We determined the prevalence of visual and ocular abnormalities in an unselected cohort of Chilean children exposed to large quantities of alcohol in utero compared with matched controls. Major ocular anomalies and vision problems were no more common in our heavily exposed children than in unexposed controls. It is reassuring that the majority of exposed children had no more visual problems than control children, given the high prevalence of ocular abnormalities previously reported among children diagnosed with FAS(2
Although many studies have reported a high rate of major eye malformations in children with FAS, little is known about children who are exposed to high levels of alcohol but do not develop FAS, despite the fact that most heavily exposed children do not develop FAS. There are only two previous studies of the visual system in alcohol-exposed children that included those children who did not have FAS. The first report of ocular abnormalities in alcohol-exposed children who did not have FAS includes only 10 children who did not meet criteria of FAS and of those children; 4 had eye abnormalities (maculopathy, tortuosity, esotropia, and nystagmus)(28
). These children, however, are siblings of those with FAS and may have been referred for evaluation because of eye problems.
In the second study assessing alcohol exposed children, Carter et al prospectively studied effects of prenatal alcohol exposure on visual acuity in 131 South African infants at 6.5 months of age. This study, however, only assessed vision using Teller Acuity Cards and did not examine the ocular structures. This group demonstrated that prenatal alcohol exposure was linked with diminished visual acuity in infancy (27.3% versus 9.3% of the controls, P < 0.005)(3
). This study was limited by lack of complete eye examination; therefore, they were unable to determine the cause (refractive errors, retinal changes, or central nervous system abnormalities) of lower visual acuity scores in infants exposed prenatally to alcohol. The authors also made the important point that acuity deficits seen at 6.5 months may reflect only a maturational deficit or delay in visual system development. They emphasized that their findings required re-evaluation by complete visual assessment later in childhood.
Most of what is known regarding ocular findings in children with complete FAS was described by Stromland et al. Her work has focused primarily on comprehensive examinations performed on children who were diagnosed with FAS(13
). She reported that the majority of children with FAS have ocular findings including optic disc hypoplasia (48%) or retinal vessel tortuosity (49%)(13
). These rates could be elevated by the fact that children may have been referred for visual problems. Moreover, the examiners were not masked to diagnosis.
Other data suggest that rates of ocular malformations are not as high as reported from Sweden. A recent study from Portugal of 32 children with FAS and 25 controls reported retinal vessel tortuosity in 30% and optic nerve hypoplasia in 25% of children with FAS, lower rates than demonstrated previously in Sweden(11
). This group also noted that their patients had better visual acuity (82.7% with normal acuity vs. 35% in the Swedish study), and that the malformations were notably less severe than those seen in Sweden(13
). The authors suggest that referral/selection bias, patterns of drinking, and genetic factors may play a significant role in these differences in rates and severity of abnormalities.
Our data suggest that the high rate of anomalies found by Stromland and others could be due, at least in part, to the way subjects were selected and that Carter’s results may have been due to maturational delay. A possible explanation for the low incidence of ocular abnormalities in our study is that exposure was based on maternal use of alcohol prenatally, not FAS. It is likely that only those subjects with FAS have high rates of ocular abnormalities. The mothers of the exposed population were young (mean age 23.02 years) and the majority of our women were primiparous (63%) potentially attenuating the damaging effects of alcohol, as increasing maternal age and parity are directly correlated with severity of defects caused by prenatal alcohol exposure in both animal and human studies (30
). It is also possible that some of the mothers decreased their consumption of alcohol as a result of being enrolled in this study, and that defects involving growth and development of ocular structures (such as growth of the optic nerve and retinal vessels) may have been averted by this decrease in alcohol consumption. Most mothers in our cohort, however, did not significantly reduce their drinking after study enrollment. Genetic or nutritional differences between the populations studied might also affect the risk of damage to the developing visual system secondary to exposure to alcohol(34
This prospective study examined the ocular structures and visual function comprehensively in unselected children exposed to alcohol and unexposed controls. Eye examinations were performed on all exposed subjects, not just those who had phenotypic changes related to alcohol damage. The ophthalmologist was masked to the exposure status of the children. Our study had some limitations as well. It was designed to examine the effects of heavy exposure to alcohol prenatally; our small number of children does not enable us to comment on the frequency of eye malformations among children with FAS. The reference population used for palpebral fissures was not standardized for the Chilean population and there are no published data regarding ethnic differences in palpebral fissure lengths in the Chilean population. Therefore, we can not rule out that ethnic differences are the reason for the high rates of short palpebral fissure. The relatively high prevalence of short palpebral fissure lengths and epicanthal folds in both the exposed and the control groups may represent a normal variant in this population. Although the precise reason for the high rate of these findings remains unclear, we postulate that the young age of the subjects in combination with the ethnic differences in the Chilean population is the most likely reason for the increase in these findings. Palpebral fissures are known to vary in size according to ethnicity and age(37
). Because of the young age and developmental status of subjects, lack of cooperation could have produced some measurement error. We were also limited by our inability to get many of the subjects to return for eye examinations due to difficulties contacting them.
The high frequency of reported ocular and visual findings among children with FAS has led some to advocate ophthalmologic exams as a diagnostic tool for FASD. Our data indicate that ophthalmologic examinations are not likely to help diagnose FASD, but they may be important in the assessment/evaluation of a child who has FAS.
In summary, this study demonstrates that the teratogenic effect of alcohol on the developing visual system is likely to be limited to children who have FAS, rather than those exposed to high levels of alcohol prenatally who do not develop FAS. These results have several potentially important clinical implications. First, eye examinations are unlikely to help clarify the diagnosis in children suspected of having alcohol related damage. Second, children who do not have classic FAS are not at high risk for eye abnormalities.