Fetal Alcohol Syndrome: An Ophthalmologic Perspective
Fetal Alcohol Syndrome (FAS) is an irreversible congenital condition that is a result of maternal alcohol use during pregnancy. Classic signs include: abnormal facial features (short palpebral fissure, thin vermillion border, and smooth philtrum), growth retardation, and neurobehavioral impairment. These signs range greatly in severity, and can include any mix of the classic signs. FAS is a syndrome that falls under a larger group of conditions known as Fetal Alcohol Spectrum Disorder (FASD). FASD includes Alcohol-Related Neurodevelopmental Disorder (ARND), Alcohol-Related Birth Defects (ARBD), partial-Fetal Alcohol Syndrome (pFAS), and FAS, which is considered the most severe syndrome.
Alcohol is a known CNS teratogen that causes reduced brain volume and irregular brain and facial structure. Though there are many hypotheses, the exact mechanism by which alcohol induces CNS and structural changes is still unclear3. Some proposed mechanisms include: direct cytotoxic effect to embryonic cells (specifically the anterior neural ridge which organizes the prosencephalon), epigenetic changes leading to disrupted neural plasticity, and disruption of retinoic acid-based cell signaling.
One CDC study showed FAS occurring in 0.3 out of 1000 children from 7-9 years old. More recent studies have shown FAS to have a prevalence as high as 98.5 per 1,000 in certain US populations8-10.
Ocular Specific Pathology
- Short horizontal palpebral fissures (decreased distance between the medial eye canthi and lateral eye canthi) commonly found and easy to measure.
- Telecanthus (increased distance between the medial eye canthi) is commonly found in FAS.
- Epicanthus (vertical fold of skin on the lateral nose), with one study finding up to 80% of infants exposed to alcohol having epicanthus.
- Microphthalmia (abnormally small eyes) is commonly found in FAS and can aid in diagnosis of FAS.
- Strabismus (abnormal alignment of eyes) is non-specific, but commonly found in FAS.
- Blepharoptosis (drooping of upper eyelid) is non-specific, but can be seen in some FAS patients.
- Small optic discs
- Decreased vision
- Decreased number of optic nerve axons
Increased tortuosity of the retinal vessels was found in up to 49% of Swedish children with FAS. Fundus abnormalities including optic nerve hypoplasia and tortuosity of the retinal vessels seems to remain unchanged throughout childhood and adolescence.
Decreased visual acuity
- Attributed to optic nerve hypoplasia and increased tortuosity of retinal vessels.
- In one study, up to 65% of FAS children had decreased visual acuity.
- More than half of FAS children with visual impairment had severe acuity < 0.2.
Eye movement (motor control and executive function)
- Children with FASD had elongated reaction times, excessive direction errors, and no express saccades.
- Possible dysfunction of frontal lobes
- Eye movement tasks could be another possible tool for assessing FAS in children as well as measuring executive function in FAS patients.
There is no known safe limit of alcohol consumption during pregnancy. Both quantity and pattern (binge) of drinking are more likely important factors in the teratogenic effects. Pregnant women and reproductive- aged women without reliable contraception should be advised to abstain from alcohol.
Detection through ophthalmologic exam
FAS often get missed in newborns and neonates, and is sometimes diagnosed as late as early adulthood. Early detection and diagnosis leads to significantly less comorbidities and symptoms in later life of FAS patients. With rising prevalence of FAS, there is an opportunity for ophthalmology to drastically reduce the morbidity of FAS patients through a thorough eye exam. Some studies suggest a full ophthalmic exam in all children who are suspected of having FAS. This includes: inspection of periocular features (supplemented with morphometric analysis if needed), visual acuity (with visual evoked potentials), slit lamp exam, and ophthalmoscopic exam (particularly the optic disc looking for optic disc hypoplasia and tortuosity of retinal vessels). In addition, ocular abnormalities seem to remain unchanged and persistent throughout childhood and adolescence, increasing the odds of diagnosing FAS. Providing an FAS diagnosis earlier through eye exam could help provide earlier management of problems and reduce both ocular comorbidities (vision loss) and cognitive/neurobehavioral comorbidities.
FAS is diagnosed clinically and requires at least 2 of these findings: characteristic facial features (short palpebral fissure, thin vermillion border, smooth philtrum), signs of growth retardation (height and/or weight <10th percentile), clear evidence of brain involvement, or neurobehavioral involvement. Documented maternal alcohol use is not needed for diagnosis, but can help provide evidence for FAS if positive.
Ocular Signs and Symptoms
The only ophthalmologic diagnostic criteria for FAS is short palpebral fissures. But, as discussed earlier, there are many periocular and intraocular signs that can point to a diagnosis of FAS. Ocular signs present earlier than signs of growth retardation, brain involvement, and neurobehavioral involvement and thus can be more useful in aiding the early diagnosis of FAS. Periocular signs include: short palpebral fissures, telecanthus, epicanthus, microphthalmia, strabismus, and blepharoptosis . Intraocular signs include: optic nerve hypoplasia and tortuosity of retinal vessels. Visual acuity can also be used to aid in diagnosis as FAS children tend to have reduced visual acuity. Eye movement tasks could be another possible tool for assessing FAS in children as well as measuring executive function in FAS patients.
One recent meta-analysis showed that the 5 most prevalent comorbidities of FAS were expressive language disorder, chronic otitis media, conduct disorder, receptive language disorder, and abnormal function of peripheral nervous system and special senses. There also tends to be higher rates of mental disorders in people with FAS.
Syndromes that may appear similar to FAS include: Williams Syndrome, DiGeorge Syndrome, Velocardiofacial Syndrome, Noonan Syndrome, Fetal Hydantoin Syndrome, Fetal Valproate, and Maternal PKU.
Early detection and appropriate behavioral and special education are the most important factors for positive outcomes in children with FAS. These therapies improve social and cognitive abilities and have an inverse relationship with time of diagnosis. Treatment is highly individualized and can include occupational therapists, speech therapists, and cognitive behavioral therapy for patients who suffer from anxiety and/or depression.
There are no specific medications approved to treat FAS, but appropriate medication can be used for related symptoms (e.g. stimulants for hyperactivity).
FAS is an irreversible congenital disorder that can only be prevented by decreasing alcohol quantity during the whole pregnancy. It is a lifelong disorder, and most treatment is symptomatic. Patients generally tend to have lower academic performance, difficulty reading social cues, and higher rates of incarceration.
Prognosis for FAS patients is poor with higher rates of alcohol/drug abuse, psychiatric disorders, unemployment, sexual misconduct, and disability. One study also reported much lower average life expectancy for FAS patients at 34 years old with deaths reported due to suicide (15%), accidents (14%), poisoning by illegal drugs or alcohol (7%), diseases of the nervous and respiratory systems (8% each), and diseases of the digestive system (7%).
Fetal alcohol spectrum disorders 
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