Long-term Hazards of Neonatal Blue-Light Phototherapy

J. Oláh; E. Tóth-Molnár; L. Kemény; Z. Csoma

Disclosures

The British Journal of Dermatology. 2013;169(2):243-249. 

In This Article

Neonatal Blue-Light Phototherapy and the Neonatal Eye

It has long been known that BL can induce retinal photoreceptor degeneration in rats and in mammals.[23,24] Experimental results outlining the potentially retinotoxic effect of BL continue to accumulate. In general, the outer photoreceptor segments are the structures that are first injured, and this is followed by damage to the retinal pigment epithelial cells.[25] Widespread apoptotic cell death has been demonstrated in the albino rat retina after BL illumination.[26] A very similar effect observed in BL-irradiated, cultured human retinal pigment epithelial cells could be prevented through use of a blue-blocking filter.[27–29] These effects might be due to BL having a considerable capacity to remove electrons from molecules, resulting in reactive oxygen species. This photoelectric effect in the 400–500 nm interval has its peak at 440 nm and is referred to as the BL hazard.

There have been previous surveys of the possibility of exposure to BL eliciting the malignant transformation of uveal melanocytes (Fig. 4). Manning et al.[30] found that long-term exposure to fluorescent BL resulted in the development of uveal epithelioid melanoma in rats. In another experimental animal model, Di Cesare et al.[31] observed that exposure to BL led to a significantly higher rate of proliferation of human uveal melanoma cells relative to the unexposed, control group. The in vitro model utilized by Marshall et al.[32] revealed that exposure to BL induced a significant increase in the rate of proliferation of four different human uveal melanoma cell lines.

Figure 4.

Blue-light exposure of cutaneous and uveal melanocytes during phototherapy. Ocular melanocytes consist of two different cell types: conjunctival and uveal melanocytes. Uveal melanocytes reside in the middle layer of the eyeball: in the iris, the ciliary body and the choroid. Conjunctival melanocytes are located in the conjunctiva (thin layers of epithelium and underlying connective tissue covering the anterior surface of the sclera and the posterior surface of the eyelids).

There are a number of factors that may influence the extent to which the retinal pigment epithelial cells and photoreceptors are damaged. The spectral composition, duration, intermittence and intensity of the radiation, and the light transmittance characteristics of the given structures, besides interindividual variations, can all influence the degree of biological damage.[33]

The amount of radiation reaching different ocular structures additionally depends on the transmission profile of the ocular media. The cornea effectively filters UV radiation below 295 nm and transmits most of the UVA and UVB and visible spectrum throughout life, with merely a relatively minor reduction in percentage transmission in the elderly.[34] Transmittance increases rapidly above 300 nm, reaching > 90% above 500 nm. The characteristics of the light transmission of the crystalline lens are highly age dependent. Whereas in neonates the lens transmits > 90% of the light with wavelengths below 450 nm, this declines to < 20% by 80 years of age due to the progressive accumulation of lenticular chromatophores.[35–37]

Our twin study demonstrated that NBLP was associated with a substantially higher prevalence of benign ocular pigmented lesions.[16] The number of melanocytic lesions of the iris in our study proved to be independent of age. This can be explained by the time course of iris pigmentation: the melanin concentration peaks during early childhood, thereafter usually remaining constant throughout life unless affected by certain ocular disorders, which can lead to hypopigmentation or hyperpigmentation.[38,39]

In contrast with cutaneous MN and cutaneous melanoma, only inconsistent data are available regarding both the factors that may influence the formation of uveal pigmented lesions and the role of benign pigmented ocular lesions as melanoma risk indicators. Nordlund et al. and Albert et al.[40,41] reported that the total number of iris naevi was significantly higher in patients with cutaneous melanoma than in controls. Weis et al.[15] recently published a meta-analysis that supports the correlation of uveal melanoma with CAMNs, CMNs and iris naevi. We earlier found a substantially higher prevalence of ocular pigmented findings (conjunctival and uveal naevi) in patients with dysplastic naevus syndrome compared with dysplastic naevus-free volunteers.[42] In another study, we observed an increased rate of cutaneous dysplastic naevi in patients with uveal melanoma or with cutaneous melanoma. The relative risks of uveal melanoma and cutaneous melanoma in patients bearing atypical moles proved to be 4·36 and 4·22, respectively.[43] Our investigations have additionally revealed that the presence of cutaneous dysplastic naevi in patients with uveal melanoma is associated with higher proportions of the prognostically worst forms of uveal melanoma.[44]

The ocular media of neonates are highly transmissive relative to those of adults, especially in the blue and UV regions of the spectrum. In the course of NBLP, the eyes are routinely patched or shielded with phototherapy hoods in order to exclude ocular exposure.[45,46] Such protective measurements can exclude > 90% of the light emitted by phototherapy sources, but accidental exposure may occur.[47,48] In one study, the eye shields were displaced in over half of all observations.[49] On the other hand, precise patching of an infant's eye may be of secondary importance in comparison with more immediate and potentially life-preserving interventions. Although the potential hazard of BL is alleviated by the fact that neonates tend to keep their eyes shut in bright light, it is known that light in the visible spectrum penetrates the skin. The level of BL transmission through the closed eyelids of infants cannot be assessed with accuracy. The peak transmission is at the red end of the spectrum, and approximately 14% of the light at this wavelength can be transmitted in the adult, and 21% in the preterm infant.[50,51] It has been estimated that at both ages around 3% of the light with wavelengths below 580 nm can pass through the eyelid. Light does not enter the eye exclusively through the pupil, as the sclera and choroid also transmit about 14% of the light falling on them, but it does predominantly at the red end of the spectrum. With regard to the light transmissibility profile of the neonatal eye, which allows the penetration of an appreciable amount of potentially harmful light into the eye, further studies are needed to clarify the possible long-term effects of neonatal BL exposure on the melanocytic proliferation of the uveal tract.[37,52] In the event of unavoidable phototherapy treatment, alternative methods of eye protection should be used in order to minimize accidental BL exposure of the extremely vulnerable neonatal eye.

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