Incidence, determinants and outcome of chronic kidney disease after adult heart transplantation in the United Kingdom

Background: We investigated the incidence of chronic kidney disease (CKD) in the United Kingdom heart transplant population, identified risk factors for the development of CKD, and assessed the impact of CKD on subsequent survival.

Methods: Data from the UK Cardiothoracic Transplant Audit and UK Renal Registry were linked for 1732 adult heart transplantations, 1996 to 2007. Factors influencing time to CKD, defined as National Kidney Foundation CKD stage 4 or 5 or preemptive kidney transplantation, were identified using a Cox proportional hazards model. The effects of distinct CKD stages on survival were evaluated using time-dependent covariates.

Results: A total of 3% of patients had CKD at transplantation, 11% at 1-year and more than 15% at 6 years posttransplantation and beyond. Earlier transplantations, shorter ischemia times, female, older, hepatitis C virus positive, and diabetic recipients were at increased risk of developing CKD, along with those with impaired renal function pretransplantation or early posttransplantation. Significant differences between transplantation centers were also observed. The risk of death was significantly higher for patients at CKD stage 4, stage 5 (excluding dialysis), or on dialysis, compared with equivalent patients surviving to the same time point with CKD stage 3 or lower (hazard ratios of 1.66, 8.54, and 4.07, respectively).

Conclusions: CKD is a common complication of heart transplantation in the UK, and several risk factors identified in other studies are also relevant in this population. By linking national heart transplantation and renal data, we have determined the impact of CKD stage and dialysis treatment on subsequent survival in heart transplant recipients.

Epigenetics:Time to translate into transplantation

Substantial progress has been made in identifying genetic loci associated with multifactorial disorders, including variants that seem to impact outcomes following solid organ transplantation. Despite these advances, much of the heritability and susceptibility to chronic disease processes remains unexplained. Epigenetic modifications may exert their effect independently or complementary to genetic variants. Epigenetic modifications can change gene expression without altering the DNA sequence. These modifications are dynamic, potentially heritable, and can be induced by environmental stimuli or drugs. The impact of epigenetic phenomena on the outcomes of organ transplantation is currently poorly understood. Epigenetic modifications can occur during periods of illness; these may persist and potentially influence allograft outcomes. Epigenetic mechanisms influence the activation, proliferation, and differentiation of the immune cells involved in allograft rejection. The donor's epigenome may also impact transplant survival, and initial research has demonstrated that peritransplant conditions induce rapid epigenetic modification within the allograft. Further research will help to define the importance of epigenetic modifications in transplantation. This will potentially lead to the identification of useful biomarkers and the development of novel pharmacotherapies. This review explores the nature of epigenetic modification in disease and the emerging evidence for epigenetic influences on allograft survival.

Outcome of pregnancy following renal transplantation

Successful renal transplantation improves fertility with 1 in 50 women of childbearing age becoming pregnant. Pregnancy following renal transplantation is associated with increased maternal and fetal complications. In Belfast 118 women of childbearing age (15-45 yrs) have received a renal allograft and of these 14 (12%) have become pregnant. Twenty-seven pregnancies have resulted in 23 live births (including one set of identical twins), 1 still birth and 4 first trimester abortions. The most frequent complications were hypertension and prematurity. In this group of patients, whose sole immunosuppressive therapy was azathioprine and prednisolone, pregnancy post transplantation was associated with frequent successful outcome and a low incidence of maternal and fetal complications.

A review on the use of corneal implants for the treatment of presbyopia

In recent years there has seen an increased interest in refractive surgery for the correction of presbyopia. This can be attributed to a number of factors such as the increased demand from patients to have perfect vision without the need for glasses, spurred on by the success of high street refractive laser surgery. Also the World Health Organisation (WHO) estimated in 2005 that over a 1.04 billion people worldwide are affected by presbyopia (Holden et al. 2008). This vast number of people is valued as a potential market and is a huge enticement to the ophthalmic industry to try and develop devices and products to treat this condition. Recent advances in technology have renewed interest in the implantation of corneal inlays for surgical treatment of presbyopia. Dexl et al. (2011) suggest that the reason for this is the further development of biomaterial technology, advances in femtosecond laser and the need for a reversible presbyopic treatment.

Diabetic-like loss of corneal sensitivity in the 50% galactose fed rat is ameliorated with topical administration of an aldose reductase inhibitor

Purpose: To investigate the temporal course of corneal sensitivity loss & the role of aldose reductase inhibitors (ARI) in an animal model of diabetic ocular complications. Methods: Weanling male S-D rats were randomly grouped to received ad libitum water & diet consisting of Purina (#5001) w/ either: 50% starch (CON,n=15) or 50% D-galactose (GAL,n=30). Half the galactosemic rats (ARI,n=15) received topical 0.25% CT-112 (3x daily, 20µl, Senju Pharmaceutical Co., Japan). Control & remaining half of the galactosemic animals received equivalent doses of saline eyedrops. Rats were restrained w/o medication during sensitivity measurements conducted w/ a Cochet-Bonnet Aesthesiometer mounted on a micromanipulator. The end of the filament (0.012mm dia.), which applied a mean pressure of 0.96 g/mm perpendicular to the corneal surface at center, was in the plane of focus of a slit-lamp biomicroscope. Measurements were conducted by two investigators which were masked to the treatment group. The average blink-responses from 10 consecutive stimuli to each cornea were expressed as a percent. Results: Mean (±SD) baseline corneal sensitivity in all groups were similar (CON 73%±11, GAL 71%±15, ARI 74%±16). Corneal sensitivity in the galactosemic rat was decreased (p

Transcameral suture to prevent tube-corneal touch after glaucoma drainage device implantation: a new surgical technique

PURPOSE: To report a new technique to correct tube position in anterior chamber after glaucoma drainage device implantation.

PATIENT AND METHODS: A patient who underwent a glaucoma drainage device implantation was noted to have the tube touching the corneal endothelium. A 10/0 polypropylene suture with double-armed 3-inch long straight needle was placed transcamerally from limbus to limbus, in the superior part of the eye, passing the needle in front of the tube.

RESULTS: The position of the tube in the anterior chamber was corrected with optimal distance from corneal endothelium and iris surface. The position remained satisfactory after 20 months of follow-up.

CONCLUSIONS: The placement of a transcameral suture offers a safe, quick, and minimal invasive intervention for the correction of the position of a glaucoma drainage device tube in the anterior chamber.

Surveillance of severe chemical corneal injuries in the UK

AIM: To estimate the incidence of severe chemical corneal injuries in the UK and describe presenting clinical features and initial management.

METHODS: All patients with severe chemical corneal injury in the UK from December 2005 to November 2006 inclusive were prospectively identified using the British Ophthalmological Surveillance Unit. Reporting ophthalmologists provided information regarding presentation and follow-up.

RESULTS: Twelve cases were identified, giving a minimum estimated incidence in the UK of severe chemical corneal injury of 0.02 per 100,000. 66.7% of injuries were in males of working age, 50% occurred at work, and alkali was causative in 66.7%. Only one patient was wearing eye protection at the time of injury, 75% received immediate irrigation. Six patients required one or more surgical procedures, most commonly amniotic membrane graft. At 6 months' follow-up, the best-corrected visual acuity was 6/12 or better in five patients, and worse than 6/60 in two.

CONCLUSION: The incidence of severe chemical corneal injury in the UK is low. The cases that occur can require extended hospital treatment, with substantial ocular morbidity and visual sequelae. Current enforcement of eye protection in the workplace in the UK has probably contributed to a reduced incidence of severe ocular burns.

Corneal biomechanical properties in primary open angle glaucoma and normal tension glaucoma

PURPOSE: To determine and compare the corneal biomechanical properties between eyes with primary open angle glaucoma (POAG) and eyes with normal tension glaucoma (NTG). PATIENTS AND METHODS: Prospective cross-sectional study. Consecutive eligible POAG and NTG patients attending the Glaucoma Clinic had assessment of their corneal biomechanical properties-corneal hysteresis (CH) and corneal resistance factor (CRF)-using the Ocular Response Analyzer by an observer masked to the diagnosis. Exclusion criteria included previous intraocular surgery, corneal pathology, inflammatory connective tissue disease, and refraction of 5-dimensional or over. If both eyes were eligible, then the right eye was used for analysis. The main outcome measures were corneal hysteresis and CRF measurements. Data analysis was performed using the t test and general linear model. RESULTS: Eighty-one patients (80 whites) were analyzed. Forty had NTG, whereas 41 had POAG. Thirty-five were females. There was a statistically significant difference in mean CH (NTG 9.6±1.3 mm Hg; POAG 9.0±1.4 mm Hg; P=0.01), but not in mean CRF (NTG 9.9±1.4; POAG 10.8±1.7; P=0.06). The highest recorded Goldmann applanation intraocular pressure (IOP) was statistically significantly associated with lower CH (P=0.01) and higher CRF (P=0.02). CONCLUSIONS: There was a small but statistically significant difference in the mean CH between POAG and NTG (CH was higher in NTG). The highest recorded Goldmann applanation IOP was also statistically significantly correlated with lower CH and higher CRF, suggesting that alterations to the corneal biomechanical properties may occur as a result of chronic raised IOP in POAG. © 2008 by Lippincott Williams & Wilkins.

Lower corneal hysteresis in glaucoma patients with acquired pit of the optic nerve (APON)

Objective: Acquired pit-like changes of the optic nerve head (APON) are characteristic of glaucomatous damage and may be a sign of a localized susceptibility of the optic nerve. Thus, it is possible that biomechanical properties of the ocular tissues may play a pressure-independent role in the pathogenesis of glaucoma. Corneal hysteresis (CH) appears to provide information of the biomechanical properties of the ocular hull tissues. The purpose of this study was to compare CH of patients with primary open angle glaucoma (POAG) with and without APON. Methods: A prospective case control study was done. POAG patients with and without APON were measured using the Ocular Response Analyzer by masked investigators. Patients in both groups were matched for sex, age, corneal thickness, and type of glaucoma according to maximal IOP (NTG or POAG). Statistical analysis was done using ANOVA. Results: Corneal hysteresis of 16 glaucomatous eyes with APON and 32 controls (glaucoma without APON) was measured. The mean (±SD) CH in the APON group was 8.89 (±1.53) and 10.2 (±1.05) in the control group. The difference is statistically significant (p = 0.005). Conclusions: Corneal hysteresis in POAG patients with APON was significantly lower than in patients that did not have such structural changes of the optic disc. These findings may reflect pressure-independent mechanisms involved in the pathogenesis of such glaucomatous optic nerve changes. © Springer-Verlag 2007.

Evaluation of corneal endothelium and keratic precipitates by specular microscopy in anterior uveitis

Background - The study of corneal endothelium, by specular microscopy, in patients with anterior uveitis has largely been restricted to observations on the endothelial cells. In this prospective study 'keratic precipitates' (KP) in different types of uveitis were examined in different stages of the disease process and the endothelial changes occurring in the vicinity of the KP were evaluated in comparison with the endothelium of the uninvolved eye. Methods - 13 patients with active unilateral uveitis were recruited. The mean age was 42.9 years (range 20-76 years). A Tomey-1100 contact wide field specular (x10) microscope was used to capture endothelial images and KP until the resolution of uveitis. Data regarding type of uveitis, number, size, and nature of KP were recorded. Automated morphometric analysis was done for cell size, cell density and coefficient of variation, and statistical comparisons of cell size and cell density were made (Student's t test) between the endothelium in the vicinity of fresh and resolving KP, fresh KP and normal endothelium, and resolving KP and normal endothelium. Results - On specular microscopy, fresh KP were seen as dense, white glistening deposits occupying 5-10 endothelial cells in diameter and fine KP were widely distributed and were one or two endothelial cells in diameter. The KP in Posner-Schlossman syndrome had a distinct and different morphology. With clinical remission of uveitis, the KP were observed to undergo characteristic morphological changes and old KP demonstrated a large, dark halo surrounding a central white deposit and occasionally a dark shadow or a 'lacuna' replaced the site of the original KP. Endothelial blebs were noted as dark shadows or defects in the endothelial mosaic in patients with recurrent uveitis. There was significant statistical difference in the mean cell size and cell density of endothelial cells in the vicinity of fresh KP compared with normal endothelium of the opposite eye. Conclusion - This study elucidated the different specular microscopic features of KP in anterior uveitis. Distinct morphological features of large and fine KP were noted. These features underwent dramatic changes on resolution of uveitis. The endothelium was abnormal in the vicinity of KP, which returned to near normal values on resolution of uveitis.