Aims To report long term visual outcomes, complications and graft survival of patients undergoing deep anterior lamellar keratoplasty (DALK) to treat corneal scarring secondary to herpes simplex virus (HSV) keratitis. Methods Retrospective, non-comparative case series. 18 patients who underwent DALK for HSV keratitis related corneal scarring between January 2004 and February 2007 were included. DALK was performed by Anwar's big bubble technique. Data collected for analysis included preoperative characteristics, intraoperative complications and postoperative acuity, complications and subsequent operations. Results Mean best corrected distance visual acuity (LogMAR) improved from 1.51±0.90 preoperatively to 0.82±0.85 at the last follow-up (p=0.05). 27% of patients with more than 4 years follow-up had a best corrected distance visual acuity of 6/12 or better and 64% were 6/24 or better. Six patients (33%) experienced a recurrence of HSV keratitis and 9 (50%) experienced an episode of graft rejection. There were five cases (28%) of graft failure, four of whom had had a previous episode of graft rejection. Logistic regression did not find an association with graft rejection, HSV recurrence, any other observed postoperative host corneal vascularisation and any postoperative complication. The majority of patients underwent a second operation with 50% requiring cataract surgery. Conclusions DALK for the treatment of HSV related corneal scarring is associated with a high percentage of postoperative complications. DALK in this context is also associated with a large percentage of secondary operations. Patients should be aware of this when giving informed consent for DALK to treat HSV related corneal scars.
Optogenetic strategies to restore vision in patients blind from end-stage retinal degenerations aim to render remaining retinal neurons light-sensitive. We present an innovative combination of multi-electrode array recordings together with a complex pattern-generating light source as a toolset to determine the extent to which neural retinal responses to complex light stimuli can be restored following viral delivery of red-shifted channelrhodopsin in the retinally degenerated mouse. Our data indicate that retinal output level spatiotemporal response characteristics achieved by optogenetic gene therapy closely parallel those observed for normal mice but equally reveal important limitations, some of which could be mitigated using bipolar-cell targeted gene-delivery approaches. As clinical trials are commencing, these data provide important new information on the capacity and limitations of channelrhodopsin-based gene therapies. The toolset we established enables comparing optogenetic constructs and stem-cell-based techniques, thereby providing an efficient and sensitive starting point to identify future approaches for vision restoration.
Inherited optic neuropathies, including Leber Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), are monogenetic diseases with a final common pathway of mitochondrial dysfunction leading to retinal ganglion cell (RGC) death and ultimately loss of vision. They are, therefore, excellent models with which to investigate this ubiquitous disease process—implicated in both common polygenetic ocular diseases (e.g., Glaucoma) and late-onset central nervous system neurodegenerative diseases (e.g., Parkinson disease). In recent years, cellular and animal models of LHON and DOA have matured in parallel with techniques (such as RNA-seq) to determine and analyze the transcriptomes of affected cells. This confluence leaves us at a particularly exciting time with the potential for the identification of novel pathogenic players and therapeutic targets. Here, we present a discussion of the importance of inherited optic neuropathies and how transcriptomic techniques can be exploited in the development of novel mutation-independent, neuroprotective therapies.
Acute intermittent porphyria (AIP) is an inherited deficiency in the haem biosynthesis pathway. AIP is rare, affecting around 1 in 75 000 people. Acute attacks are characterised by abdominal pain associated with autonomic, neurological and psychiatric symptoms. AIP is rarely associated with posterior reversible encephalopathy syndrome (PRES). PRES is a clinicoradiological condition caused by the failure of the posterior circulation to autoregulate, resulting in cerebral oedema, headaches, nausea and seizures. This association is important because drugs used in the management of seizures may worsen an attack of AIP. This article describes a case of AIP and PRES in a young woman.