This study focused especially on retinal and visual function examinations because of the possibility of evaluating patients using new OCT and ERG techniques.
Mercury vapor is a significant source of mercuric load in occupational exposure because it is odorless and colorless and tends to accumulate in poorly ventilated areas. Once the lungs have absorbed the inhaled vapor, the mercury can reach different tissues via the bloodstream, with the primary target the CNS and eyes because of proximity [2, 23]. When it is oxidized, it cannot penetrate the blood-barrier again and remains for prolonged periods in tissues [2, 7, 8, 23].
As mentioned, the neurologic and thus the visual pathway effects resulting from mercury toxicity have been described widely [2, 23, 24].The long-term exposure effects can include symptoms from tremor, neuropathy, personality changes referred to as mercurial erethism, speech disruption, delirium or rigidity to symptoms of VF defects, reduced VA, color and night vision, or decreased CS [2, 23, 25, 26]. However, the introduction of electrophysiology testing has established the presence of primary retinal involvement and that not all alterations of the visual pathway are due to CNS poisoning [6].
As mentioned, the first patient complaints were attributed to a viral infection, which delayed the diagnosis. Thus, when diagnosed correctly, the mercuric values in urine (mean, 302.86 µg/g Cr) and blood (mean, 392.93 µg/L) significantly exceeded the maximal accepted level for occupational exposure (< 30 µg/g Cr and 10 µg/L, respectively) [9, 10]. In such cases, the mainstay of treatment is chelation therapy; however, only three patients underwent early chelation, which was stopped prematurely because of severe adverse reactions. Fifteen workers underwent delayed chelation (8 to 12 months after the initial incident). However, late chelation did not result in significant symptom relief.
Twenty-six workers exhibited symptoms related to erethism. Some also showed typical symptoms associated with cognitive mercury poisoning such as memory and attention disturbances [23, 24]. Tremor of the hands, head, and eyelids, a late symptom of mercury poisoning, also occurred in some patients. EMG showed signs of mixed sensorimotor polyneuropathy and multiple mono-neuropathy alterations 12 to 18 months after exposure.
In this series, the VA decreased minimally and occurred in nine patients from G1 and five from G2; however, advanced visual functions were impaired significantly apparently independently of the mercury levels since significant negative correlations were seen only among the BML, BCVA, and ffERG.
Color vision and CS impairment at high spatial frequencies also were found, with the most frequently observed color vision alteration in the blue-yellow range. These findings agreed with previous studies [25, 27–29].
The most prevalent VF pattern was concentric constriction (17 eyes, 29.3%), which agreed with previous studies [30, 31]. This visual impairment may have a central origin (calcarine cortex), as it has been reported previously [32]. In addition, the increased implicit time of P100 in the affected patients, especially in G3, indicates delayed nerve conduction and involvement of the visual pathway. da Costa et al. also reported this finding in 2008 (Costa et al. 2008). In the current series, significant retinal involvement also was seen, since the same patients showed retinal dysfunction in the ffERG, PERG, and mfERG tests, with both a generalized retinal response loss and alteration of the central retinal area, which could have affected the results obtained in the VF tests.
The ffERG showed changes in the SRR and OP of the ISCEV protocol, suggesting that rod cells are impaired by acute mercury-vapor intoxication. We did not find differences in the MSR, 30-Hz flicker, and SFCR data, which are key for assessing macular cone function, in the global sample compared to controls; however, significantly lower measurements were found in the ffERG in G3 compared to the controls, together with a lower amplitude of P50 in the PERG, suggesting that the cone cells and ganglion macular cells can be affected by mercury poisoning. These findings reinforce the idea that both the outer and inner retina visual processes are involved. Finally, the mfERG results are further evidence of damage to the photoreceptor pathway in mercury poisoning, since the amplitudes showed loss of the retinal response within the central 50 degrees, as reported previously [6].
A discrepancy was observed between the dysfunction patterns observed in the VF and the mfERG, with less involvement in the mfERG. This finding suggested retinal damage (detected by the mfERG) in addition to that in the visual pathway.
The latency and amplitude of PRPEV were not correlated with the BML; however, patients in G3 had latencies significantly over 100 milliseconds and significantly reduced P100 amplitudes. Although these results typically occur in optic neuropathies and visual cortex abnormalities, they also can be associated with maculopathies, especially when they are interpreted in conjunction with retinal function tests (PERG, mfERG, and ffERG). These results agree with the results reported by Ventura et al. and da Costa et al. in patients with mercury poisoning [6, 19].
Despite the functional retinal involvement and in contrast to the results obtained by Ekinci et al [7, 8], OCT did not reveal structural changes in the RNFL, macular CRT, and choroid thickness when results were compared to the normalized reference values [17, 18]. These differences might be related to the intensity and the manner of poisoning, as the current patients reached higher levels of mercury in a short time compared to the long exposure times of workers examined by Ekinci et al [7, 8].
This study has some limitations. There were no environmental measurements of mercury either before the accident or during the occupational incident. In addition, probably only the most affected patients were evaluated at the IOBA-Eye Institute, and the time that elapsed after the acute accident and the assessment at the IOBA likely was not the most appropriate for adequate follow-up over time. Most of the identified visual alterations, in our opinion, were attributable to the occupational exposure to mercury vapor, but we do not know the ophthalmologic baseline status before the accident. In addition, because of the lack of programmed follow-up, we had no information about the current clinical situation or about the evolution of most patients. Regarding the electrophysiologic tests, since half of the contaminated patients presented with no VA alterations, the results obtained from the global sample probably are affected by this patient subgroup. For this reason, our attention was focused on the subgroup G3. In addition, caution should be exercised when interpreting the results obtained from the comparisons between the control group and subgroup G3, because the samples size might be small for both groups in some comparisons. Finally, the OCT technology has evolved so rapidly that it is possible that with OCTs based on swept-source or ultra-high resolution it would have been possible to detect changes in the retinal or choroidal structures.
Even so, this study presents some relevant findings from a very rare and extremely serious event, for which references are scarce. First, the VA is affected slightly and there is more VF involvement. However, other visual function assessment tests seem to behave independently of the mercury levels. The most prevalent VF alteration is decreased VFs, but central involvement also was found. This finding could be of retinal and/or neurologic origin considering the mfERG results. No anatomic retinal changes were identified in this series, but it is possible that the new OCT systems allow establishing the structural bases of these alterations. Delayed chelation apparently did not benefit the patients.
In summary, despite its limitations, this series of patients affected by the same event contributes to the information obtained about mercury poisoning for future similar situations.