Genetic analysis of strictly defined Leber congenital amaurosis with (and without) neurodevelopmental delay.

BACKGROUND: Leber congenital amaurosis (LCA) is a severe infantile retinal dystrophy that is non-syndromic other than neurodevelopmental delay, reported in up to 20% of cases according to one older study. The phenotype is typically autosomal recessive and is genetically heterogeneous. Although LCA is defined by a non-recordable electroretinogram (ERG) during infancy, many LCA studies include infants with low ERG readings and/or older children not phenotyped during infancy. More recent series of genetically confirmed LCA do not document the recurrent neurodevelopmental delay of older studies. We investigate the possibility that neurodevelopmental delay is not actually a recurrent feature of strictly defined otherwise non-syndromic LCA. METHODS: Retrospective consecutive case series (2012-2014) of children with strictly defined LCA, all of whom underwent targeted next-generation sequencing with a panel of 14 LCA genes. RESULTS: All families were endogamous and/or consanguineous. 18/19 (22/23 children) had detectable causative recessive mutations, and these were in one of three genes only: 11 in RPGRIP1, 5 in GUCY2D and 2 in RPE65. 9/11 children with RPGRIP1 mutations harboured homozygous c.1007delA (p.Glu370Asnfs*5) mutation. 5/23 children (22%) had concomitant neurodevelopmental delay, and these five children harboured recessive mutations in RPGRIP1 (2) or GUCY2D (3). Haplotype analysis for cases with the RPGRIP1 deletion suggested a single ancestral mutation. CONCLUSIONS: Neurodevelopmental delay is a potential feature of strictly defined LCA, documented in our series for some children with homozygous RPGRIP1 and GUCY2D mutations. Strictly defining LCA can limit genetic heterogeneity. On the Arabian Peninsula, the phenotype is frequently from recessive RPGRIP1 mutations, most of which are a founder RPGRIP1 deletion.

Primary and secondary congenital glaucoma: baseline features from a registry at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.

PURPOSE: To compare the demographic and clinical distribution of primary and secondary congenital glaucoma from a registry at King Khaled Eye Specialist Hospital. DESIGN: Registry-based cohort study. METHODS: Review of registry data that included new patients with congenital glaucoma seen between 2001 and 2003 (29 months); analysis of the demographic data and clinical features of primary and secondary congenital glaucoma at presentation. RESULTS: A total of 325 eyes of 180 patients were included. Most patients had primary congenital glaucoma (80%). The mean (± SD) age at presentation for primary congenital glaucoma was 3.8 ± 10.7 months and for secondary congenital glaucoma was 4.3 ± 7.9 months. Most primary congenital glaucoma and secondary congenital glaucoma patients had bilateral disease (82.6%; 74.3%). Primary congenital glaucoma was equally distributed by sex but secondary congenital glaucoma was 1.5-fold more common in male patients. A positive family history was elicited in 30%, and almost 60% had a history of consanguinity in both groups. The mean intraocular pressure and corneal diameter were comparable in both groups but the axial length was significantly longer in primary congenital glaucoma and cup-to-disc (C/D) ratio greater in secondary congenital glaucoma. In the primary congenital glaucoma group, corneal haze showed a significant relationship with most clinical parameters. In primary congenital glaucoma, a positive correlation was noted between age at presentation and increasing corneal diameter and axial length but a negative relationship was noted with C/D ratio and corneal haze, whereas for secondary congenital glaucoma only axial length was positively correlated. CONCLUSION: The congenital glaucoma registry provides unique baseline data on primary congenital glaucoma and secondary congenital glaucoma in Saudi Arabia that will enable us to better understand the disease in the Kingdom and region.

Update of intraocular lens implantation in children.

Cataract is a common problem that affects the vision in children and a major cause of amblyopia in children. However, the management of childhood cataract is tenuous and requires special considerations especially with regard to intraocular lens (IOL) implantation. Age at which an IOL can be implanted is a controversial issue. Implanting an IOL in very young children carries the risk of severe postoperative inflammation and posterior capsule opacification that may need other surgeries and may affect the vision permanently. Accuracy of the calculated IOL power is affected by the short eyes and the steep keratometric values at this age. Furthermore, choosing an appropriate IOL power is not a straight forward decision as future growth of the eye affects the axial length and keratometry readings which may result in an unexpected refractive error as children age. The aim of this review is to cover these issues regarding IOL implantation in children; indications, timing of implantation, types of IOLs, site of implantation and the power calculations.

Ocular manifestations of branchio-oculo-facial syndrome: report of a novel mutation and review of the literature.

PURPOSE: To report unusual ocular manifestations of branchio-oculo-facial syndrome (BOFS) caused by a novel mutation in activating enhancer binding protein 2 alpha (TFAP2A). METHODS: Full ophthalmological evaluation and direct sequencing of TFAP2A. RESULTS: A 10-year-old girl with unusual ocular manifestations of BOFS such as elliptical shaped microcornea and a novel de novo TFAP2A mutation was identified. CONCLUSIONS: This report expands the ocular phenotypic spectrum of BOFS and adds to the small number of reported TFAP2A mutations.

Familial ptotic lid elevation during ipsilateral abduction.

PURPOSE: To report and discuss the clinical findings of a 17-member family with 2 siblings who exhibit ptosis and abnormal synkinetic lid elevation associated with ipsilateral abduction. SUBJECTS AND METHODS: Sixteen members of the 17-member immediate family underwent ophthalmic examination. RESULTS: Two siblings exhibited ptosis and abnormal synkinetic lid elevation associated with ipsilateral abduction. One was bilaterally affected and the other had unilateral findings. A third sibling had isolated bilateral congenital ptosis. A fourth demonstrated classic Duane syndrome Type I in the right eye. Other family members did not have ophthalmic abnormalities. CONCLUSIONS: A unifying mechanism of congenital cranial dysinnervation may underlie these and similar phenotypes of oculomotor and/or abducens nerve abnormalities with or without abnormal synkinesis.

Large-segment superior oblique tendon expanders in the management of severe congenital Brown syndrome.

PURPOSE: To report the effectiveness of large-segment superior oblique tendon expanders for severe congenital Brown syndrome. METHODS: Medical records of 12 consecutive patients with severe congenital Brown syndrome were evaluated retrospectively. All patients had a hypotropia > 20 prism diopters in primary position. A superior oblique tendon lengthening procedure, using a 10- to 12-mm-long silicone band, was performed on each patient. Preoperative and postoperative extraocular motility patterns were analyzed, and the final results were graded as "excellent," "good," "fair," "poor, undercorrected" and "poor, overcorrected." RESULTS: As of the last recorded follow-up examination (mean, 32 months), three patients had an excellent result, six had a good result, three had a fair result, and none had a poor result. All patients experienced an improvement in their severe Brown syndrome, with 100% showing a postoperative primary-position hypotropia < 8 prism diopters. Postoperative limitation of elevation in adduction was either -1 or -2 for all patients. No patient required further surgery, and no extrusions of the implants were noted. CONCLUSION: The superior oblique tendon expander procedure appears to be an effective tool in the surgical treatment of severe Brown syndrome. The use of a large-segment (10- to 12-mm) band seems to be an appropriate choice when dealing with patients having primary-position hypotropia > 20 prism diopters.

Results of surgery for bilateral cataract associated with sensory nystagmus in children.

PURPOSE: To report the outcome of cataract surgery in children with bilateral cataract and preoperative sensory nystagmus. DESIGN: Interventional case series. METHODS: Retrospective review of 95 children who underwent surgery for bilateral cataract associated with sensory nystagmus. All patients lacked other structural ocular defects or neurologic abnormalities and were old enough at last follow-up to cooperate with recognition visual acuity testing. Outcome parameters studied were best-corrected postoperative visual acuity of the better eye and postoperative reduction or elimination of nystagmus. RESULTS: Mean age at surgery +/- SD was 2.0 +/- 2.6 years (range, 1 month to 13 years). Mean follow-up was 6.1 +/- 3.4 years (range, 2 months to 15 years). Best-corrected postoperative visual acuity of the better eye ranged from 20/25 to counting fingers and was 20/60 or better in 44 (46%), between 20/60 and 20/200 in 37 (39%), and 20/200 or worse in 14 (15%). Preoperative recognition visual acuity data were available for 16 of the older patients, and 5 or more lines of visual acuity improvement occurred in 5 (31%) including children as old as 9 years at the time of surgery. Nystagmus was reduced or eliminated postoperatively in 38 (40%). Mild, as opposed to severe, preoperative nystagmus was predictive of both a better visual acuity outcome (P =.004) and reduced or eliminated nystagmus postoperatively (P =.02). CONCLUSIONS: Good or even excellent visual acuity can be achieved after cataract surgery in some children with bilateral cataract and sensory nystagmus, and the nystagmus sometimes improves postoperatively.