Martin P Snead

Martin P Snead
University of Cambridge | Cam · Brain Repair Centre

MA MD DO FRCS FRCOphth

About

141
Publications
28,353
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
3,418
Citations
Introduction
I have a special interest in all aspects of retinal and vitreous surgery.I lead the Vitreoretinal Research Group at the van Geest Brain Repair Centre, University of Cambridge investigating the molecular pathology of retinal detachment, particularly familial retinal detachment and the Stickler syndromes. I am the service lead for the NHS England nationally commissioned Highly Specialised Services diagnostic service for patients and families with this disorder.

Publications

Publications (141)
Article
Full-text available
The fibrillar collagen family is comprised of the quantitatively major types I, II and III collagens and the quantitatively minor types V and XI. These form heterotypic collagen fibrils (composed of more than a single collagen type) where the minor collagens have a regulatory role in controlling fibril formation and diameter. The structural pre-req...
Article
Full-text available
Stickler syndromes are inherited conditions caused by abnormalities of structural proteins in the eye, inner ear and cartilage. The risk of retinal detachment, particularly due to the development of giant retinal tears, is high. Stickler syndrome is the most common cause of childhood retinal detachment. Although retinal detachment surgery in the ge...
Article
Full-text available
Stickler syndrome (SS) is a genetic disorder with manifestations in the eye, ear, joints, face and palate. Usually inherited in a dominant fashion due to heterozygous pathogenic variants in the collagen genes COL2A1 and COL11A1, it can rarely be inherited in a recessive fashion from variants in COL9A1, COL9A2, and COL9A3, COL11A1, as well as the no...
Article
Full-text available
Diagnostic genetics within the United Kingdom National Health Service (NHS) has undergone many stepwise improvements in technology since the completion of the human genome project in 2003. Although Sanger sequencing has remained a cornerstone of the diagnostic sequencing arena, the human genome reference sequence has enabled next-generation sequenc...
Article
Full-text available
The Stickler syndromes are a group of genetic connective tissue disorders associated with an increased risk of rhegmatogenous retinal detachment, deafness, cleft palate, and premature arthritis. This review article focuses on the molecular genetics of the autosomal dominant forms of the disease. Pathogenic variants in COL2A1 causing Stickler syndro...
Article
The interface between silicone oil and saline layers in a 3D model of the eye chamber was studied under different eye-like saccadic motions in order to determine the stability of the interface and propensity for emulsification in the bulk. The effect of level of fill; saccade amplitude, angular velocity, latency time; and orientation were investiga...
Article
Full-text available
In 2011 NHS England commissioned a new national specialist MDT service for patients and families affected by Stickler syndrome. The Stickler syndromes form part of the spectrum of inherited vitreoretinopathies and are the most common cause of retinal detachment in childhood and the most common cause of familial retinal detachment. Now in its 10th y...
Article
Full-text available
Purpose: To present the extent and site of lesion of auditory dysfunction in a large cohort of individuals with type 2 Stickler Syndrome. Type 2 Stickler Syndrome results from a mutation in the gene coding for α-1 type XI pro-collagen, which has been identified in the human vitreous, cartilage and the cochlea of the mouse. The condition is charact...
Article
Full-text available
Recent reports suggest that the use of an outpatient-based procedure (pneumatic retinopexy, PR) for retinal detachment repair should be encouraged within the UK, especially in light of Covid-19 and possible restrictions/competing demands on access to operating theatres. It is therefore essential that patients receive comprehensive information about...
Chapter
Stickler syndrome
Chapter
incidence and trends in retinal detachment in UK
Article
Full-text available
Purpose Emulsification of silicone oil (SiOil) in a vitrectomized eye was investigated using a 3D model of the vitreous cavity to test the hypothesis that oil droplet formation arises from the breakdown of the bulk SiOil‐aqueous interface during eye saccadic movement. Methods Round bottom flasks filled with SiOil and a saline phase modelled the vi...
Article
Full-text available
Background Type 2 Stickler syndrome is usually a dominant disorder resulting from pathogenic variants in COL11A1 encoding the alpha 1 chain of type XI collagen. Typical molecular changes result in either substitution of an obligate glycine within the Gly‐Xaa‐Yaa amino acid sequence repeat region of the molecule, mRNA missplicing or deletions/duplic...
Article
Full-text available
The key to successful management of rhegmatogenous retinal detachment (RRD) is to find and seal all of the retinal breaks, and the two main surgical techniques used to achieve this are scleral bucking (SB) or pars plana vitrectomy (PPV). Techniques for SB have remained mostly unchanged for the last 60 years, whilst PPV techniques and instruments ha...
Article
Full-text available
The Stickler syndromes are the leading cause of inherited retinal detachment and the most common cause of rhegmatogenous retinal detachment in childhood. The clinical and molecular genetic spectrum of this connective tissue disorder is discussed in this article, emphasising the key role the ophthalmologist has to play in the identification, diagnos...
Article
Full-text available
Background: Patients with Stickler syndrome often require emergency surgery and are often anesthetized in nonspecialist units, typically for retinal detachment repair. Despite the occurrence of cleft palate and Pierre-Robin sequence, there is little published literature on airway complications. Our aim was to describe anesthetic practice and compl...
Article
Stickler syndrome (SS) is characterized by ophthalmic, articular, orofacial, and auditory manifestations. SS is usually autosomal dominantly inherited with variants in COL2A1 or COL11A1. Recessive forms are rare but have been described with homozygous variants in COL9A1, COL9A2, and COL9A3 and compound heterozygous COL11A1 variants. This article ex...
Article
Full-text available
Stickler syndrome is a genetic disorder that can lead to joint problems, hearing difficulties and retinal detachment. Genes encoding collagen types II, IX and XI are usually responsible, but some families have no causal variant identified. We investigate a variant in the gene encoding growth factor BMP4 in a family with Stickler syndrome with assoc...
Article
Full-text available
Stickler syndrome is a genetic disorder that can lead to joint problems, hearing difficulties and retinal detachment. Genes encoding collagen types II, IX and XI are usually responsible, but some families have no causal variant identified. We investigate a variant in the gene encoding growth factor BMP4 in a family with Stickler syndrome with assoc...
Article
Aim: To review the radiological findings of the largest cohort to date of paediatric patients with Stickler syndrome, all with confirmed molecular genetic analysis and sub-typing. Patients and methods: It is understood that the National Health Service (NHS) commissioned service at Addenbrookes Hospital, Cambridge, UK has the largest cohort of St...
Article
Full-text available
Osteogenesis imperfecta (OI) is a rare primarily autosomal dominant condition in which the connective tissues of bones, ligaments and sclerae do not form properly. Typically, mutations in COL1A1 and COL1A2 genes lead to the defective formation or quantity of type I collagen, the principle matrix in these tissues. Molecular genetic studies have now...
Article
Full-text available
Background: Osteogenesis imperfecta (OI) is a rare primarily autosomal dominant condition in which the connective tissues of bones, ligaments and sclerae do not form properly. Typically, mutations in COL1A1 and COL1A2 genes lead to the defective formation or quantity of type I collagen, the principle matrix in these tissues. Molecular genetic stud...
Article
Background Osteogenesis imperfecta (OI) is a rare primarily autosomal dominant condition in which the connective tissues of bones, ligaments and sclerae do not form properly. Typically, mutations in COL1A1 and COL1A2 genes lead to the defective formation or quantity of type I collagen, the principle matrix in these tissues. Molecular genetic studie...
Article
Full-text available
Purpose: Despite posterior vitreous detachment being a common ocular event affecting most individuals in an aging population, there is little consensus regarding its precise anatomic definition. We investigated the morphologic appearance and molecular composition of the posterior hyaloid membrane to determine whether the structure clinically obser...
Article
Full-text available
Anterior segment dysgeneses (ASDs) comprise a spectrum of developmental disorders affecting the anterior segment of the eye. Here, we describe three unrelated families affected by a previously unclassified form of ASD. Shared ocular manifestations include bilateral iris hypoplasia, ectopia lentis, corectopia, ectropion uveae, and cataracts. Whole-e...
Article
Purpose: To report a case of bilateral intraocular hemorrhage secondary to cerebral venous sinus thrombosis with no associated intracranial hemorrhage. Methods: Case report. Results: A 32-year-old Asian gentleman presented with left reduced vision as a result of a left subhyaloid macular hemorrhage associated with severe headache. Right retina...
Article
Full-text available
COL2A1 mutations causing haploinsufficiency of type II collagen, cause type 1 Stickler syndrome which has a high risk of retinal detachment and failure of the vitreous to develop normally. Exon 2 of COL2A1 is alternatively spliced, expressed in the eye but not in mature cartilage and encodes a region that binds growth factors TGFβ1 and BMP-2. We in...
Article
Importance: In-the-bag intraocular lens dislocation is an uncommon but serious complication of cataract surgery in patients with previous repair of retinal detachment. The causative mechanism is currently unknown. We report histologic findings from a retrospective case series from 1993 to 2010 and suggest a possible mechanism to explain this assoc...
Article
PurposeTo study the variability of the ophthalmic phenotype in Kniest dysplasia. Kniest dysplasia is an inherited disorder associated with defects in type II collagen and characterised by short-trunked dwarfism, kyphoscoliosis, and enlarged joints with restricted mobility. Other features include marked hand arthropathy, cleft palate, hearing loss,...
Chapter
Inherited vitreoretinopathies mostly result from genetic abnormalities of types II, IX, or V/XI collagen [see chapter I. A. Vitreous proteins] and proteoglycans, [see chapters I.B. Vitreous GAGs and I. F. Vitreous biochemistry and artificial vitreous] expressed principally and collectively in the eye but also in articular and hyaline cartilage. The...
Article
Full-text available
Purpose The Stickler syndromes are the most common causes of inherited and childhood retinal detachment; however, no consensus exists regarding the effectiveness of prophylactic intervention. We evaluate the long-term safety and efficacy of the Cambridge prophylactic cryotherapy protocol, a standardized retinal prophylactic treatment developed to p...
Chapter
Inherited Vitreoretinopathies and molecular genetic analysis
Article
Full-text available
Stickler syndromes types 1, 2 and 3 are usually dominant disorders caused by mutations in the genes COL2A1, COL11A1 and COL11A2 that encode the fibrillar collagens types II and XI present in cartilage and vitreous. Rare recessive forms of Stickler syndrome exist that are due to mutations in genes encoding type IX collagen (COL9A1 type 4 Stickler sy...
Article
Full-text available
Background COL11A1 is a large complex gene around 250 kb in length and consisting of 68 exons. Pathogenic mutations in the gene can result in Stickler syndrome, Marshall syndrome or Fibrochondrogenesis. Many of the mutations resulting in either Stickler or Marshall syndrome alter splice sites and result in exon skipping, which because of the exon s...
Article
Full-text available
Rhegmatogenous retinal detachment (RRD) is an important cause of vision loss and can potentially lead to blindness. The underlying pathogenesis is complex and incompletely understood. We applied a two-stage genetic association discovery phase followed by a replication phase in a combined total of 2,833 RRD cases and 7,871 controls. The discovery ph...
Article
Mutations in COL2A1, the gene for type II-collagen, can result in a wide variety of phenotypes depending upon the nature of the mutation. Dominant negative mutations tend to result in severe and often lethal skeletal dysplasias such as achondrogenesis type 2, Kniest dysplasia, and spondyloepiphyseal dysplasia congenita. Stickler syndrome, a conditi...
Article
Full-text available
UK NHS diagnostic service sequence analysis of genes generally examines and reports on variations within a designated region 5' and 3' of each exon, typically 30 bp up and downstream. However, because of the degenerate nature of the splice sites, intronic variants outside the AG and GT dinucleotides of the acceptor and donor splice sites (ASS and D...
Article
Full-text available
The entity described by Gunnar Stickler, which included hereditary arthro-ophthalmopathy associated with retinal detachment, has recently been recognised to consist of a number of subgroups, which might now more correctly be referred to as the Stickler syndromes. They are the most common clinical manifestation of the type II/XI collagenopathies and...
Article
Stickler syndrome is a dominantly inherited disorder affecting the fibrillar type II/XI collagen molecules expressed in vitreous and cartilage. Mutations have been found in COL2A1, COL11A1 and COL11A2. It has a highly variable phenotype that can include midline clefting, hearing loss, premature osteoarthritis, congenital high myopia and blindness t...
Article
Isolated motor third, fourth or sixth nerve palsies are a well recognized complication following botulinum toxin injection for hemifacial spasm or essential blepharospasm. A case of hemifacial spasm secondary to giant aneurysm of the internal carotid artery is reported, stressing the importance of further investigation if such neurological sequelae...
Article
Eye is the official journal of the Royal College of Ophthalmologists. It aims to provide the practising ophthalmologist with information on the latest clinical and laboratory-based research.
Article
For rhegmatogenous retinal detachment, reattachment with a single procedure is associated with better visual outcomes. In the past, silicone oil has been used mostly as a last resort following failed primary surgery. This study evaluates a novel approach to patients at high risk of primary failure, using silicone tamponade as the primary stage of a...
Article
Full-text available
Separation of the vitreous and posterior hyaloid membrane (PHM) or posterior vitreous detachment (PVD) typically occurs between the ages of 45 and 65 years in the general population, but may occur earlier in myopic or otherwise predisposed individuals. Age-related synergetic changes occurring within the cortical and central gel must be distinguishe...
Article
Full-text available
Purpose/background: Epiretinal membrane (ERM) formation is a common change resulting in disturbance of macular vision and predisposing to rhegmatogenous retinal detachment. Current treatment strategies rely chiefly on surgical removal of the membranes from the surface of the retina, allowing the retina to remodel and reattach. Improved knowledge o...
Article
Full-text available
This paper will illustrate how variation in the processing of mutant pre-mRNA can affect the phenotypic outcome of inherited disorders of type II collagen. Type 1 Stickler's syndrome is one of the different phenotypes resulting from mutations in COL2A1 (the type II collagenopathies). It is also the commonest, but often goes undiagnosed due to the v...
Article
The use of adjunctive scleral buckling during vitrectomy for retinal detachment associated with inferior breaks has been the recent focus of some debate. It has been suggested that any benefit might be outweighed by potential complications associated with buckling surgery. The purpose of this study was to compare the success rate of vitrectomy, gas...