CD133+ adult human retinal cells remain undifferentiated in Leukaemia Inhibitory Factor (LIF)

<p>Abstract</p> <p>Background</p> <p>CD133 is a cell surface marker of haematopoietic stem and progenitor cells. Leukaemia inhibitory factor (LIF), sustains proliferation and not differentiation of embryonic stem cells. We used CD133 to purify adult human retinal cells and aimed to determine what effect LIF had on these cultures and whether they still had the ability to generate neurospheres.</p> <p>Methods</p> <p>Retinal cell suspensions were derived from adult human post-mortem tissue with ethical approval. With magnetic automated cell sorting (MACS) CD133⁺retinal cells were enriched from post mortem adult human retina. CD133⁺retinal cell phenotype was analysed by flow cytometry and cultured cells were observed for proliferative capacity, neuropshere generation and differentiation with or without LIF supplementation.</p> <p>Results</p> <p>We demonstrated purification (to 95%) of CD133⁺cells from adult human postmortem retina. Proliferating cells were identified through BrdU incorporation and expression of the proliferation markers Ki67 and Cyclin D1. CD133⁺retinal cells differentiated whilst forming neurospheres containing appropriate lineage markers including glia, neurons and photoreceptors. LIF maintained CD133⁺retinal cells in a proliferative and relatively undifferentiated state (Ki67, Cyclin D1 expression) without significant neurosphere generation. Differentiation whilst forming neurospheres was re-established on LIF withdrawal.</p> <p>Conclusion</p> <p>These data support the evidence that CD133 expression characterises a population of cells within the resident adult human retina which have progenitor cell properties and that their turnover and differentiation is influenced by LIF. This may explain differences in retinal responses observed following disease or injury.</p

Recovery from macular phototoxicity after corneal triple procedure

PURPOSE: Visual recovery from macular phototoxicity in 2 cases after prolonged exposure to operating microscope light from uncomplicated corneal triple-procedure surgery. Recovery is discussed in the context of repair and regeneration. METHODS: Retrospective case reports. RESULTS: Immediately postoperatively, both patients reported positive scotomata and were found to have macular retinal pigment epithelial depigmentation. In 1 case, the fovea was involved. By 6 to 12 months, the scotomata had disappeared despite large areas of retinal pigment epithelial hyperpigmentation remaining. CONCLUSION: Recovery from macular phototoxicity occurs, although the mechanism remains unclear. Positive scotomata in these cases resolved over several months. The time scale of recovery was consistent with the time required for cellular replacement and possible differentiation from neural progenitor cells

The cataract national data set electronic multi-centre audit of 55,567 operations: case-mix adjusted surgeon's outcomes for posterior capsule rupture.

AIMS: To develop a methodology for case-mix adjustment of surgical outcomes for individual cataract surgeons using electronically collected multi-centre data conforming to the cataract national data set (CND). METHODS: Routinely collected anonymised data were remotely extracted from electronic patient record (EPR) systems in 12 participating NHS Trusts undertaking cataract surgery. Following data checks and cleaning, analyses were carried out to risk adjust outcomes for posterior capsule rupture rates for individual surgeons, with stratification by surgical grade. RESULTS: A total of 406 surgeons from 12 NHS Trusts submitted data on 55,567 cataract operations between November 2001 and July 2006 (86% from January 2004). In all, 283 surgeons contributed data on >25 cases, providing 54,319 operations suitable for detailed analysis. Case-mix adjusted results of individual surgeons are presented as funnel plots for all surgeons together, and separately for three different grades of surgeon. Plots include 95 and 99.8% confidence limits around the case-mix adjusted outcomes for detection of surgical outliers. CONCLUSIONS: Routinely collected electronic data conforming to the CND provides sufficient detail for case-mix adjustment of cataract surgical outcomes. The validation of these risk indicators should be carried out using fresh data to confirm the validity of the risk model. Once validated this model should provide an equitable approach for peer-to-peer comparisons in the context of revalidation

The Cataract National Dataset electronic multi-centre audit of 55,567 operations: risk indicators for monocular visual acuity outcomes.

AIMS: To report risk factors for visual acuity (VA) improvement and harm following cataract surgery using electronically collected multi-centre data conforming to the Cataract National Dataset (CND). METHODS: Routinely collected anonymised data were remotely extracted from the electronic patient record systems of 12 participating NHS Trusts undertaking cataract surgery. Following data checks and cleaning, analyses were performed to identify risk indicators for: (1) a good acuity outcome (VA 6/12 or better), (2) the pre- to postoperative change in VA, and (3) VA loss (doubling or worse of the visual angle). RESULTS: In all, 406 surgeons from 12 NHS Trusts submitted data on 55,567 cataract operations. Preoperative VA was known for 55,528 (99.9%) and postoperative VA outcome for 40,758 (73.3%) operations. Important adverse preoperative risk indicators found in at least 2 of the 3 analyses included older age (3), short axial length (3), any ocular comorbidity (3), age-related macular degeneration (2), diabetic retinopathy (3), amblyopia (2), corneal pathology (2), previous vitrectomy (2), and posterior capsule rupture (PCR) during surgery (3). PCR was the only potentially modifiable adverse risk indicator and was powerfully associated with VA loss (OR=5.74). CONCLUSION: Routinely collected electronic data conforming to the CND provide sufficient detail for identification and quantification of preoperative risk indicators for VA outcomes of cataract surgery. The majority of risk indicators are intrinsic to the patient or their eye, with a notable exception being PCR during surgery

United Kingdom national ophthalmology database study: Diabetic retinopathy; report 1: Prevalence of centre-involving diabetic macular oedema and other grades of maculopathy and retinopathy in hospital eye services

AimsTo report estimates of the prevalence of diabetic retinopathy (DR) and maculopathy grades for a large cohort of patients managed by the UK hospital eye service (HES).MethodsAnonymised data were extracted from 30 UK NHS hospital trusts using a single ophthalmic electronic medical record (EMR) for the period from April 2000 to November 2010 to create the National Ophthalmology Database (NOD). From 2007, the EMR facilitated capture of a nationally agreed-upon standardised data set (DR Structured Assessment) relating to the presence or absence of clinical signs of DR and maculopathy. An algorithm in the software automatically calculated the Early Treatment of Diabetic Retinopathy Study grades of retinopathy and maculopathy.ResultsBetween 2007 and 2010, 307 538 patients had data on the NOD, with 76 127 (24.8%) patients having been recorded as having diabetes. The proportion of patients with diabetes who had a structured assessment increased from 50.7% (2007) to 86.8% (2010). In each NHS year, 12.6-20.6% of eyes with structured assessments had no DR; 59.6-67.3% had non-proliferative DR; and 18.3-20.9% had active or regressed proliferative DR. Clinically significant macular oedema was present in 15.8-18.1% of eyes, and in 8.7-10.0% of eyes, this involved the central macula.ConclusionThis study provides contemporary estimates of the prevalence of retinopathy and maculopathy grades in a large cohort of patients with diabetes managed by the UK HES. Centre-involving diabetic macular oedema, potentially amenable to anti-VEGF therapy, is present in the eyes of almost 10% of these patients. This information is useful for clinicians, health-care economists, and commissioners involved in planning and delivering diabetic eye services