No abstract

ADAMTSL4 is the most important known causative gene in isolated EL. Mutations in ADAMTSL4 appear to cause earlier manifestation of EL and are associated with increased axial length as compared to FBN1. We suggest that ADAMTSL4 be screened in all patients with isolated EL and that physicians be vigilant for the more severe ocular phenotype associated with mutations in this gene.

IMPORTANCE Knobloch syndrome is a rare, recessively inherited disorder classically characterized by high myopia, retinal detachment, and occipital encephalocele, but it is now known to have an increasingly variable phenotype. There is a lack of reported electrophysiologic data, and some key clinical features have yet to be described.OBJECTIVE To expand on current clinical, electrophysiologic, and molecular genetic findings in Knobloch syndrome. DESIGN, SETTING, AND PARTICIPANTSTwelve patients from 7 families underwent full ophthalmic examination and retinal imaging. Further investigations included electroretinography and neuroradiologic imaging. Bidirectional Sanger sequencing of COL18A1 was performed with segregation on available relatives. The study was conducted from July 4, 2013, to October 5, 2015. Data analysis was performed from May 20, 2014, to November 3, 2015. MAIN OUTCOMES AND MEASURESResults of ophthalmic and neuroradiologic assessment and sequence analysis of COL18A1. RESULTSOf the 12 patients (6 males; mean age at last review, 16 years [range, 2-38 years]), all had high myopia in at least 1 eye and severely reduced vision. A sibling pair had unilateral high myopia in their right eyes and near emmetropia in their left eyes from infancy. Anterior segment abnormalities included absent iris crypts, iris transillumination, lens subluxation, and cataract. Two patients with iris transillumination had glaucoma. Fundus characteristics included abnormal collapsed vitreous, macular atrophy, and a tesselated fundus. Five patients had previous retinal detachment. Electroretinography revealed a cone-rod pattern of dysfunction in 8 patients, was severely reduced or undetectable in 2 patients, and demonstrated cone-rod dysfunction in 1 eye with undetectable responses in the other eye in 2 patients. Radiologic imaging demonstrated occipital encephalocele or meningocele in 3 patients, occipital skull defects in 4 patients, minor occipital changes in 2 patients, and no abnormalities in 2 patients. Cutaneous scalp changes were present in 5 patients. Systemic associations were identified in 8 patients, including learning difficulties, epilepsy, and congenital renal abnormalities. Biallelic mutations including 2 likely novel mutations in COL18A1, were identified in 6 families that were consistent with autosomal recessive inheritance with a single mutation identified in a family with 2 affected children. CONCLUSIONS AND RELEVANCEThis report describes new features in patients with Knobloch syndrome, including pigment dispersion syndrome and glaucoma as well as cone-rod dysfunction on electroretinography. Two patients had normal neuroradiologic findings, emphasizing that some affected individuals have isolated ocular disease. Awareness of the ocular phenotype may aid early diagnosis, appropriate genetic counseling, and monitoring for potential complications.

Inherited ectopia lentis (EL) is most commonly caused by Marfan syndrome (MFS), a multisystemic disorder caused by mutations in FBN1. Historically the diagnosis for patients with EL who have no systemic features of MFS is isolated EL (IEL). However, the Ghent nosology for MFS was updated in 2010 and made some important alterations. In particular, patients with EL and a FBN1 mutation are now categorically diagnosed with MFS, if their mutation has previously been described with aortic dilation/dissection. This carries significant systemic implications, as many patients previously diagnosed with IEL are now reclassified. We provide a review of all published cases of IEL caused by FBN1 mutations over the last 20 years to assess what impact the new Ghent nosology has on these. Indeed, 57/123 probands (46.3%) are now classified as MFS according to the revised Ghent nosology and 37/96 mutations (38.5%) reported to cause isolated EL have also been found in patients with aortic dilation/dissection. These findings suggest that EL caused by mutations in FBN1 is actually part of a spectrum of fibrillinopathies with MFS, and the term ‘IEL’ should be avoided in such cases.

PurposeSilicone oil is the most common choice of tamponade agent used when managing a giant retinal tear (GRT). Concern exists regarding its potential detrimental effect on vision. We herein report on visual and surgical outcomes of all patients treated at Moorfields Eye Hospital for a GRT over a five year period. We further analysed a subgroup of fovea-sparing retinal detachments (RD) treated by pars plana vitrectomy (PPV) with either silicone oil or gas tamponade.MethodsRetrospective comparative, non-randomised, cross-sectional review of patients with a new diagnosis of GRT from 1 September 2005 to 31 August 2010ResultsOne hundred twenty four eyes of 118 patients were identified with mean age of 45.5 years and median follow-up of 24 months. Subgroup analysis of fovea-sparing RDs (Silicone Oil n=49, Gas n=15) revealed visual loss (≥2 Snellen Lines of vision) in 49.0% (n=24) of patients managed with oil compared to 13.3% (n=2) of gas patients (P=0.019). In all, 73.3% (n=11) in the gas group achieved a final vision of 6/12 or better, compared to 36.7% (n=18) in the oil group (P=0.031). No difference was observed in eventual or primary anatomical success rate (100 vs 93.9%, and 66.7 vs 79.6%, gas vs oil, respectively, (P>0.1)). Postoperative complications were absent in 66.7% (n=10) of gas patients compared with 14.3% (n=7) of oil patients (P=0.002). Multiple variable linear regression determined tamponade choice as the only variable predictive of final visual acuity (P=0.046).ConclusionEyes with fovea-sparing GRT-related RDs managed with gas achieved a better visual outcome with fewer postoperative complications and no significant difference in anatomical success. A multicentre approach to investigate this further is advised.

No abstract

Ectopia lentis (EL) is a condition that can either herald underlying systemic conditions, or be isolated. The recent expansion in the genetics of these conditions has furthered the understanding of the underlying molecular aetiology. It is becoming apparent that novel genes, and in particular the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family, are important in ocular development. The common link in these genes seems to be EL. The clinical management of EL is challenging. In particular, the options for addressing surgically induced aphakia in the context of an ectopic capsule are varied. Little evidence exists to direct management of these issues. This review summarises the molecular pathogenesis of EL and conditions associated with it, using the genetic aetiology as a framework. Furthermore, it summarises some of the issues involved in its clinical management.

No abstract