Light damage to the retina: an historical approach.

A brief review of retinal light damage is presented. Thermal damage requires a local rise in temperature of at least 10 °C, causing an instant denaturation of proteins. The primary absorber is melanin. Photochemical damage occurs at body temperature and involves cellular damage by reactive forms of oxygen. The photosensitizers are photoproducts of the visual pigments. First indications that non-thermal damage might exist, in particular in the case of eclipse blindness, was presented by Vos in 1962. Attribution thereof to photochemical action was presented in 1966 by Noell et al who also measured the first action spectrum, in rat. It turned out to be identical to the absorption spectrum of rhodopsin. However, in 1976 and 1982 Ham et al found a quite different spectrum in monkeys, peaking at short wavelengths. The latter spectrum, but not the former, was confirmed since in numerous publications with animal models including rat. In ophthalmological practice a 'sunburn' was at first the only complaint caused by light damage. To avoid this, patients with dilated pupils should always be advised to wear sunglasses. Since the invention of the laser accidents have been reported, the most recent development is youth playfully pointing a strong laser pen in their eyes with marked consequences. The operation microscope and endoilluminators should always be used as brief as possible to avoid photochemical damage. Arguments for implant lenses that block not only the UV but also part of the visible spectrum seem too weak to justify extra costs.

Retinal damage by optical radiation. An alternative to current, ACGIH-inspired guidelines.

BACKGROUND: The ACGIH guidelines for protection against retinal damage by optical radiation are often difficult to apply due to their lack of transparency. The less known guidelines by the Netherlands Health Council (HCN), dating from 1978 and updated in 1993, might offer a way out in many cases. METHODS: A comparison is made of these guidelines, embedded in a short sketch of the history. They are illustrated by examples of applications. RESULTS: In most cases the HCN guidelines produce results that hardly deviate from those obtained with the ACGIH guidelines but in some cases the results diverge and in other cases HCN gives an answer where ACGIH seems to fall short. CONCLUSIONS: The HCN guidelines form a good alternative to those of ACGIH.

Comparison of fluorescence of sodium fluorescein in retinal angiography with measurements in vitro.

To quantify dye leakage in ocular fluorescein angiography, the arterial concentration of sodium fluorescein has to be determined. We investigated whether the nonlinear relationship between the fluorescein concentration and the fluorescence intensity obtained by in vitro measurements corresponds with that measured in vivo in a retinal artery. The time series of fluorescence in a retinal artery were recorded using an in-house-designed and -built confocal scanning laser ophthalmoscope in 11 healthy volunteers. Three different doses of sodium fluorescein were injected successively. About 10 min after the last injection a venous blood sample was drawn. The three in vivo peak intensities were fitted by least squares on the in vitro calibration curve using the first peak concentration and an intensity scaling factor as the two unknown parameters. The fit showed that the saturation of the three in vivo peak intensities corresponded well with the in vitro data. Calculation of the intensity scaling factor from the blood sampling data confirmed the result of the fit. The fitted concentration was verified by showing that the cardiac output necessary to obtain this concentration was within the physiological range. The fluorescence measured in our in vitro experimental setup corresponded well with the in vivo measurements. Therefore, the results from in vitro measurements can be applied in the analysis of fluorescein angiograms.

Wavelength dependence of the Stiles-Crawford effect explained by perception of backscattered light from the choroid.

To explain the wavelength dependence of the directional sensitivity of human foveal cones (Stiles-Crawford I effect) we extended an existing fundus reflectance model for calculation of the total absorption by visual pigment. We took experimental data from literature for both the psychophysical and the optical Stiles-Crawford effect and optimized parameters to fit the experimental data. The wavelength dependence of the Stiles-Crawford effect could be well described with the geometrical optics model. Essential elements are self-screening and the inclusion of backscattered choroidal light for perception.

Endoillumination during vitrectomy and phototoxicity thresholds.

AIM: To assess the retinal phototoxicity hazards of and to provide safety margins for endoillumination during vitrectomy. METHODS: The absolute power and spectral distribution from various light sources and filter combinations that are commercially available for vitreous surgery were measured. The maximal exposure times based on the ICNIRP safety guidelines for photochemical and thermal injury of the aphakic eye were calculated. Additionally, the effect of various measures that reduce the risk of phototoxicity was evaluated. RESULTS: Measurements of the spectrum and energy indicated that the ICNIRP safety guidelines for photochemical retinal damage are exceeded within 1 minute for nine out of 10 combinations tested. With an additional 475 nm long pass filter, light levels below 10 mW, and a distance from light probe to retina of at least 10 mm, the allowable exposure time can be increased up to 13 minutes. Thermal damage can be anticipated when the light probe touches the retina. CONCLUSION: Commercially available light sources for endoillumination during vitrectomy are not safe with respect to photochemical retinal damage. Even with maximal precautions macular phototoxic damage remains a factual danger during vitrectomy.

Influence of lutein supplementation on macular pigment, assessed with two objective techniques.

PURPOSE: Macular pigment (MP) may protect against age-related macular degeneration. This study was conducted to determine the extent of changes in the macular pigment density as a consequence of oral supplementation with lutein. A second purpose was to compare two objective measurement techniques. METHODS: In the first technique, reflectance maps were made with a scanning laser ophthalmoscope. Digital subtraction of log reflectance maps and comparison between the foveal area and a 14 degrees temporal site provided MP density estimates. In the second technique, spectral fundus reflectance of the fovea was measured with a fundus reflectometer and analyzed with a detailed optical model, to arrive at MP density values. Eight subjects participated in this study. They took 10 mg lutein per day for 12 weeks. Plasma lutein concentration was measured at 4-week intervals. RESULTS: After 4 weeks, mean blood level of lutein had increased from 0.18 to 0.90 microM. It stayed at this level throughout the intake period and declined to 0.28 microM 4 weeks after termination. Measurement of the density of MP showed a within-subject variation of 10% with MP maps and 17% with spectral reflectance analysis. MP density showed a mean linear 4-week increase of 5.3% (P: < 0.001) and 4.1% (P: = 0. 022), respectively. CONCLUSIONS: Supplementation with lutein significantly increased the density of the MP. Analyzing reflectance maps with a scanning laser ophthalmoscope provided very reliable estimates of MP.

Hold up of dye in the arm during fluorescein angiography: a quantitative demonstration.

PURPOSE: To demonstrate a hold-up of part of the fluorescein bolus in the arm as a result of arm position. METHOD: Case report. We obtained a fluorescein angiogram with a calibrated confocal scanning laser ophthalmoscope in a 20-year-old healthy subject. During and after injection, the upper arm was held in approximately 60 degrees abduction, 65 degrees exorotation, and slight anteflexion. In the late venous phase, the subject moved the upper arm on the injected side to a more neutral, downward position. RESULTS: We measured a distinct rise in fluorescence level about 10 seconds after movement of the arm. The most likely explanation is relief of a partial obstruction of the venous drainage, which had been caused by the position of the upper arm described above. CONCLUSION: Impaired venous drainage of the injected arm caused by exorotation and abduction of the upper arm is a potentially common cause of delayed dye arrival or unexpectedly reduced contrast level during fluorescein angiography. Therefore, arm position needs attention in fluorescein angiography.

Slow optical changes in human photoreceptors induced by light.

PURPOSE: The basic assumption of fundus reflection densitometry is that changes in reflectance are solely determined by photolysis and regenerating visual pigments. This study was undertaken to investigate small but systematic deviations from this rule. METHODS: Spectral reflectance changes (450-740 nm) of the fovea were measured during light and dark adaptation over a period of 66 minutes in five healthy subjects. The directional properties of the fundus reflection were examined with a custom-built scanning laser ophthalmoscope (SLO) at 514, 633, and 790 nm. The same instrument was also used to find the spatial distribution of the reflectance changes. RESULTS: In addition to fast changes consistent with visual pigment, slower reflectance changes (lasting 10-20 minutes) were observed at all wavelengths including 740 nm. Because visual pigment does not absorb at 740 nm, a second mechanism must be involved. Factor analysis generated two factors (i.e., spectral curves) that explained more than 97% of the variations in the time course of the spectral reflectance. Total reflectance was modeled by means of an existing model for fundus reflection, and it was found that the first factor strongly resembled the rapid changes in absorption of the cone pigments. The second factor seems linked to slow changes in cone reflectance. Measurements with the SLO showed a clear increase in directionally dependent reflectance from 6 to 30 minutes in the dark. This was observed only in the central 6 degrees of the retina. CONCLUSIONS: The characteristics of the slow reflectance changes all point to the cone photoreceptors as the origin. Most likely, alterations in the index of refraction between the interphotoreceptor matrix and photoreceptors lie at the base of this hitherto unknown phenomenon.

The effects of two stereoisomers of N-acetylcysteine on photochemical damage by UVA and blue light in rat retina.

High doses of light can cause damage to the retina, e.g. during intraocular surgery. Previously, thiols have been demonstrated to protect against retinal damage in various damage models. Such protection is very promising for clinical practice. Retinal light damage can be caused by a relatively short exposure to high irradiance levels. These conditions occur during intraocular surgery. In the current study we therefore investigated whether the thiol N-acetylcysteine protects against retinal light damage under high irradiance conditions in the rat retina. Two stereoisomers of this thiol were tested for protection against two spectrally defined types of retinal light damage. Shortly after administration N-acetyl-L-cysteine in doses of 270-1000 mg/kg intraperitoneally protected against 380 nm (UVA) light but not against 470 nm (blue) light. Two hours after injection the protection had diminished. We observed no protection by the stereoisomer N-acetyl-D-cysteine. From this study we conclude that N-acetyl-L-cysteine protects stereospecifically against retinal damage in the UV but not in the visible part of the spectrum. This limits the possible applications.

Temporal sequence of changes in rat retina after UV-A and blue light exposure.

Two spectral types of retinal light damage were induced in pigmented rats by irradiating small retinal patches at either 380 or 470 nm. The temporal sequence of changes in the retina was followed for up to 2 months by funduscopy and histology. For both damage types, fundus changes were best visible after 3 days. Histology showed that 380 nm specifically damaged photoreceptor cells, particularly the rods. All cell compartments of the rods, including the nucleus were affected already after 3 h. In the next days, damaged rods degenerated. At high doses (2.5 x the funduscopic threshold dose) all rods in the irradiated area were lost, resulting in a local photoreceptor lesion, which was still present at 2 months after the irradiation. At 470 nm, damage occurred both in the photoreceptor layer and in the pigment epithelium. Acute changes, at 1 h after irradiation, consisted mainly of damaged mitochondria in these layers. Next, the pigment epithelium showed swelling, an altered melanin distribution and, at high doses (2.5 x threshold), interruptions of the monolayer. Degeneration of photoreceptor cells was initially limited to a few scattered cells, but 3 days after high doses focal areas of massive degeneration were seen. At late stages, the cells of the pigment epithelium recovered and the photoreceptor layer showed a loss of cells. The results show that the spectral damage types are distinct in the early phases, indicating that different mechanisms are involved. Yet, the end effect of both damage types after exposure at doses up to 2.5 x the funduscopic threshold is remarkably similar and consists of local photoreceptor lesions.

Filling-in after focal loss of photoreceptors in rat retina.

We investigated the fate of isolated photoreceptor lesions in rat retina over a time span of 6 months. With a carefully selected dose of UV-A (380 nm) a complete loss of photoreceptors was caused in sharply demarcated areas of 200, 400 or 800 microm wide, without visible damage to other retinal layers. One day after irradiation, all rods were pyknotic. Three weeks later practically all damaged photoreceptors were removed. The size of the lesion had decreased as the surrounding photoreceptors had migrated into the lesion. The outer segment tips had moved inwards up to 200 microm, but the innermost nuclei in the outer nuclear layer had moved inwards substantially less. The distance over which the photoreceptors migrated increased with lesion size, but only 200 microm defects were filled-in completely on the level of the outer segments. Between three weeks and six months after irradiation, no further decrease in lesion size occurred. We conclude that after local loss of photoreceptor cells the bordering photoreceptors rapidly shift into the lesion area, but complete filling-in is limited to very small lesions.

[The laser pointer: no demonstrated danger to the eyes]. / De laserpen als aanwijsstok niet aangetoond gevaarlijk voor de ogen.

If laser pointers are powerful enough (> 5 mW), they can cause ocular damage. Most laser pointers in use, however, have low power, viz. 1 mW. In the peer-reviewed scientific literature worldwide not a single case of eye damage due to laser pointers is described. A review among Dutch ophthalmologists up to June 1998 revealed no cases of permanent damage caused by laser pointers. In view of the widespread use of laser pointers, the risk of retinal damage must be minimal, even with the types now banned. Laser pointers of 1 mW emitting light red or green light have sufficient visibility on projection screens. It is advisable to prohibit the sale of more powerful pointers to prevent excesses.

A comparison of the optical Stiles-Crawford effect and retinal densitometry in a clinical setting.

PURPOSE: To compare the measurement of the optical Stiles-Crawford effect (SCE) to the densitometry of cone visual pigments in a clinical setting. Both tests provide information on outer retinal integrity, but the optical SCE can be performed in far less time. METHODS: Images acquired with a custom-built scanning laser ophthalmoscope were used to assess visual pigment density and optical SCE. Visual pigment density was regarded as the "gold standard." More than 100 patients with suspected, and some with known, outer retinal pathology were tested. The group included cases of central serous detachment, cone dystrophy, Stargardt's disease, Best's disease, and retinitis pigmentosa. RESULTS: Parameters of the optical SCE of 25 healthy subjects and 106 patients were taken through a stepwise linear regression to predict density. The correlation between predicted density from the optical SCE and the measured density was 0.82. The sensitivity of the optical SCE to detect decreased density was 96%. When only the foveal reflectance was considered, sensitivity was still 84% CONCLUSIONS: The optical SCE is a sensitive and fast method for detecting cone photoreceptor disturbances.

Two spectral types of retinal light damage occur in albino as well as in pigmented rat: no essential role for melanin.

Earlier we showed that two spectral types of retinal damage occur in the pigmented rat. In the present study we investigated whether the same is true for albino rats. When investigating this issue we implicitly investigated the role of melanin in both damage types. An albinotic (Wistar) and a pigmented (Long Evans) strain of rats were used. Under anesthesia, a small part of the retina was irradiated at either 380 nm or at 470 nm. Three days later, the retina was analysed by funduscopy and prepared for light microscopy. Funduscopy showed no signs of damage in the albinotic retina. In the pigmented retina a decoloration of the fundus was noticed after irradiations starting from retinal doses of 0.6+/-0.1 J cm-2 at 380 nm, and from 489+/-71 J cm-2 at 470 nm. By light microscopy, retinal damage was found in the albino retina. The histologic manifestations at 380 nm differed from those at 470 nm. Irradiation at 380 nm at a dose of 0. 5-0.9 J cm-2 damaged a few scattered photoreceptor cells. At doses of 1.2-1.6 J cm-2 all rods were damaged, while the other retinal layers showed no changes. These findings were similar to those found at 380 nm in the pigmented rat. At 470 nm, damage was found most prominently in the retinal pigment epithelium. These cells showed swelling and an increased number of dark inclusions. Threshold damage occurred at doses of 250-500 J cm-2. Again, the pathology in the pigmented rat was highly similar to that in the albino rat. The results show that both spectral damage types occur in albino as well as in pigmented retina. Therefore, melanin plays no crucial role in these light damage types.

On the Stiles-Crawford effect with age.

PURPOSE: To determine whether the Stiles-Crawford effect remains stable after subjects have aged 30 years. METHODS: The relative luminous efficiency as a function of pupil position (Stiles-Crawford effect) was determined for the same seven subjects on the same apparatus in the 1960s and in 1995. The pupil opening was traversed nine times, at 20 degrees azimuth intervals. Data were fit with a revolution paraboloid yielding a peak position (x0, y0) and a peakedness (rho). RESULTS: Two of seven subjects showed a significant, but small, decrease in rho, and the other five showed, no change. No clear outcome in x0, y0 changes could be reported because of differences in pupil dilation then and now. CONCLUSIONS: Although exceptions are found on the stability of the Stiles-Crawford effect with age, the authors can still conclude that it is stable.

Effect of body temperature on retinal damage by 488 nm light in rat.

Retinal light damage is influenced by the body temperature during exposure, but previous studies do not agree on the magnitude of the effect. A study in rats with broadband green light reported a much larger effect than a study with 380 nm light. The present study set out to clarify whether the spectral composition of the damaging light is responsible for this discrepancy by using 488 nm instead of 380 nm light. Wavelengths in the range of 470-550 nm are known to produce a different damage type than 380 nm. Small patches of retina of anesthetized rats were exposed to 488 nm radiation of an argon ion laser. Body temperature was varied between 30 and 40.5 degrees C. Three days after irradiation, the retina was inspected by funduscopy and prepared for light microscopy. The dose of radiation needed for a just visible change in fundo decreased by 6% per degree increase in body temperature. Damage was mainly found in the retinal pigment epithelium. Temperature had no effect on damage morphology. The temperature effect at 488 nm is much smaller than reported for broadband green light. We conclude that the spectral composition of the damaging light is not responsible for the discrepancy on the magnitude of the temperature effect. Other differences between the studies must be responsible, such as difference in retinal irradiance levels.