The Goldmann perimetry revealed an absolute central scotoma. Traces of thallium were found in the urine and in the serum. The district attorney later discovered ...
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International Ophthalmology 21: 143–147, 1997. c 1997 Kluwer Academic Publishers. Printed in the Netherlands.
A case of localized retinal damage in thallium poisoning Dieter Schmidt, Michael Bach & J¨urgen Gerling Universit¨ats-Augenklinik, Freiburg, Germany Accepted 28 October 1997
Key words: thallium poisoning, optic atrophy, bipolar cells, multifocal ERG
Abstract Purpose: To determine the cause of visual impairment and to document the late eye disturbances in a case of thallium poisoning. Patient: A 44-year-old woman presented with a history of repeated attacks of complete alopecia over a period of several months, diffuse pain in both legs, transient gastrointestinal disturbances, abasia with a progressive paraparesis, paresthesia in the fingertips, and polyneuropathy. She complained of slowly progressive visual deterioration in both eyes which began about six months after the first attack of alopecia. The optic discs showed distinct signs of temporal atrophy together with a deep temporal excavation. The Goldmann perimetry revealed an absolute central scotoma. Traces of thallium were found in the urine and in the serum. The district attorney later discovered that her husband had been trying to poison her with thallium. Methods: The clinical and electrophysiological examinations included visual evoked potentials (VEP) and electroretinography (flash ERG, multifocal ERG and pattern ERG). Results: The VEP showed a reduction in amplitude and a prolonged latency indicating a conduction block. The pattern ERG was initially normal. At a follow-up examination 6 years later, a slight amplitude reduction in the pattern ERG was found. The multifocal ERG showed a diminished amplitude in the center of the retina (up to 10 visual angle). Conclusions: The electrophysiological investigations in our patient – who had an optic atrophy – indicated a conduction block of the retinal nerve fibers (VEP) and an additional lesion at or before the retinal bipolar cells (multifocal ERG), localized in the central 10 . These findings suggest that thallium poisoning can lead to a combined lesion of the retinal nerve fibers and the neural retina. Introduction The ophthalmological signs associated with thallium poisoning fall into two categories: early and late. The early signs include conjunctivitis, blepharitis, diplopia, ptosis, bilateral facial paresis, hyperesthesia and hypesthesia in the head region, nystagmus, hyperemia of the optic disc, and optic neuritis [1–9]. If the condition is not fatal, many of the early signs may be transient. The late signs are optic atrophy together with a central scotoma that occurs several months after intake of the poison [8, 12–22]. Optic atrophy with a distinct decrease in visual acuity can occur within 7 weeks of poison intake [10]. The visual disturbance can develop rapidly [1, 11]. Kaps [1] described the case of a young patient in whom complete blindness occurred within a few days. Recovery after optic nerve involvement has
also been described [18]. The severity of the visual impairment depends on the dosage [8, 20]. We describe a patient with a history of repeated thallium poisoning over a period of many months. We used electrophysiological methods to determine the sites of the lesion in the visual pathway.
Methods The patient underwent clinical examinations in 1989, 1990 and 1996. The visual fields were assessed using the Goldmann perimeter. In order to obtain information on the site of the lesion caused by thallium intoxication, the scotopic and photopic ERG, the pattern-ERG, and the visual evoked potentials (VEP) were performed initially and repeated 6 years later. Additionally, a multifocal ERG (VERIS-system by EDI, San Francisco;
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Figure 1. Temporal atrophy of the optic discs, August 1989.
Figure 2. Nerve fiber layer photograph: massive defects of the retinal fibers.
Sutter and Tran [23]) was performed in 1996. ERG responses were recorded with DTL electrodes placed near the lower limbus, using an ipsilateral gold cup electrode as reference. A visual field of 33 was covered with 61 stimulus elements. The monitor had a frame rate of 75 Hz and a luminance of 70 cd/m2 . The first-order response from the photopic multifocal ERG is assumed to represent the bipolar cell and/or photoreceptor activity [24].
paresis, paresthesia in the fingertips, and for the first time, visual impairment developed. She also had her third attack of complete alopecia in July. During these months, she experienced insomnia and mental aberration. At the end of July 1989 the patient developed a severe paraparesis, more pronounced distally, with decreased tendon reflexes in the lower extremities; in addition, she was ataxic on standing and walking and had a distally pronounced pallhypesthesia without sensory loss. She was treated with neuroleptic drugs. Mees’ stripes had developed in her fingernails. Electromyographically a severe axonal polyneuropathy could be demonstrated, with signs of denervation in the leg muscles and in the muscles of her hand. These signs suggested intoxication by a heavy metal. Traces of thallium were found by polarography on three measurements in the urine and once in the serum but not in the CSF. After discontinuing the neuroleptic drugs, walking improved and the pareses disappeared. The perception disorder also receded. Only the hypesthesia of the calf remained for several months. The district attorney later discovered that her husband had been trying to poison her with thallium.
Results General findings The 44-year-old woman complained of impairment of the sense of taste and eczematoid changes of the skin flexures of several joints and of the pubic region. In January 1989 she had a nervous breakdown during a marital conflict. She developed a complete alopecia which included the eyebrows and the pubic hair. The hair loss was first attributed to her mental condition. At the beginning of April 1989 she experienced diffuse pain in both legs, without any difficulty in walking, which disappeared spontaneously after 2 to 3 weeks. Once more she lost all her hair, which in the meantime had grown again. In June she experienced transient gastrointestinal disturbances with nausea, vomiting and constipation. In July she complained of pain and dysesthesia in her legs. Abasia, progressive para-
Ophthalmological examination In August 1989, the patient complained of a slowly progressive deterioration in the vision of both eyes
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Figure 3. Visual fields, Goldmann perimetry, August 1989.
Figure 4. Central depression in the multifocal ERG (1996). Raw local ERGs are at the top, and 3-D-plots at the bottom. Each response trace corresponds to one hexagonic area.
during the previous 8 weeks. The visual acuity of both eyes was initially 20/300, two weeks later 20/400 and remained at this level thereafter. There was no relative afferent pupillary defect and no anisocoria. The motility of the eyes was normal. The anterior segment and the fundus were normal, the optic disc was normal in color, with a blurred nasal margin, more pronounced in the right eye. Two weeks later the optic discs began
to show signs of atrophy. After 3 months and after one year, both optic discs showed distinct temporal atrophy (Figure 1) with a deep temporal excavation and a decrease in the number of nerve fibers in the papillomacular bundle (Figure 2). In August 1989 and again in December 1990, the Goldmann visual fields of both eyes showed an absolute central scotoma (III/4), about
146 25 in diameter, extending further into the upper than into the lower field (Figure 3). Electrophysiological examination in August 1989: The a- and b-waves in the scotopic ERG showed a normal amplitude and a normal latency. The photopic ERG was also normal. The pattern-ERG, recorded at the same time, was also normal in both eyes. The visual evoked potentials (VEP) showed a considerable reduction in amplitudes and a prolonged latency for both eyes. In December 1990 the VEP recordings did not show any measurable amplitudes corresponding to the definite atrophy of the papillomacular nerve fiber bundle. In October 1996 the electrophysiological examination was as follows: The photopic and scotopic ERGs, recorded from both eyes were normal. The pattern ERG showed a slightly reduced amplitude in both eyes. The VEP was unchanged compared to 1989; there were still no measurable amplitudes to VEP stimuli. The multifocal ERG (Figure 4) showed that the expected response peak in the center is missing while the midperipheral responses are in the normal range. The normal peripheral values explain the normal flashERG response. The missing central peak suggests that the function of the photoreceptors and/or bipolar cells is affected within about 10 visual angle. Discussion The electrophysiological examinations in this patient with repeated chronic thallium intoxication revealed changes in the multifocal ERG, the pattern ERG and the VEP. The amplitude reductions in the pattern ERG reflect the damage to the retinal ganglion cells and the visual pathway which is clinically seen as optic nerve atrophy with a deep temporal excavation. Additionally, the multifocal ERG showed a distinct reduction of the amplitudes in the central retina of both eyes reflecting circumscribed damage to the retinal cells. The normal midperipheral values in the multifocal ERG explain why the standard flash-ERG response was normal, as the latter is a mass response from the entire retina. In our patient we found that oral thallium poisoning can lead to optic nerve fiber loss with ganglion cell impairment and also to bipolar cell impairment predominantly in the center of the retina. Since our patient showed impairment of the bipolar cells exclusively in the center of the retina, another mechanism of damage is possible. Reports by Holl¨ander [25] and W¨assle [26]
suggest that atrophy of the retinal ganglion cells could affect amacrine cells and bipolar cells transsynaptically. Thus, the severe amplitude reduction of the central neural retina seven years after oral thallium poisoning may represent transsynaptic degeneration from the affected ganglion cells. Optic nerve impairment as shown by disc atrophy and VEP reduction has been described in cases of severe poisoning. Moore et al. [27] and Vrij et al. [28] found that visual evoked potentials were distinctly delayed in patients with optic atrophy after severe poisoning. Ganglion cell loss of the retina was proved by a histological investigation [29] in a case of thallium intoxication with optic atrophy. Involvement of the neural retina, especially of the bipolar cells, as apparent in the central retina of our patient, has also been discussed before: Hennekes [30] reported on ERG findings in a 34-year-old male suffering from thallium poisoning. The scotopic b-wave was hypernormal and the b-wave amplitude-intensity function was pathologic, suggesting a direct effect of thallium on the neural retina. Potts & Au [31] reported on the biochemical similarity of the thallous ion and the potassium ion and found in animal experiments, high levels of the radioactive isotope Tl204 in the lens, retina, and optic nerve tissue. These electrophysiological and biochemical findings corroborate the assumption that impairment of the neural retina as well as lesions of the retinal nerve fibers occurred together in our patient. Photoreceptor impairment was discussed by Shamshinova et al. [32] who reported a loss of photoreceptors particularly in the peripheral area of the retina in the rabbit eye. Since this defect was seen after experimental intravitreal administration of thallium, this result could also be a direct toxic effect of the highly concentrated intravitreal agent. Our findings of a reduced multifocal ERG in the center of the retina suggest that thallium poisoning can lead to a combined lesion of the retinal nerve fibers and the central neural retina.
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Address for correspondence: D. Schmidt, Department of Ophthalmology, Univ.-Augenklinik, Killianstr. 5, D-79106 Freiburg, Germany
