Leon Au

Mutations in PRDM5 in Brittle Cornea Syndrome Identify a Pathway Regulating Extracellular Matrix Development and Maintenance

Extreme corneal fragility and thinning, which have a high risk of catastrophic spontaneous rupture, are the cardinal features of brittle cornea syndrome (BCS), an autosomal-recessive generalized connective tissue disorder. Enucleation is frequently the only management option for this condition, resulting in blindness and psychosocial distress. Even when the cornea remains grossly intact, visual function could also be impaired by a high degree of myopia and keratoconus. Deafness is another common feature and results in combined sensory deprivation. Using autozygosity mapping, we identified mutations in PRDM5 in families with BCS. We demonstrate that regulation of expression of extracellular matrix components, particularly fibrillar collagens, by PRDM5 is a key molecular mechanism that underlies corneal fragility in BCS and controls normal corneal development and maintenance. ZNF469, encoding a zinc finger protein of hitherto undefined function, has been identified as a quantitative trait locus for central corneal thickness, and mutations in this gene have been demonstrated in Tunisian Jewish and Palestinian kindreds with BCS. We show that ZNF469 and PRDM5, two genes that when mutated cause BCS, participate in the same regulatory pathway.

Manchester iStent study: early results from a prospective UK case series

To evaluate the 6‐month efficacy and safety of the iStent microtrabecular bypass stent in patients with open‐angle glaucoma.

Brittle cornea syndrome: recognition, molecular diagnosis and management.

Brittle cornea syndrome (BCS) is an autosomal recessive disorder characterised by extreme corneal thinning and fragility. Corneal rupture can therefore occur either spontaneously or following minimal trauma in affected patients. Two genes, ZNF469 and PRDM5, have now been identified, in which causative pathogenic mutations collectively account for the condition in nearly all patients with BCS ascertained to date. Therefore, effective molecular diagnosis is now available for affected patients, and those at risk of being heterozygous carriers for BCS. We have previously identified mutations in ZNF469 in 14 families (in addition to 6 reported by others in the literature), and in PRDM5 in 8 families (with 1 further family now published by others). Clinical features include extreme corneal thinning with rupture, high myopia, blue sclerae, deafness of mixed aetiology with hypercompliant tympanic membranes, and variable skeletal manifestations. Corneal rupture may be the presenting feature of BCS, and it is possible that this may be incorrectly attributed to non-accidental injury. Mainstays of management include the prevention of ocular rupture by provision of protective polycarbonate spectacles, careful monitoring of visual and auditory function, and assessment for skeletal complications such as developmental dysplasia of the hip. Effective management depends upon appropriate identification of affected individuals, which may be challenging given the phenotypic overlap of BCS with other connective tissue disorders.

The New Era of Glaucoma Micro-stent Surgery

Minimally invasive glaucoma surgery (MIGS) has been gaining popularity over the last decade. Although there is no strict definition for MIGS, all the new procedures share the common theme of intraocular pressure reduction with minimal tissue destruction, short surgical time, simple instrumentation and fast postoperative recovery. The use of glaucoma drainage implants has long been the traditional treatment for complex glaucoma, but a new wave of glaucoma micro-stents are now being manufactured with various materials designed to increase aqueous outflow via different channels. This review summarises the current published literature on these devices, including Sclemm’s canal stents (iStent, Hydrus), Suprachoroidal stents (CyPass, iStent supra), and subconjunctival stents (Xen, Innfocus).

Use of iris recognition camera technology for the quantification of corneal opacification in mucopolysaccharidoses

Mucopolysaccharidoses (MPS) can cause corneal opacification that is currently difficult to objectively quantify. With newer treatments for MPS comes an increased need for a more objective, valid and reliable index of disease severity for clinical and research use. Clinical evaluation by slit lamp is very subjective and techniques based on colour photography are difficult to standardise. In this article the authors present evidence for the utility of dedicated image analysis algorithms applied to images obtained by a highly sophisticated iris recognition camera that is small, manoeuvrable and adapted to achieve rapid, reliable and standardised objective imaging in a wide variety of patients while minimising artefactual interference in image quality.

Are newer surgical interventions for glaucoma making a difference

Over the last few years, there has been an explosion of new surgical treatments for glaucoma. They all promise maximum safety, minimal invasion, combined with good efficacy in the control of glaucoma. There are a range of ab interno interventions and devices that aim to increase aqueous outflow. The Trabectome (NeoMedix, USA) is designed to remove a large section of trabecular meshwork, exposing collector channels and increasing outflow. The iStent (Glaukos, USA) and Hydrus (Ivantis, USA) are both devices that are inserted into Schlemms canal ab interno, bypassing trabecular meshwork resistance. The Xen implant (Aquesys, USA) is another ab interno device that is inserted through the trabecular angle into the subconjunctival space, creating an external drainage fistula similar in concept to a trabeculectomy. High intensity focused ultrasound (HIFU, Eyetechcare, France), a technology previously used successfully in the treatment of prostate cancer, has recently been adopted in glaucoma to ablate the ciliary body. In this issue of BJO , we look at another potential ‘gold mine’ for glaucoma treatment—the suprachoroidal space. There has been a resurgence of interest in exploring the potential of directing aqueous into the suprachoroidal space by means of ab interno drainage devices. Saheb and colleagues from Canada examined the CyPass Micro-Stent (Transcend Medical, USA) …

Outcome of bleb revision using scleral patch graft and conjunctival advancement.

PurposeTo evaluate our surgical technique of bleb revision using scleral patch graft and conjunctival advancement, the long-term outcome and the ability to maintain adequate intraocular pressure (IOP) control. Patient and MethodsRetrospective review. ResultsEighteen patients were identified. The mean age was 72.1±4.3 years (95% confidence limits). In 12 of the 18 cases, the posterior edge of scleral patch graft was secured with fixed sutures, in another 3 with releasable sutures and in the remaining 3 with adjustable sutures. The mean follow-up period was 23.7±5.4 months (95% confidence limits). The mean preoperative IOP was 7.6±3.0 mm Hg (95% confidence limits), increased to 13.1±1.6 mm Hg (P=0.02) postoperatively. Twelve of the 18 patients had a minimum of 2-year follow-up. At this time point, 7 out of 12 (58%) patients had IOP <21 mm Hg without any medication, 9 out of 12 (75%) patients had IOP <21 mm Hg with medication, 7 out of 12 (58%) patients had IOP <16 mm Hg without medication, and 9 out of 12 (75%) had IOP <16 mm Hg with medication. The mean number of 5-fluorouracil injections with or without needling was significantly higher in the success group than in the failure group (P=0.035). ConclusionsThis series illustrates a useful technique using a scleral patch graft in cases of full-thickness scleral defect encountered during bleb revisions. The success rates achieved are comparable to those in the published literature, and furthermore our successful cases achieved lower IOPs appropriate for patients with advanced glaucoma.

I-Stent for treatment of angle recession with raised intraocular pressure.

The I-Stent (Glaukos Corp. Laguna Hills, CA, USA) is a titanium trabecular micro-bypass stent that is implanted into Schlemm’s canal in order to facilitate aqueous outflow in patients with glaucoma. Studies have described its safety and efficacy in the treatment of primary open angle glaucoma. To our knowledge, its use specifically in angle recession glaucoma has not yet been described. We report two such cases.

The use of anterior segment optical coherence tomography in glaucoma drainage implant surgery.

Anterior segment optical coherence tomography is a rapid, non-contact method of assessing anterior segment structures and has high reliability and repeatability. Three cases are presented to illustrate how this technology can be used in the assessment and management of a glaucoma drainage implant. Anterior segment optical coherence tomography provides high-resolution images of the glaucoma drainage implant to assess its position, patency, drainage, and the intraluminal stenting suture. This proved to be useful in the case of postoperative hypotony. The non-contact advantage is useful in pediatric patients.

Long-Term Outcomes and Complications of Baerveldt Glaucoma Drainage Implants in Adults with Glaucoma Secondary to Uveitis

ABSTRACT Purpose: This study investigated the efficacy and safety of Baerveldt glaucoma implants (BGI) in adults with uveitic glaucoma (UG) at the Manchester Uveitis Clinic. Methods: This was a retrospective study of 42 patients with UG who underwent BGI implantation between 2006 and 2015. Primary outcome measures were intraocular pressure (IOP) reduction and number of medications at 5-year follow-up. Three IOP success criteria were chosen: 1.IOP ≤21 mmHg and ≥20% reduction from baseline 2.IOP ≤17 mmHg and ≥20% reduction from baseline and 3.IOP ≤14 mmHg. Results: The mean pre-operative IOP was 29.5 ± 9.5 mmHg on 3.9 antiglaucoma drops. At 5-year follow-up, IOP reduced to 14.4 ± 7.0 mmHg (p < 0.005) on 1.4 drops. The cumulative probability of failure at 5 years based on criteria 1, 2, and 3 was 24.3%, 39.6%, and 56.3%, respectively. Conclusion: This study demonstrated that BGI are safe and effective in refractory UG, especially in younger adults with complex uveitis.