Sue Crowe

SOX2 mutation causes anophthalmia, hearing loss, and brain anomalies

The SOX2 transcription factor is expressed early in the embryonic stem cells of the blastocyst and later in the neural stem cells. It is a member of the SOX family of proteins that carry a DNA‐binding high‐mobility group domain and additional domains that regulate embryonic development and cell fate determinations. We surveyed 93 patients with severe eye malformations for mutations in SOX2. Here, we report a novel nonsense mutation in one female patient with bilateral clinical anophthalmia, absence of all optic pathways, and other neurological abnormalities. The mutation, Q155X, creates a premature termination codon early in the transcriptional activation domain and is likely to be a null allele. Our data show that mutations in SOX2 can cause not only anophthalmia, but also aplasia of the optic nerve, chiasm and optic tract, as well as modest bilateral sensorineural hearing loss, and global developmental delay, underscoring the importance of SOX2 in early human eye and brain development.

The Value of Keratometry and Central Corneal Thickness Measurements in the Clinical Diagnosis of Marfan Syndrome

PURPOSE To explore the utility of keratometry and central corneal thickness (CCT) measurements in diagnosis of Marfan syndrome. DESIGN Retrospective chart review of 211 patients referred for ocular examination to rule out Marfan syndrome. METHODS Patients were categorized into Marfan or control groups using current clinical diagnostic criteria. Patients in whom Marfan syndrome could be neither diagnosed nor ruled out were categorized as inconclusive. Those with other connective tissue diseases were excluded from the study. T tests were performed on keratometry and CCT values, and odds ratios (ORs) were calculated. RESULTS Sixty-two patients were in the Marfan group and 98 patients were in the control group. Mean age of the Marfan group was 22.3 years vs 19.3 years in the control group (P = .23). Marfan patients had significantly lower keratometry and CCT values than controls (40.8 diopters (D) [Marfan] vs 43.3 D [control], P = 4.0 x 10(-19); and 543.5 microm [Marfan] vs 564.2 microm [control], P = 9.1 x 10(-6)). The maximum OR for keratometry (17.6) was calculated at 42 D. In Marfan syndrome patients without ectopia lentis, these values were 41.5 D (P = .00026 vs control) and 542.0 microm (P = .0011 vs control). CONCLUSION There was a highly significant difference in keratometry values between Marfan and control patients, and values less than 42 D could be used as a clinical diagnostic criterion for Marfan syndrome. Significant overlap in CCT values between Marfan and control patients suggests that further investigation is necessary to determine the clinical utility of CCT measurements.

Relationship between the axis and degree of high astigmatism and obliquity of palpebral fissure

PURPOSE To investigate a possible relationship between the slanting of palpebral fissures and the magnitude and axis of astigmatism in children with astigmatism. METHODS Cross-sectional study at a referral center of 53 children with astigmatism of more than +1.50 D in at least 1 eye. Visual acuity testing, cycloplegic refraction, slit-lamp biomicroscopy, and ophthalmoscopy were done on every patient. Corneal topography was obtained in 40 cooperative patients. External photographs of the midface were taken in 45 children. The degree of slanting of the palpebral fissures was evaluated based on the photographs. The statistical analysis tool used was repeated measures analysis of variance. Patients in whom photographic analysis was not available were excluded from the part of the statistical analysis dealing with eyelid slant. RESULTS Palpebral fissure slant (P =.013) and gender (P =.0005) were highly correlated with the obliquity of cylinder axis. There was a possible correlation between gender and eyelid slant (P =.0594), with females having slightly larger degrees of upward palpebral fissure slanting and male more downward slanting of their fissures compared to published angles in an age-matched population. We found a statistically significant correlation between the degree of total astigmatism and a larger abnormal slant (P =.0192) and between the axis and magnitude of corneal astigmatism and abnormal slant (P =.0092). Higher degrees of eyelid slant (> 8 degrees or < -4 degrees ) increased the risk of high cylinder magnitude (> 3.00 D) by an odds ratio of 4.17 (95% CI: 1.03, 19.95). CONCLUSIONS Children with astigmatism with large degrees of slanting of their palpebral fissures are at higher risk for high astigmatism (> 3.00 D). The axis of the astigmatism is highly correlated with the slanting of the palpebral fissure.

Sequencing Analysis of the ATOH7 Gene in Individuals with Optic Nerve Hypoplasia

Abstract Background: The Atonal Homolog 7 (ATOH7) gene has been implicated in association studies with optic nerve head diameter size. Hence, we screened optic nerve hypoplasia (ONH) patient DNA samples from Australia, France, and the United States for sequence variants in theATOH7 gene using Sanger sequencing. Methods: Sanger sequencing of theATOH7 gene was performed on 34 affected individual DNA samples. Sequencing was also carried out in three unaffected family members to confirm segregation of identified single nucleotide variations. Results: Seven sequence variations were identified in ATOH7. No disease-causing sequence changes in the ATOH7 gene was discovered in the ONH patient samples. Conclusions: Mutations within the ATOH7 gene are not implicated in the pathogenesis of optic nerve hypoplasia in our patient cohort.

Observations on the Development and Progression of Unilateral High Myopia

Purpose The purpose of this article is to document the rare observation of the development, progression, retinal changes, and results of visual rehabilitation in a young child with unilateral high myopia, as well as additional clinical observations in four very young patients with this condition. We also examine the role of factors such as amount of astigmatism, presence of strabismus, degree of anisometropia, and penalization in the development of optimal vision in these patients. Materials A review of patients from 1997–2002 disclosed 33 individuals with a diagnosis of unilateral high myopia. Five children with adequate information on the progression of myopia and/or in whom a final visual outcome could be determined were included in this study. We excluded patients with insufficient follow-up, those who did not comply with occlusion, and those with co-existing ocular conditions such as retinopathy of prematurity. Results Three females and two males (four right eyes and one left) were followed for a period of 16 months to 7 years. Myopic fundus changes were present in three patients. Glasses were the preferred method of optical correction in four patients; one patient was prescribed a contact lens. Occlusion therapy was used in four of the five patients. Strabismus was present in four. Ipsilateral astigmatism of +2.00 D or more was present in three of the affected eyes. The difference in the spherical equivalent refraction between both eyes in each patient ranged from 5 to 20 diopters. In one patient, we observed the progressive development of unilateral myopia from an initial hypermetropia of +2.00 at age 2 months to myopia of −9.00 at the age of 5 years. Conclusions Unilateral high myopia is probably not present at birth. Our observations support its development in the first few years of life. The results of amblyopia therapy depend on the degree of anisometropia, the co-existence of strabismus, the compliance with penalization, and the presence of retinal abnormalities.