Cutaneous and ocular ramifications of ultraviolet radiation.

In this article,the uses of photobiologic techniques such as ultraviolet B radiation and PUVA are discussed, as is a general review of their potential acute and chronic side effects. The authors then focus, in more extensive detail, on the potential acute and chronic ocular toxicity associated with these modalities.

Photosensitizing drugs and their possible role in enhancing ocular toxicity. Parker Heath memorial lecture.

During the past decade there has been a considerable resurgence of interest in the photochemical effects of ultraviolet radiation capable of penetrating through the cornea (300-400 nm), on the intraocular tissues. The ocular lens and retina have received the most attention. The last few decades have also witnessed the development of a new therapeutic regimen, namely photosensitizing (phototherapy), in which the patients are given known photosensitizing agents and exposed to nonionizing radiation (ultraviolet, and on occasion, visible radiation). Such therapy has caused some ocular side effects, which in most cases could have been prevented. Drugs that are known photosensitizers and are capable of intraocular penetration through the blood-aqueous and blood-retina barrier are discussed with respect to their known or potential photosensitizing and/or phototoxic effects on intraocular tissues.

Lenticular psoralen photoproducts and cataracts of a PUVA-treated psoriatic patient.

Psoralen photoproducts were identified in association with cataracts in a psoriatic patient several years after oral methoxsalen plus ultraviolet A light (PUVA) therapy. Patients should be required to wear adequate optical protection not only during PUVA therapy but 24 hours following ingestion of methoxsalen.

Psoralens and ocular effects in man and animals: in vivo monitoring of human ocular and cutaneous manifestations.

Optical spectroscopy (fluorescence, phosphorescence, and electron spin resonance) has demonstrated the presence of 8-methoxypsoralen (8-MOP) and its potential for photobinding (to DNA and proteins) in human and animal ocular lenses. Similar photobinding in other ocular tissues, particularly the retina, has also been shown to occur in the young eye (lens has not yet developed as an effective UVA filter) and in aphakic and pseudophakic eyes. Skin biopsies were performed on a series of patients before, during, and following psoralen photochemotherapy (PUVA). High-resolution phosphorescence spectroscopy of PUVA patients enabled us to monitor the presence of 8-MOP in the skin and blood samples. These data indicated that significantly higher levels of 8-MOP accumulate within the psoriatic skin compared with uninvolved areas and demonstrated the feasibility of monitoring 8-MOP metabolism by this method. A second series of patients who had been on chronic PUVA therapy for many years were also evaluated by this technique and all patients' eyes were monitored by UV slit-lamp densitography with respect to determining lenticular photodamage in "unprotected eyes" compared with protected and untreated controls. The latter data have delineated at least 3 cases of presumptive PUVA cataracts. Phosphorescence assays on lens matter derived from individuals with a clinical diagnosis of PUVA cataracts demonstrated a photoproduct identical with the previously reported triplet noted in the lenses from experimental PUVA-treated animals.

Psoralen--long-wave ultraviolet therapy and human cataractogenesis.

Cataract formation associated with psoralen--long-wave ultraviolet (P-UVA) therapy has been documented in experimental animals. Presumptive P-UVA cataracts in humans have also been reported recently. Cataracts from two patients on P-UVA therapy were subjected to high-resolution phosphorescence spectroscopy. The lens homogenates from these two patients showed phosphorescence peaks identical (in shape and lifetime) with the previously reported 8-methoxypsoralen lens protein photoproduct seen in P-UVA-treated cataractous rat lenses. The data provide objective proof that these phototherapeutic drugs can generate specific P-UVA photoproducts in human lenses. Similar photoproducts have previously been demonstrated in experimental (rat) P-UVA cataracts.

Nuclear magnetic resonance analyses of the cold cataract: whole lens studies.

Pulse nuclear magnetic resonance (NMR) magnetization decay studies were performed on normal and cold cataractous rat lenses. Computer analyses of the decay curves have been interpreted to reflect two types of water within the lens that do not exchange rapidly. Upon lowering the temperature in the presence and absence of 5% acrylamide (a known agent that prevents the cold cataract phenomenon), significant differences in the relaxation rates of one water fraction were noted. 2H (NMR) spectra on young rabbit and human lenses showed temperature-related linewidth changes, which are significantly diminished in lenses incubated in acrylamide. 31P spectra also showed similar inorganic phosphate linewidth changes and also reflected progressive alterations in the metabolic state of these lenses. These studies demonstrate the potential of NMR methods for monitoring physicochemical parameters in the normal and cataractous mammalian lens.

Ocular phototoxicity and psoralen plus ultraviolet radiation (320-400 nm) therapy: an experimental and clinical evaluation.

The increase in fluorescent chromophores within the human ocular lens is age related, leading to an increasingly yellow core (nucleus) that presumably results from UV radiation exposure. In approximately 10% of our population this process progresses more rapidly, resulting in the formation of the brown (nuclear) cataract. Some lenticular discoloration may be beneficial, since it enables the mature lens to filter UV and short-wavelength visible radiation, thus protecting the retina from potential photodamage. Aphakic primate retinas can be irreversibly damaged by exposure to approximately 5 mW.cm-2 long-wavelength UV (greater than 325 nm) radiation. Photosensitized damage to the lens and retina with psoralen plus UV radiation (320-400 nm) (PUVA) has been demonstrated in experimental animals, and cataracts have recently been reported in patients given PUVA therapy. A new method to screen patients for lens damage is by enhanced fluorescence measurements. This method, UV slit-lamp densitography, permits detection of lenticular photodamage at a molecular level, years before visible opacities become manifest by conventional slit-lamp examination. This procedure has also demonstrated a significantly lower level of lens fluorescence (hence decreased filtering capacity) in patients with retinal degenerative diseases, suggesting UV photodamage as a factor in the progression and perhaps pathogenesis of these conditions.

8-methoxypsoralen and long ultraviolet effects on the rat lens: experiments with high dosage.

The effect of systemic 8-methoxypsoralen (8-MOP; 100 mg/kg daily) and subsequent long ultraviolet irradiation (UVA; 300 mJ/cm2; peak: 365 nm) on albino and pigmented rat eyes was studied in a 3-dimensional experimental set-up. While 8-MOP and UVA did not cause any ocular pathology when administered alone, a combined application of the two factors caused reversible corneal opacities, and irreversible iris devascularisation and cataracts. The irreversible changes were seen only in the albinos and accompanied by a significant decrease in lens wet weight. Phosphorescence and EPR spectroscopy demonstrated the formation of an 8-MOP-protein photoadduct in the animals treated with both 8-MOP and UVA. The results of this study emphasize the necessity of shielding the eyes of patients on photochemotherapy with protective spectacles.

[PUVA treatment and the problem of ocular damage (author's transl)]. / Die Photochemotherapie: Zur Frage ihrer Nebenwirkungen am Auge.

Recently, psoriasis has been shown to respond favorably to PUVA treatment, i.e., local or systemic therapy with a photosensitizer (e.g., 8-methoxypsoralen) and subsequent long UV irradiation. The possibility of this treatment damaging the eye is discussed in the light of various experimental results. As toxic changes only occur when photosensitizer and UVA act jointly, the eyes of PUVA-treated patients must be shielded from any ultraviolet exposure by UV-absorbing protective glasses with side shields. Such glasses should have no significant absorption in the visible range. The new Spectra Shield process enables lenses to be coated in such a way that virtually no UV or IR radiation is transmitted.