basis of skin cancer, including studies on genetically modified mice, have confirmed the epidemiological evidence that UV radiation contributes to the formation of basal cell carcinomas and cutaneous melanomas, For the latter, animal models have demonstrated that UV exposure at a very young age is more detrimental than exposure in adulthood. Although suppression of certain immune responses has been recognised following UV exposure, the impact of this suppression on the control of infectious and autoimmune diseases is largely unknown. However, studies on several microbial infections have indicated significant consequences in terms of symptoms or reactivation of disease. The possibility that the immune response to vaccination could be depressed by UV-B exposure is of considerable concern. Newly emerging possibilities regarding interactions between ozone depletion and global climate change further complicate the risk assessments for human health but might result in an increased incidence of cataracts and skin cancer, plus alterations in the patterns of certain categories of infectious and other diseases.

Photokeratitis and Other Phototoxic Effects on the Cornea and Conjunctiva

Except when sleeping, the cornea and interpalpebral conjunctiva are exposed to the ambient environment, both natural and man-made. Levels of solar ultraviolet irradiance reaching the eye may exceed the damage threshold under a number of circumstances. The consequences of overexposure may be acute after a latent period, sequelae to an acute exposure, or long-term chronic effects. Previously derived action spectra for photokeratitis and photoconjunctivitis due to incoherent ultraviolet are presented. These reveal interspecies similarities for the levels of radiant energy reaching each tissue. The initial in vivo (clinical) signs of photokeratitis are due to lost or damaged epithelial cells with other signs produced by this primary response. The conjunctival signs include injection and chemosis. Chronic exposure to solar ultraviolet is a factor in climatic droplet keratopathy and pterygium. Phototoxic compounds or their by-products potentially can reach the cornea from the air, via the tears or aqueous humor, or from the limbal capillaries. However, the human cornea appears to be much less susceptible to the influence of phototoxic agents than the skin.

Long-term effects of a single dose of ultraviolet-B on albino rabbit cornea--I. in vivo analyses.

Abstract Both eyes of female albino rabbits (1.9 kg) were exposed to a single dose of UV‐B (300 ± 9 nm; 0.125 J/cm2 total dose) between 13.30 and 15.00 h. The average irradiance was 209 ± 4 μW/cm2 delivered over 612 ± 13 s. At various time periods thereafter (every 12 h for 3 days, 6, 7, 14, 28, 42, 56, 112, 224 and 336 days post‐irradiation), the animals were subjected to a full slit lamp examination to evaluate the status of the cornea and the anterior segment along with optical or ultrasonic pachometry of central corneal thickness. The results were compared with studies on age‐matched rabbits over the same time period. In response to the UV‐B irradiation, the corneas showed a modest edema (20% increase in central corneal thickness) that peaked at 48 h. Nearly normal central cornea] thickness returned in 6 days and followed by a secondary very slight swelling (< 5%) that resolved by 14 days. The edema was accompanied by keratitis over the same period. Thereafter, both control and UV‐B irradiated corneas progressively increased in thickness with age. Biomicroscopy also revealed the appearance of granular opacities in the corneal epithelium that peaked at 72–96 h and resolved over 28 days. In addition, very small microdot opacities of the corneal epithelium were present in the UV‐B irradiated corneas that reached maximum at 72 h but persisted to some degree throughout the evaluation period. Biomicroscopy also revealed a progressive disruption of the homogeneous nature of the corneal stroma by the appearance of large ‘bread crumb’‐like opacities that started at 72 h and was still present at the end of the evaluation period. These results suggest that long‐term evaluation of the cornea is important after acute UV‐B exposure and indicate that acute exposure to UV‐R can produce corneal changes resembling those reported following chronic exposure to UV‐R‐rich environments.

Determination of infrared radiation levels for acute ocular cataractogenesis.

One hundred pigmented rabbit eyes and ten primate eyes were exposed to infrared (IR) radiation in the 715 to 1,400 nm wavelength range and to the full spectrum output from a 5,000 W Xenon high-pressure source. The ocular exposures were evaluated independently with a slitlamp by two researchers and classified for ocular damage. The primary ocular lesions resulting from exposure to IR radiation were corneal, iritic, and lenticular. Corneal damage varied from epithelial haze to epithelial erosion but no endothelial damage was found. The iris showed stromal haze and swelling. Lenticular changes showed small white dots that, occur at the level of the anterior cortex. All lens damage depended on iris involvement. Ocular damage was related to the rate of delivery of the IR radiation since the data show that as the irradiance level increases, the radiant exposure threshold decreases. Exposures for the full spectrum were found to be additive for irradiance levels at 4 W-cm−2 and above. The threshold radiant exposures for the full spectrum of 750 J · cm−2 for the cornea, 1,000 J · cm−2 for the iris, and 2,000 J · cm−2 for the lens were essentially identical to the IR exposure thresholds for the same irradiance levels. The primate threshold radiant exposure was a factor of six above the respective rabbit thresholds.

Ultraviolet induced lysosome activity in corneal epithelium

A 5,000 W Xe-Hg high pressure lamp and a double monochromator were used to produce a 3.3 nm half-bandpass ultraviolet radiation at 295 nm. Pigmented rabbit eyes were irradiated with radiant exposures from 140 Jm−2 to 10,000 Jm−2 and evaluated by slit-lamp biomicroscopy, light and electron microscopy. Corneal threshold (Hc) was 200 Jm−2 and lens threshold (HL) was 7,500 Jm−2. The most repeatable and reliable corneal response to these levels of UV was the development of corneal epithelial granules. Histological changes included a loss of superficial epithelial cells and selective UV induced autolysis of the wing cells. It is suggested that the biomicroscopically observed granules are the clinical manifestation of the secondary lysosomes revealed by light and electron microscopy. It is proposed that UV breaks down the primary lysosome membranes to release hydrolytic enzymes which in turn form the secondary lysosomes during autolysis. Extreme levels of radiant exposure at 295 nm result in indiscriminate destruction of all layers of the corneal epithelium, but the posterior cornea was spared. Mit Hilfe einer 5 000 W Xenon-Hochdrucklampe und einem Monochromator wurde eine UV-Bestrahlung bei 295 nm Wellenlänge mit einer Bandbreite von 6,6 nm durchgeführt. Dabei wurden die Augen pigmentierter Kaninchen Bestrahlungswerten zwischen 140 Jm−2 und 10000 Jm−2 ausgesetzt und spaltlampenmikroskopisch sowie licht- und elektronenmikroskopisch untersucht. Der Hornhaut-Schwellenwert (Hc) lag bei 200 Jm−2 und der Linsenschwellenwert (HL) bei 7500 Jm−2. Die konstantesten Veränderungen in der Hornhaut bei UV-Bestrahlungen in diesem Schwellenwertbereich waren das Auftreten von Granula im Hornhautepithel. Weitere histologische Veränderungen bestanden in einem Verlust der oberflächlichen Hornhautepithelzellen und selektiver UV-induzierter Autolyse der sogenannten Flügelzellen. Es wird vermutet, daß die biomikroskopisch sichtbaren Granula die klinische Manifestation der licht- und elektronenmikroskopisch darstellbaren sekundären Lysosomen darstellen. Es wird angenommen, daß die UV-Bestrahlung zu einem Zusammenbruch der Membran primärer Lysosomen und damit zur Freisetzung hydrolytischer Enzyme führt, was die Bildung sekundärer Lysosomen während der Autolyse zur Folge hat. Extreme Bestrahlungsdosen bei 295 nm führen zu einer nicht mehr abgrenzbaren Zerstörung aller Sichten des Hornhautepithels; Veränderungen an der Hornhautrückseite finden sich dabei allerdings nicht.

Acute effects of ultraviolet-B irradiation on the corneal surface of the pigmented rabbit studied by quantitative scanning electron microscopy

Abstract. The eyes of female pigmented rabbits were exposed to a single dose of UV‐B (300 + 9 nm, 0.05 J/cm2 total dose) between 13.30 and 15.00 h. The average irradiance was 225 + 36 μW/cm2 delivered over 191 to 264 s. At various time periods thereafter (24, 48, 72 and 96 h post‐irradiation), the animals were euthanized by pentobarbital overdose and the eyes fixed with 2% glutaraldehyde in 80 mM cacodylate buffer (pH 7.4, total osmolarity of 330–340 mOsm/L). Corneal quadrants were examined by high resolution scanning electron microscopy at 100 × and 500 × at‐stage magnification at central, mid‐peripheral and peripheral sites. The micographs from the central cornea were subjected to a quantitative analysis using a computer based digitization system. A peak effect was observed at 48 h at which cellular exfoliation was noted at the corneal apex. In the region immediately adjacent to the exfoliating cells, the number of light and dark electron reflex cells decreased to 48 h while the numbers of medium‐reflex cells decreased after 48 h. The relative surface area of all cells was also decreased at 48 h compared to unirradiated controls. Significant recovery was observed by 96 h. Mid‐peripheral and peripheral sites were largely unaffected by this just supra‐threshold irradiation.

Corneal swelling and recovery following wear of thick hydrogel contact lenses in insulin-dependent diabetics

Thick, 0.34 mm, 38% water hydrogel lenses were fitted, under a pressure patch, to one eye of 18 type I diabetic patients (aged 18-40 years) to assess the acute response to hypoxia and hypercapnia; the response was compared with that in 18 healthy, aged-matched non-diabetic subjects; the closed-eye lens wear was started mid-morning. Pre-lens wear assessments were made of acuity, intraocular pressure (IOP), central corneal thickness (CCT) and corneal appearance by biomicroscopy. The mean duration of the diabetes was 13 +/- 7 years and the average fasting blood glucose was 8.7 +/- 3.3 mMl-1. Baseline CCT values were marginally greater in diabetic patients (600 +/- 33 microns) compared with a group of non-diabetic control subjects (584 +/- 26 microns; P > 0.5). A 7.7 +/- 2.1% increase in CCT was measured after 3 h lens wear in the diabetic patients while an average 10.6 +/- 2.4% increase in CCT was measured in the control subjects (P < 0.05). The recovery of corneal thickness to baseline values in diabetic patients was slower (at 44.8 +/- 2.0% per hour) than the control subjects (53.9 +/- 2.1 per hour; P < 0.05) although recovery of corneal thickness occurred in both groups within 2.5-3h. IOP values (non-contact tonometry) were higher in the diabetic patients than in the controls (14.5 +/- 2.9 vs 12.4 +/- 1.7 mmHg; P < 0.01). Overall, those corneas with greater baseline CCT values tended to swell less than those with lower baseline CCT values (r = 0.582). Positive correlations were also found between corneal thickness and IOP and blood glucose. The diabetic patients thus tended to have slightly thicker corneas (but this could be related to blood glucose or IOP rather than true corneal disease) and also had corneas that tended to swell less with a contact lens stress test (but this could be constitutively due to the slight oedema already present). The different corneal response in diabetic patients may thus be the result of physical determinants such as initial oedema and IOP and not the result of a disease of the cornea itself.

Physical characteristics and perceptual effects of blue-blocking lenses

The transmission-optical properties of a “blue-blocking” lens and its influence on several aspects of human visual performance were assessed. Results showed that the lens was effective in absorbing ultraviolet and blue wavelengths and that its effects on contrast sensitivity and visual evoked potentials (VEPs) were similar to those produced by an equivalent neutral density (ND) filter. Although the lens did not alter stereopsis, it did produce severe color discrimination losses for normal and dichromatic subjects.

Additive effects of ultraviolet radiation

Abstract A 5000 W xenon‐mercury high pressure lamp and a double monochromator were used to produce a 3.3‐nm half‐bandpass ultraviolet (UV) radiation at 295 nm. Pigmented rabbit eyes were irradiated with radiant exposures given in joules per cm2 and ranging from 0.014 to 1.0 J•cm‐2 and evaluated by slitlamp biomicroscopy. Corneal threshold (Hc) was 0.05 J•cm‐2 and lens threshold (HL) was 0.75 J•cm‐2. Other eyes were irradiated with 2 Hc and evaluated from 4 to 24 hr at 4‐hr intervals. After a latent period of 4 hr, the corneal response was observed to increase to a maximum by 12 hr. Additional eyes were subjected to repeated Hc and 0.5 Hc followed by Hc exposures with varying intervals between exposures. Corneal damage was only greater than that expected from a single Hc exposure if the separation between the two Hc exposures did not exceed 8 hr. The subthreshold exposures did not sensitize the cornea to later Hc irradiations. The most repeatable and reliable corneal response to these levels of UV was the development of corneal epithelial granules.

The cornea swells in the posterior direction under hydrogel contact lenses

Two mathematical models were developed to describe the topographical corneal swelling response to hydrogel contact lenses and the effect of these changes on refractive error. In one, corneal thickness changes resulted in deformation of the anterior corneal surface. In the other, the posterior surface only was deformed. Refractive error, corneal thickness and corneal shape were monitored in a sample of adapted contact lens wearers with one eye patched for 4  h while wearing a soft contact lens. The experimental data were most consistent with the model in which the posterior surface only was deformed.