Efavirenz
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Initial concerns about teratogenicity were based on animal studies and human case reports. In a study of pregnant cynomolgus monkeys treated with efavirenz at a dose that produces plasma drug levels similar to those in humans given efavirenz 600 mg once daily, malformations were observed in 3 of 20 fetuses/infants from efavirenz-treated monkeys compared with none of 20 concomitant controls. The abnormalities observed were anencephaly and unilateral anophthalmia in one fetus, microphthalmia in another fetus, and cleft palate in the third fetus (Bristol-Myers Squibb, 2015). There are five case reports of neural tube defects and one case report of another central nervous system defect (Dandy-Walker syndrome) in infants from pregnant women who took efavirenz during pregnancy, all of whom were exposed in the first trimester. Of the four neural tube defects for which information is available, myelomeningocele was observed in two infants (De Santis et al., 2002; Fundaro et al., 2002; Saitoh et al., 2005), anophthalmia with severe oblique facial clefts and amniotic banding in one infant (Shanske, 2012), and encephalocele in one infant (Gudu and Bekele, 2013).
Radiation Injuries to Human Fetuses
Kedar N. Prasad in Handbook of RADIOBIOLOGY, 2020
Among eye defects, anophthalmia and microphthalmia are common gross responses in rodents exposed to 100–300 Rat a particular stage during fetal life. Although the developing retina is sensitive to radiation, it exhibits a remarkable capacity to reconstitute and repair the damaged area. Even after reconstitution of the retina, there is evidence of persistent damage in the form of microphthalmia. There is a progressive fall in radiosensitivity during the first week after birth as retinal cells become differentiated. A dose of 15 rads to the rat fetus produces brain and eye abnormalities.44 The exposure of the fetus to doses of less than 5 rads may produce eye defects in the F2 generation.45 In another study, the incidence of anophthalmia in live mouse embryos irradiated at 8 days of gestation with neutrons increased and then declined. In contrast, X-ray-induced anophthalmia showed only an increase with dose (Figure 15.5).75 The decline in incidence of anophthalmia in neutron-irradiated embryos was due to increased mortality in utero.
Rubella Virus Infections
Sunit K. Singh, Daniel Růžek in Neuroviral Infections, 2013
The typical cataracts and pigmentary retinopathy seen in CRS were described by Gregg in 1941. The cataracts may consist of a central dense pearly white opacity (Figure 17.5e) or may be total with a more uniform density throughout the lens. Bilateral cataracts are found in about 50% of affected infants; they are usually present at birth but may not be visible until several weeks later. Cataracts, which are often accompanied by microphthalmia (Figure 17.6 a,b), are a useful marker for surveillance of CRS (Bloom et al. 2005; WHO 1999; Vijayalakshmi et al. 2007). Retinopathy is found in about 50% of affected infants. Hyperpigmented and hypopigmented areas of the retina give it a “salt and pepper” appearance, which can be a useful diagnostic indicator of CRS; however, because it does not cause any visual defects, it may not be suspected. Retinopathy is due to a defect in pigmentation and usually involves the macular areas. Glaucoma is less frequently observed than cataract. Other symptoms are pupil rigidity, cloudy cornea, corneal opacity, microcornea, iris hypoplasia, optic atrophy, anophthalmos, chronic uveitis, corneal hydrops, choroidal neovascularization, and keratoconus (Arnold et al. 1994; Vijayalakshmi et al. 2007). Some of these ocular abnormalities may occur later in life (see below).
The Effect of Congenital and Acquired Bilateral Anophthalmia on Brain Structure
Published in Neuro-Ophthalmology, 2021
Holly Bridge, Gaelle S. L. Coullon, Rupal Morjaria, Rebecca Trossman, Catherine E Warnaby, Brian Leatherbarrow, Russell G. Foster, Susan M. Downes
Congenital bilateral anophthalmia is the absence of both eyes and is characterised by a ‘visual’ system that has never experienced pre- or post-natal visual stimulation. Congenital anophthalmia without any other neurological impairment provides an ideal population to study the effects of complete visual deprivation on healthy brain tissue. The same is true of acquired bilateral anophthalmia where both eyes are lost either through trauma or surgical removal of both eyes due to diseases such as retinoblastoma, or end-stage glaucoma, and thus occurs after visual system development. Comparing congenital and acquired bilateral anophthalmia allows the study of visual pathway and whole-brain reorganisation and/or degeneration in the context of complete vision loss taking place either before (congenital) or after (acquired) visual system development.
Characteristics and management of congenital anophthalmos and microphthalmos at a tertiary eye hospital
Published in Orbit, 2019
Alicia Galindo-Ferreiro, Sahar M Elkhamary, Fatimah Alhammad, Laila AlGhafri, Manar AlWehaib, Dalal Alessa, Saif Aldossari, Patricia Akaishi, Rajiv Khadekar, Osama AlShaikh, Silvana Artioli Schellini
Anophthalmia and microphthalmia are rare conditions that can be challenging to manage. Anophthalmia is a complete absence of the eye due to deficient formation of the optic vesicle during early gestation. Microphthalmia indicates a small eye within the orbit due to poor development or regression of the optic vesicle.1 Clinical true anophthalmia is the complete absence of ocular structures in the orbit.2 Microphthalmia indicates the presence of a hypoplastic or rudimentary eye at birth3 with corneal diameter less than 11 mm, or axial length less than 21 mm.4,5 Severe microphthalmia can be difficult to distinguish from clinical anophthalmia in routine ophthalmic practice.1 The deficient orbital volume leads to progressive palpebral and facial developmental anomalies, which are more pronounced in cases of true congenital bilateral anophthalmia or anophthalmia associated with syndromes.6
SIX6-related anophthalmia/microphthalmia: second report on a deletion in a consanguineous family
Published in Ophthalmic Genetics, 2021
Asha Deepthi, Omar Fakhoury, Mohamad Daher, Alicia Gambarini, Stephany El-Hayek, André Megarbane
The proband (Figure 1a) is a male child. Noted by his parents, the proband had normal growth parameters at birth apart from atypically closed eyelids. At 3 months of age, the patient was observed with delayed developmental milestones. By the time the patient was 15 months old, he could walk, but only with assistance. Language was absent and his growth parameters were at the 50th centile. He was seen at our clinic at age 11.5. He presented with severe psychomotor delay and intellectual disability (ID). His OFC was 51 cm (50th percentile); his height 123 cm (5th percentile); and his weight was 21 Kg (5th percentile). Upon examination, he was found to have enophthalmos and thin skin (Figure 1a). There was no history of seizures. Ophthalmological examination revealed bilateral anophthalmia, with no vestigial tissues or any eye remnants. No eyelid abnormalities were seen either. Brainstem auditory evoked response and brain MRI were normal (Table 1).
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