Retinal damage produced by intraocular fiber optic light.

We exposed the maculas of owl monkey eyes to light from an intraocular fiber optic light source similar to that used for human pars plana vitrectomy. Retinal irradiance was calculated at 0.22 W/cm2. Eyes were exposed for time intervals ranging from 30 minutes to five minutes and were observed after light treatment by fundus photography and fluorescein angiography. Tissue was obtained for light and electron microscopy by animal killing at one hour, 24 hours, one week, and four weeks. Fundus lesions were seen ophthalmoscopically as early as five hours following 30 minutes of light exposure. Significant damage to the photoreceptor layer and less damage to the pigment epithelium was present by light and electron microscopy as early as one hour after 30 minutes of light exposure. By one month complete loss of photoreceptors with Müller cell junctions between inner retina and flattened abnormal retinal pigment epithelium cells was observed. Fluorescein angiography revealed significant staining of the pigment epithelium and outer retina 24 hours after 30 minutes of light exposure. No leakage from retinal vessels occurred. At one month following light treatment, transmission of choroidal fluorescein through window defects in the pigment epithelium was present with no retinal staining. The threshold for ophthalmoscopically visible fundus lesions in this study was 15 minutes of light exposure. Ten minutes of light treatment was the threshold for microscopic changes. Short light exposures damaged the outer retina and spared the pigment epithelium. Removing a substantial amount of the infrared light from our light source did not protect the retina from damage. Removal of light between 400 and 500 nm is probably more helpful in protecting the retina. Intermittent light exposure of the retina seemed as harmful as uninterrupted illumination for the same cumulative period of time. We speculate that the retinal damage caused by intraocular fiber optic light has primarily a photic mechanism. Damage to the retinal pigment epithelium may be secondary to outer retinal damage. The present levels of intraocular light used for human pars plana vitrectomy are probably safe in most instances. Lengthy preretinal membrane stripping procedures during vitrectomy, however, may pose a threat of light damage to the retina. This damage must be appreciated as continued efforts are made to produce brighter sources of intraocular light for human pars plana vitrectomy.     

New approach to evaluate retinal protection by intraocular lenses against age-related lipofuscin accumulation-mediated retinal phototoxicity

PURPOSE: To present a new approach for evaluating intraocular lenses (IOLs) for retinal protection from age-related lipofuscin accumulation-mediated phototoxicity. SETTING: Alcon Laboratories Inc., Fort Worth, Texas, USA, and Cardiff University, Cardiff, United Kingdom. METHODS: Age-related lipofuscin accumulation-mediated action spectra for retinal phototoxicity in an aphakic eye were created for this evaluation. Transmission curves for 6 IOLs and for cornea and spectral radiant power distribution for sunlight and 2 lamps were used. Pseudophakic action spectra and retinal phototoxicity for 3 wavelength ranges and 3 ages were computed. The percentage protection of each IOL was computed as the reduction in phototoxicity relative to the aphakic eye. RESULTS: Retinal phototoxicity increased 3.66 times from the third to ninth decade of age. The comparative retinal phototoxicity and retinal protection provided by IOLs were dependent on the light source and range of wavelength; however, unlike phototoxicity, retinal protection was independent of age. The 420 to 480 nm range was the most useful for discriminating protection by IOLs. CONCLUSIONS: Retinal phototoxicity significantly increased with age; however, the retinal protection by IOLs was independent of age. The interaction between the transmission curve of IOLs and light sources required inclusion of widely used lamps besides sunlight for evaluation of IOLs. For the 420 to 480 nm wavelength range, the 3 light sources clearly discriminated the protection provided by IOLs. The AcrySof Natural IOL (Alcon) provided the highest protection consistently for the tested light sources.     

Optical coherence tomography and macular phototoxicity

CASE REPORT: Ocular examinations and optical coherence tomography (OCT) were performed in three patients with retinal phototoxicity lesions. Fluorescein angiography depicted a window defect. OCT exhibited hyporeflectivity at the outer foveal retina and fragmentation of the inner reflective layers, corresponding to the junction between the inner and outer photoreceptor segments. DISCUSSION: Retinal damage after light exposure has a rapid onset and shows different patterns in OCT examination. OCT findings suggest that decreased visual acuity may be associated with full-thickness photoreceptors and retinal pigment epithelium (RPE) involvement. OCT is a useful tool for objective assessment of retinal pathology in phototoxicity cases where fundus changes may be minimal or absent.     

Exposure to a solar eclipse causes neuronal death in the retina

BACKGROUND: A solar eclipse was observed in Europe on 11 August 1999. Several individuals suffered from transient or persisting retinal damage, caused by gazing at the eclipse without adequate eye protection. Retinal damage is the most serious hazard of exposure to light. but the mechanisms by which this type of exposure produces retinal damage and its cellular correlates are not yet established. We used an animal model to monitor the mechanisms of retinal damage following excessive light exposure, and in particular to study whether observation of the eclipse induces death of retinal cells. METHODS: In the geographic area where the experiment was conducted, a partial (90%) solar eclipse was observed. Experimental albino rats were exposed to these eclipse conditions, and control rats were exposed to normal sunlight. Another group of control animals was exposed to the same conditions, but was provided with protective light filters of the type recommended for human use. The DNA fragmentation in retinal sections of the various groups was analysed by terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labelling. This analysis revealed that exposure to both normal sunlight and to the eclipse resulted in neuronal apoptosis. Immunohistochemical techniques were used to evaluate possible glial-vascular alterations. RESULTS: Dying cells could first be detected 24 h after exposure, the largest number of which were found 6 days later in the photoreceptor layer. Control levels were attained 14 days after the exposure. Retinal ganglion cells underwent apoptosis in both groups (normal sunlight and eclipse exposure), whereas in the neuroglial cells there was an up-regulation of the intermediate filament content. The number of dying cells in both groups was greater in animals whose pupils had been dilated pharmacologically during exposure. On the other hand, the protective filters were effective in preserving the rat retinal cells from apoptosis. CONCLUSIONS: These results show, for the first time, that the cellular correlates of solar retinopathy are neuronal apoptosis accompanied by glio-vascular responses. Cellular apoptosis is an irreversible process, which could manifest itself as permanent visual impairment. The activation of non-neuronal cells, such as glial and endothelial cells, could be responsible for the more transient clinical symptoms.     

Effect of continuous versus multiple intermittent light exposures on rat retina

The damaging effects of continuous light exposure to the albino rat retina have been well documented. However, the cumulative effects of multiple light exposures are not well defined. We therefore compared the retinal injury induced by a single 24 hour light exposure with that caused by three intermittent exposures of 8 hours each. Eight dark-adapted albino Lewis rats were exposed for 24 hours to green fluorescent light (490-580 nm) at an illuminance level of 175 foot-candles. A second group of 8 rats was exposed under similar conditions in three split doses of 8 hours each at intervals of 7 days between each exposure. Recovery was allowed in total darkness, and the animals were sacrificed 2 weeks following the last exposure. Retinal damage was assessed by morphometry and light and electron microscopy. Mild cumulative retinal injury, mostly in photoreceptor cells with relative sparing of the retinal pigment epithelium, was seen in the split dose group, while extensive damage involving photoreceptor cells and retinal pigment epithelium was noted in the group exposed continuously for 24 hours.     

Light and the developing retina

Retinopathy of prematurity (ROP) has increased in the United States in the past decade. Its resurgence has been attributed to advances in medical care which have increased the survival of infants less than 1000g. Retinal immaturity and exposure to supplementary oxygen are generally accepted as the principal factors associated with ROP, however precocious exposure of the immature retina to light may also contribute. The preterm infant is routinely exposed for the duration of hospital stay to bright continuous light at levels which produce retinal damage in animals. A recent study has provided evidence implicating light in ROP. Preterm infants for whom the light levels were reduced had a lower incidence of ROP, compared to a similar group of preterms exposed to standard levels of nursery light. Given the problems of a non-randomized design, the results must be considered preliminary; however the findings are substantiated by parallel results in both hospitals studied and by an effect of exposure to light within the treatment group. Speculations regarding the mechanisms of light as a contributor to ROP include: alterations of retinal metabolism, cellular damage by phototoxicity, and the generation of free radicals. Mechanisms of phototoxicity are compatible with theories of oxygen toxicity. Light may not be necessary for ROP to occur, but it may increase the risk.     

Temperature-dependent light damage to the retina

We examined the ability of hypothermic infusion fluid to reduce the risk of light damage to the retina from the intraocular fiberoptic probe during vitreous surgery. Following vitrectomy, we exposed the retina of rabbits to light from an intraocular fiberoptic probe during infusion of fluid at body temperature (39 C) and compared this with exposures during infusion of room temperature fluid (22 C). Retinal irradiance was 0.33 W/cm2. Damage was determined ophthalmoscopically and histologically. Cooling the infusion fluid from body to room temperature extended the damage threshold from approximately 25 to 60 minutes. A 35-minute exposure to body temperature fluid was compared with the same exposure during infusion of room temperature fluid. While retinal and retinal pigment epithelium damage was present after the body temperature exposure, no damage was detected after the room temperature exposure. Vitreoretinal surgeons should avoid warming intraocular infusion fluids to levels above room temperature.     

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.     

Light-induced maculopathy in cataract surgery

CASE REPORT: Case 1: An 82-year-old man who underwent an uncomplicated phacoemulsification and IOL implantation (Tecnis Z 9000 lens) in his right eye under topical anaesthesia. Surgery lasted 14 minutes. Case 2: A 60-year-old woman with bilateral advanced primary open angle glaucoma who underwent an uncomplicated phacoemulsification and IOL implantation (Tecnis Z 9000 lens) in her right eye under peribulbar anaesthesia. Surgery lasted 36 minutes. One month after surgery both patients noted a para-central scotoma and impaired vision. Fluorescein angiography in both cases revealed retinal pigment epithelial changes compatible with intra-operative light-induced maculopathy. DISCUSSION: Light-induced maculopathy has been reported following cataract surgery. Whether physical properties of these new polysiloxane lenses contribute to retinal susceptibility to phototoxicity under certain light conditions needs to be elucidated.     

Retinal damage from light.

Exposure of a monkey retina to the light from a slit lamp for 40 minutes produced a visible retinal change that disappeared after four weeks. Exposures of 20, ten, and five minutes produced no visible changes. Extensive retinal damage was produced in the macula of the other eye of the monkey by a one-hour exposure to the light from an operation microscope. This damage was almost unchanged one year later. Exposure of the monkey retina from the same operation microscope, for the same length of time, with the blue light filtered out, produced a much smaller lesion that, after one year, could not be seen visibly but was detected with fluorescein angiography.     

Transcleral contact krypton-laser photocoagulation of the retina in rabbits.

Transcleral contact retinal krypton laser photocoagulation of the retina was studied in rabbit eyes. The laser application was performed under indirect ophthalmoscope visual control with indentation of the sclera by the laser probe. Retinal lesions were produced with powers ranging from 0.2 to 0.3 W and application times between 1 and 2 sec. The lesions were studied histologically 2, 5, 10, 12, 20, 30 and 70 days after treatment. Histopathological examination of the lesions showed damage of mainly the outer retinal layers in light lesions, and to all layers of the retina in the more intense lesions. No scleral damage was observed in the light lesions, whereas transient oedema of the inner sclera was seen in the intense lesions. Studies with enucleated rabbit eyes showed that indentation of the sclera by the laser probe substantially decreased the power needed to produce a retinal lesion. It is concluded, that when used with scleral indentation, transscleral krypton laser photocoagulation of the retina can be performed with minimal damage to the sclera.     

兔视网膜光损伤模型的建立

目的建立和研究视网膜光损伤动物模型,观察手术显微镜致兔眼视网膜光损伤的病理变化。方法将健康灰兔8只随机分为对照组、光损伤组,每组4只。所有实验动物均在循环光环境适应7d,光照前暗适应24h。实验前,散大瞳孔至8mm左右。光损伤组光照（14500lux）30min,暗适应30min。光照48h后取材制成超薄切片,电镜观察。对照组散瞳后不予光照,相应时间取材观察。结果对照组视网膜组织结构清楚,细胞形态规整。光损伤组光感受器外节膜盘崩解非常明显,外核层细胞排列紊乱,核固缩。色素上皮层核染色质边集,呈现细胞凋亡的早期改变,线粒体空泡变性。结论手术显微镜（14500lux）可诱导兔视网膜光损伤,病理特点是光感受器的退行性改变。     

Light-induced retinal damage in mice. Hydrogen peroxide production and superoxide dismutase activity in retina.

The oxidative mechanism in retinal damage due to exposure to intense light was investigated histochemically and biochemically. SMA mice (albino mice) of 2 to 3 months of age were exposed to intense light (1000-1400 lux). In the cyclic light-reared group (without dark adaptation), the outer and inner segments of the photoreceptor cells were damaged after 3 days of exposure, and severe outer nuclear layer damage was observed after 5 to 7 days of exposure. Hydrogen peroxide (H2O2) production in the outer nuclear layer increased with the progress of retinal damage. In the dark-reared group (dark adaptation of 16-18 hours), outer and inner segment damage was noted after 4 hours of light exposure, and severe outer nuclear layer damage was noted after 12 hours of light exposure. H2O2 production increased in the outer nuclear layer with retinal damage. Superoxide dismutase (SOD) activity did not change before the occurrence of retinal damage, and decreased by 25% after 3 days of exposure to light in the cyclic light-reared group. The decrease in total SOD activity corresponded to that of manganese-SOD (Mn-SOD). In the dark-reared group, SOD activity did not change, even after 1 day of exposure. There appears to be some relationship between retinal light damage and H2O2 production in the outer nuclear layer. Superoxide dismutase activity failed to provide protection against retinal oxidative damage due to intense light exposure.     

Macular phototoxicity caused by fiberoptic endoillumination during pars plana vitrectomy.

Three cases of retinal phototoxicity were caused by light from the endoilluminator used in vitrectomy. Preoperative clinical examination, color photography, and fluorescein angiography in all three cases failed to disclose retinal pigment epithelial changes. Postoperative clinical findings, photographs, and fluorescein angiograms are highly suggestive of the presence of retinal phototoxicity. The characteristics of these lesions and surgical conditions implicate the endoilluminator as the source of photic injury. The macular lesions were noted within one week of the surgical procedure, measured between 2 and 5 disk diameters in size, involved the fovea in two eyes, and resulted in marked decrease in visual acuity in two of three eyes, with persistence in one eye. Initially, whitening of the outer retina was present, but was replaced by pigmentary mottling at the level of the retinal pigment epithelium within a few weeks. Preventive measures to avoid macular phototoxicity associated with vitrectomy are discussed.     

Incidental retinal phototoxicity associated with ingestion of photosensitizing drugs

BACKGROUND: to report on the possible correlation between incident retinal phototoxicity and the use of photosensitizing drugs. METHODS: four patients were examined because of scotomas and visual loss after an incidental exposure to a strong light source. One patient (two eyes) was exposed to standard camera flash; one patient (one eye) had a brief exposure to welding light; one patient (two eyes) underwent uncomplicated phacoemulsifications with intraocular lens implantation. The fourth patient had a severe retinal phototoxicity following a secondary intraocular lens implantation. All four patients underwent a thorough assessment including history of systemic drug use. These patients had ophthalmologic evaluation including: best corrected visual acuity (ETDRS charts), fundus examination, fluorescein and indocyanine green angiographies and were followed for 1 year. RESULTS: on presentation, the mean visual acuity was 7.5/20 (range: 20/400-20/20). Fundus examination disclosed yellow-gray sub-retinal lesions in all affected eyes. Early phase fluorescein angiography showed one or multiple hypofluorescent spots surrounded by a halo of hyperfluorescent window defect. In the late phase, some of these spots leaked the fluorescein dye. Indocyanine green angiography demonstrated hypofluorescent spots throughout with ill-defined borders of hyperfluorescence observed during the late stages. The common finding in these four patients was the fact that they were all taking one or more photosensitizing drugs (hydrochlorothiazide, furosemide, allopurinol, and benzodiazepines). Three of the patients had a full visual recovery a few months after the phototoxicity. The fourth patient remained with a visual acuity of 20/60 12 months after the light exposure. Despite the visual recovery, non-homogeneous retinal pigment epithelial disturbances persisted in all affected eyes. CONCLUSION: phototoxicity following incidental light exposure may occur in patients taking drugs of photosensitizing potential. Therefore, the thorough history of systemic drug ingestion should be obtained if patients have exposure to strong light sources.     

Phototoxicity. The eclipse filter

In conjunction with ultraviolet filtration and to further minimize the risk of phototoxic retinal damage during anterior segment surgery, the operation microscope has been modified to eliminate on demand all light entering the eye by eclipsing the pupil when the red reflex is not required. Retinal light exposure may be reduced as much as 75%.     

Effect of UVA on biosynthesis of melatonin in the retina

No difference in the retinal acetylserotonin-methyltransferase was found in two groups of quail which were exposed to irradiation of 0.1 W/m2 with green and blue light respectively for 1 hour. Decreased retinal enzyme activities (isoelectric point pH 5.0) were observed in response to exposure to green and UVA light concomitantly with increased irradiation. Retinal enzyme activity in response to blue light was lower than in response to UVA light (0.1 W/m2). Although exposure to UVA light affects the visual process only slightly, melatonin biosynthesis was shown to be influenced significantly. Since melatonin is said to play an important role in light adaptation processes, it may be suggested that an imbalance between visual process and light adaptation may occur, predominantly in the aphakic eye.     

Evidence against melanin as the mediator of retinal phototoxicity by short-wavelength light.

Albino and pigmented (black-hooded) rats of the Sprague-Dawley and Long Evans strains, respectively, were compared in terms of their susceptibility to retinal damage by ultraviolet-A light. Anesthetized animals were exposed to ultraviolet-A light (lambda max = 360 nm) for 4 hr and retinal damage was assessed 1 week later by electroretinographic analysis and measurement of outer nuclear layer thickness. Albino and pigmented animals showed approximately the same severity of ultraviolet-A retinal damage as a function of exposure irradiance. Furthermore, both pigmentation strains showed swelling and vesiculation of rod inner segment mitochondria as an early manifestation of damage. An abbreviated study on a congenic rat strain (F344-c/+) of albino and pigmented littermates again demonstrated an equal susceptibility to ultraviolet-A phototoxicity for both pigmentation phenotypes. These findings provide evidence that melanin is not the mediator of short-wavelength phototoxicity to the retina, since damage readily occurred in albino animals completely lacking this chromophore.     

Electrophysiologic evaluation of retinal pigment epithelial damage induced by photic exposure

PURPOSE: To evaluate the retinal pigment epithelial damage induced by light exposure. METHODS: One eye of 20 rabbits was exposed to xenon light for 2 hours at an irradiance of 140 mW/cm2 at the surface of the cornea. The contralateral eye served as a control. Forty-eight hours after the light exposure, corneal direct-coupled electroretinograms and the 7% NaHCO3 (bicarbonate) responses of the standing potential were recorded. RESULTS: The amplitudes of the a-, b-, and c-waves of the electroretinograms were significantly reduced in the light-exposed eyes, with the c-waves more reduced than the a- and b-waves. The bicarbonate response was also significantly reduced in the irradiated eyes. CONCLUSIONS: The decrease of the bicarbonate response of the standing potential indicated that significant functional damage of the retinal pigment epithelium was induced by the light exposure.     

The effects of L-and D-ascorbic acid administration on retinal tissue levels and light damage in rats.

To assess the protective effect of ascorbic acid in retinal light damage of rats, we have determined the uptake and retinal tissue distributions of its L- and D- stereoisomers following interperitoneal or intraocular injections. The effects of intense-intermittent light exposure and darkness on tissue ascorbate were compared by measuring its levels in retina and retinal pigment epithelial tissues at various times after administration. The protective effects of the two forms of ascorbate against retinal light damage were also compared by measuring rhodopsin levels 2 weeks after intense light exposure. After interperitoneal injection, both forms of ascorbic acid were higher in the retinal pigment epithelial-choroid-scleral complex (eye cup) than in the retina. Over a 2 hr post-injection period, L-ascorbate in the eye cup was 2 to 4 fold higher than normal (10-11 nmol); D-ascorbate levels were between 15 and 30 nmol. During the same period retinal L-ascorbate was just above normal (12-14 nmol), whereas less than 5 nmol of D-ascorbate was present. When ascorbate was given by the intraocular route the opposite effect was found. During the 2 hr post-injection period retinal L-ascorbate levels were 2 to 5 fold higher than normal; D-ascorbate was between 25 and 50 nmol/retina. Within 1 hr post-injection, L-ascorbate in the eye cup was near normal and D-ascorbate levels were 10 nmol or less. In uninjected rats perfused with normal saline, the endogenous L-ascorbate was distributed 55% in the retina with 9% and 36%, respectively, in the RPE-choroid and sclera. Ten-thirty min after interperitoneal peritoneal injection about 40% of the L-ascorbate was present in the retina with 17% and 44% in the RPE-choroid and sclera. Total ascorbate (L + D) levels in the same tissues of D- injected rats were similar to those found for rats given L-ascorbate. Following 7 hrs of darkness, tissue ascorbate levels in the injected rats decreased to approximately the same levels present in uninjected animals. For rats exposed to intense light average retinal ascorbate levels decreased further, while RPE-choroid and scleral levels were largely unchanged from the dark control levels. About 50% of the tissue ascorbate was present in the retina 10-30 min after intraocular injection. The RPE-choroid contained between 10 and 14% of the ascorbate, with 35-40% present in the sclera. Retinal ascorbate levels remained high in the injected eyes following 2.5 hrs of darkness, but decreased as a result of intense light treatment.(ABSTRACT TRUNCATED AT 400 WORDS)