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1.  What can we learn from the thalidomide experience: an ophthalmologic perspective 
Current opinion in ophthalmology  2011;22(5):10.1097/ICU.0b013e3283499f24.
Purpose of review
The thalidomide tragedy of the early 1960s resulted in a great number of studies and reports involving many specialties of medicine. Because of the estimated large number of affected children (5000+) worldwide exposed to this potent teratogen, and the many informative cases in which the exposure time was known, a teratogenic timetable was constructed relating affected structures to the time of exposure. This demonstrated that thalidomide had a teratogenic effect between approximately 20 to 36 days after fertilization.
Recent findings
We found that Duane syndrome and its variants were prominent in individuals who were exposed to thalidomide early in the sensitive period (days 20 to 26±). Other anomalies associated with this early effect were aberrant tearing, facial nerve palsy, ear malformations, and autism. Structural eye malformations were less frequent in this early phase, appearing slightly later in the sensitive period.
Summary
This study summarizes the ophthalmologic findings from a number of studies and compares them with respect to the implications of time of exposure. Because the timing of anomalies such as external ear and limb malformations are well established in the thalidomide literature, correlation with associated eye anomalies gives insight into the approximate timing of the causative teratogen exposure.
doi:10.1097/ICU.0b013e3283499f24
PMCID: PMC3713624  PMID: 21825994
aberrant tearing; Duane syndrome; facial nerve palsy; thalidomide embryopathy
2.  Macular Thinning Associated With Unilateral Optic Nerve Hypoplasia 
The authors present the case of an 8-year-old boy with a long-term diagnosis of unilateral optic nerve hypoplasia (ONH) of unknown cause in the right eye. Spectral- domain optical coherence tomography (SD-OCT) of the central macula was consistent with hypoplasia greatest in the inner retinal layers, but also involving the outer retinal layers when compared with the unaffected contralateral eye. Although ONH is commonly associated with hypoplasia of the nerve fiber and ganglion cell layers, it can also be associated with hypoplasia of other layers in the inner and outer retina, including the outer nuclear and photoreceptor inner/outer segment layers, as evidenced by SD-OCT.
doi:10.3928/15428877-20110125-08
PMCID: PMC3690277  PMID: 21323261
3.  Virus-Derived Gene Expression and RNA Interference Vector for Grapevine 
Journal of Virology  2012;86(11):6002-6009.
The improvement of the agricultural and wine-making qualities of the grapevine (Vitis vinifera) is hampered by adherence to traditional varieties, the recalcitrance of this plant to genetic modifications, and public resistance to genetically modified organism (GMO) technologies. To address these challenges, we developed an RNA virus-based vector for the introduction of desired traits into grapevine without heritable modifications to the genome. This vector expresses recombinant proteins in the phloem tissue that is involved in sugar transport throughout the plant, from leaves to roots to berries. Furthermore, the vector provides a powerful RNA interference (RNAi) capability of regulating the expression of endogenous genes via virus-induced gene-silencing (VIGS) technology. Additional advantages of this vector include superb genetic capacity and stability, as well as the swiftness of technology implementation. The most significant applications of the viral vector include functional genomics of the grapevine and disease control via RNAi-enabled vaccination against pathogens or invertebrate pests.
doi:10.1128/JVI.00436-12
PMCID: PMC3372183  PMID: 22438553
4.  Congenital Aberrant Tearing: A Re-Look 
Purpose
Congenital aberrant tearing is characterized by tearing when eating (“crocodile tears”), lack of emotional tearing, or both. Most reported cases are associated with Duane syndrome. In our previous studies we observed aberrant tearing in individuals with thalidomide embryopathy and Möbius sequence. This report summarizes the literature on the subject and adds 3 new studies that give information on this unusual condition.
Methods
Twenty-eight individuals with Möbius sequence were interviewed about tearing symptoms at a support group meeting in Italy. In Sweden 30 adults primarily from the original thalidomide series were reexamined. In this latter study, a Schirmer test was done at baseline and repeated 5 minutes after eating. Twenty families in Brazil who have children with Möbius sequence were questioned about tearing symptoms and exposure to misoprostol during pregnancy.
Results
In the 28 Italian individuals, either “crocodile tears” or lack of emotional tearing was noted in 7 cases. In the thalidomide study, 10 of 30 patients had tearing when eating and 7 had no emotional tearing. Low Schirmer scores or increased tearing after eating was noted in a few asymptomatic individuals. Among the 20 Brazilian children with Möbius sequence, 10 had some tearing abnormality.
Conclusion
Congenital anomalous lacrimation is rare but usually associated with Duane syndrome or abduction deficits, as in Möbius sequence and, less frequently, facial nerve palsy. Studies implicate an early insult in development at 4 to 6 weeks. At that time the facial nerve, sixth nerve, and lacrimal nucleus are in close proximity in the embryo.
PMCID: PMC2646435  PMID: 19277226
5.  AUTISM WITH OPHTHALMOLOGIC MALFORMATIONS: THE PLOT THICKENS 
ABSTRACT
Purpose
To review the association of autism spectrum disorder (ASD) in individuals manifesting thalidomide embryopathy and Möbius sequence and compare them with three new studies in which ASD was also associated with ocular and systemic malformations: (1) a Swedish study of individuals with CHARGE association (Coloboma, Heart, choanal Atresia, developmental or growth Retardation, Genital anomaly, and Ear involvement); (2) a Swedish study of Goldenhar syndrome; and (3) Brazilian Möbius syndrome (sequence) study.
Methods
In the Swedish CHARGE study, 31 patients met the inclusion criteria (3+ or 4 of the common characteristics of the CHARGE syndrome). The same team of investigators also evaluated 20 Swedish patients with Goldenhar syndrome. In the Brazilian Möbius study, 28 children with a diagnosis of Möbius sequence were studied; some children had a history of exposure during their mother’s pregnancy to the abortifacient drug misoprostol in an unsuccessful abortion attempt
Results
In the CHARGE study, five patients had the more severe autism disorder and five had autistic-like condition. In the Goldenhar study, two had autism disorder and one had autistic-like condition. In the Brazilian Möbius study, the systemic findings of the misoprostol-exposed and misoprostol-unexposed patients were almost undistinguishable, and ASD was present in both groups (autism disorder in five and autistic-like condition in three).
Conclusion
Autism spectrum disorder has been reported in two conditions with known early pregnancy exposure to the teratogenic agents thalidomide and misoprostol. In the Brazilian Möbius study, autism also occurred in both the misoprostol-exposed and misoprostol-unexposed groups. Autism also was present in patients with both CHARGE association and Goldenhar syndrome.
PMCID: PMC1280092  PMID: 15747750

Results 1-5 (5)