Reduced bone mineral density and hyaloid vasculature remnants in a consanguineous recessive FEVR family with a mutation in LRP5.

BACKGROUND/AIMS: Familial exudative vitreoretinopathy (FEVR) is an inherited blinding condition characterised by abnormal development of the retinal vasculature. FEVR has multiple modes of inheritance, and homozygous mutations in LRP5 have recently been reported as underlying the recessive form of this disease. The aim of this study was to examine LRP5 in a consanguineous recessive FEVR family and to clarify the eye and bone phenotype associated with recessive FEVR. METHODS: All family members were examined by slit lamp biomicroscopy and indirect ophthalmoscopy. Linkage to LRP5 was determined by genotyping microsatellite markers, constructing haplotypes and calculating lod scores. Mutation screening of LRP5 was performed by polymerase chain reaction amplification of genomic DNA followed by direct sequencing. Bone mineral density (BMD) was evaluated in all family members using dual energy x ray absorptiometry (DEXA). RESULTS: The clinical features observed in this family were consistent with a diagnosis of recessive FEVR. A homozygous LRP5 missense mutation, G550R, was identified in all affected individuals and all unaffected family members screened were heterozygous carriers of this mutation. Reduced BMD, hyaloid vasculature remnants, and nystagmus were features of the phenotype. CONCLUSION: Recessive mutations in LRP5 can cause FEVR with reduced BMD and hyaloid vasculature remnants. Assessment of a patient with a provisional diagnosis of FEVR should therefore include investigation of BMD, with reduced levels suggestive of an underlying LRP5 mutation.

Familial exudative vitreoretinopathy and related retinopathies.

Familial exudative vitreoretinopathy (FEVR) is a rare inherited disorder of retinal angiogenesis. Cases can be autosomal dominant, autosomal recessive, or X-linked. FEVR patients have an avascular peripheral retina which, depending on the degree of ischaemia, causes the secondary complications of the disease. Expressivity may be asymmetric and is highly variable. Five genes have been identified that when mutated, cause FEVR; NDP (X-linked), FZD4 (autosomal dominant and recessive), LRP5 (autosomal dominant and recessive), TSPAN12 (autosomal dominant and recessive), and ZNF408 (autosomal dominant). Four of these genes have been shown to have a central role in Norrin/Frizzled4 signalling, suggesting a critical role for this pathway in retinal angiogenesis. In addition to the ocular features, LRP5 mutations can cause osteopenia and osteoporosis. All FEVR patients in whom molecular testing is not easily accessible should have dual energy X-ray absorptiometry (DEXA) scans to assess bone mineral density, as treatment can be initiated to reduce the risk of bone fractures.

Trans-orbital intra-cranial air gun injury.

PURPOSE: To describe a case of trans-orbital intra-cranial air gun injury with a discussion on air gun related morbidity and mortality. METHODS: Case report and literature review. RESULTS: The air gun pellet travelled through the orbit without penetrating the globe. It passed into the middle cranial fossa through the superior orbital fissure and lodged in the temporal lobe. The patient was managed conservatively with antibiotics and antiepilectis. CONCLUSIONS: Air gun design has changed in recent years resulting in an increased morbidity and mortality. Stricter legislation on the sale and use of these weapons needs to be implemented.

Viscocanalostomy versus trabeculectomy for primary open angle glaucoma: 4-year prospective randomized clinical trial.

AIMS: The purpose of this randomized clinical trial was to compare the effectiveness and safety of viscocanalostomy (visco) with trabeculectomy (trab) in the management of primary open angle glaucoma (POAG). METHODS: Patients were randomized to have a viscocanalostomy (25 eyes) or a trabeculectomy (25 eyes) performed by one surgeon (TDM) and followed up prospectively. Patients were examined preoperatively, at day 1, day 3 if required, day 6, week 2 and thereafter as near as possible to 1, 3, 6, 12, 18, 24, 30, 36, 48, 54, and 60 months. We recorded intraocular pressure (IOP), presence or absence of any complications, presence and description of any bleb, visual acuity with glasses, and full examinations as routine to monitor any progression of the glaucoma. Bleb interventions including needling and antimetabolites were allowed and recorded in both groups. YAG laser goniopuncture was allowed in the viscocanalostomy group. RESULTS: Mean follow-up was 40 months (SD 15), with a range from 6 to 60 months. Forty-two percent (n=10) of the patients in the trabeculectomy group had a successful outcome (IOP<18 mm Hg with no treatment) at last follow-up visit, compared to 21% (n=5) in the viscocanalostomy group. IOP was lower in the trab group with differences in IOP being statistically significant at month 12 (P=<0.001), 24 (P=<0.001), 30 (P=0.030), 36 (P=<0.001), and 48 (P=0.018). The trabeculectomy group required less postoperative topical IOP-lowering medication (P=0.011). CONCLUSION: In this study, we found trabeculectomy to be more effective at lowering IOP than viscocanalostomy in POAG patients.