The effect on visual function of Hydroview intraocular lens opacification: a cross-sectional study.

PURPOSE: Hydroview intraocular lenses (IOLs) have been associated with symptomatic opacification of the optic necessitating IOL exchange. Glare and misty vision have been noted as common presenting symptoms. This study's purpose was to investigate the impact of IOL opacification on objective measurements of visual function, including glare, and on vision-related quality of life. METHODS: All patients who underwent Hydroview IOL implantation at Bristol Eye Hospital between December 2000 and the end of February 2001 were invited for assessment along with patients found to have Hydroview IOL opacification in routine ophthalmic clinics. Glare, visual acuity, contrast sensitivity, visual field, and colour vision were assessed. Vision-related quality of life and subject's symptoms were determined by questionnaire. IOL opacification was assessed by slit lamp bio-microscopy and anterior segment photography. RESULTS: Data from 129 patients were analysed. Fifty subjects had opacified IOLs and 79 clear IOLs. Subjects with opacified IOLs showed dramatically higher levels of glare (adjusted mean difference of 0.63 log units 95% CI, 0.45-0.82; P<0.001) with only mildly reduced visual acuity (adjusted mean difference of 0.09 logMAR units 95% CI, 0.03-0.15; P=0.002). Opacification was associated with poorer contrast sensitivity (P<0.001), visual field (P<0.001), and with lower vision-related quality of life (P<0.001). CONCLUSIONS: This study highlights the significant impact IOL opacification has on visual performance and experience, in particular glare and consequent impact on quality of life. The study shows that to quantify accurately the effect of IOL opacification on vision glare must be assessed.

Reduced mortality compared with national averages following phacoemulsification cataract surgery: a retrospective observational study.

BACKGROUND: Higher or equal rates of mortality are associated with cataract surgery compared with the general population. Cataract surgery has advanced, and the clinical characteristics of the patient undergoing cataract surgery have changed. AIMS: To reinvestigate survival following cataract surgery. METHOD: Survival data were gathered up to the end of 2006 on 933 consecutive patients who underwent cataract surgery between December 2000 and February 2001. These data were compared with national and regional mortality figures, and standardised mortality ratios (SMR) were calculated. RESULTS: After adjusting for age and sex, there was a statistically significant reduced mortality compared with national (SMR = 0.88 (95% CI 0.79 to 0.99)) and regional figures (SMR = 0.87 (95% CI 0.78 to 0.98)). CONCLUSION: All previous studies found decreased survival among cataract surgery cohorts. These data differ from data at earlier times, as cataract surgery seems to be associated with increased survival. This illustrates the need for continual re-evaluation of accepted medical knowledge in the light of changes in practice and population demographics.

Vitreoretinal surgery for retinal detachment in retinochoroidal colobomata.

PURPOSE: To report the management and outcome of retinal reattachment surgery in retinochoroidal coloboma. METHODS: Four patients with retinochoroidal colobomata presented to the Bristol Eye Hospital (a UK tertiary referral center for vitreoretinal surgery) with retinal detachment. INTERVENTION: All were type II colobomatous detachments (three patients with type IIB, one patient with type IID). All eyes underwent vitrectomy with endolaser and/or cryotherapy and three eyes underwent scleral buckling. Two eyes had internal tamponade with gas (SF6, C3F8) while the other two had silicone oil. Endolaser was applied over healthy retinal pigment epithelium. RESULTS: At last follow-up, all (100%) remained attached, with no recurrences. Three patients achieved visual acuity of 6/120 or better and were able to perform satisfactory near work with appropriate magnifiers. The last patient began with hand movement vision and retained similar vision but subjectively felt more navigational. CONCLUSIONS: Good anatomic and functional outcomes can be achieved in this patient group with combined vitrectomy with or without scleral buckling surgery. Endolaser retinopexy is effective over healthy RPE at the margin of the coloboma combined with either gas or oil internal tamponade.

The aetiology of paediatric rhegmatogenous retinal detachment: 15 years experience.

PURPOSE: To provide contemporary data on the aetiology of paediatric rhegmatogenous retinal detachment (RRD) in the UK population. METHODS: Retrospective case series. RESULTS: Eighty-eight eyes in 82 patients (aged 0-16 years) were treated for RRD at Bristol Eye Hospital between 1 January 1990 and 31 December 2004. Seventy-three per cent of patients were male and the main predisposing factors were trauma (53%), associated conditions (27%), and high myopia (17%). Nineteen per cent of RRDs were idiopathic, and the majority of these were due to infero-temporal dialyses. The macula was detached on presentation in 66% of eyes. CONCLUSIONS: The principal causes of paediatric RRDs have not changed over the past 40 years. Those due to congenital cataracts, retinopathy of prematurity, uveitis, and glaucoma are now less prevalent, presumably reflecting advances in their management. Differences with other contemporary series may arise from geographical variation in the prevalence of myopia and other associated conditions, as well as institutional referral patterns. Full examination of the retinal periphery is advised for children with eye injuries (to exclude dialyses).

Emulsification of Densiron-68 used in inferior retinal detachment surgery.

PURPOSE: To report the clinical features of eight patients presenting with emulsification of the heavier than water vitreous substitute, Densiron-68. METHODS: Two patients underwent primary inferior retinal detachment (RD) surgery, two patients underwent giant retinal tear repair, three patients had repair of inferior RD complicated by proliferative vitreoretinopathy and one patient had inferior RD surgery following repair of a scleral rupture. All patients had insertion of Densiron-68. RESULTS: Significant emulsification of Densiron-68 was seen within 12 weeks of surgery in eight cases out of a total of 40 patients receiving Densiron-68. CONCLUSION: Despite adequate Densiron fills, emulsification necessitated its removal. Emulsified Densiron may have contributed to significant intraocular inflammation, epiretinal membrane formation and cystoid macular oedema. Without removal, prolonged presence of emulsified Densiron may lead to keratopathy, secondary glaucoma and retinal toxicity secondary to partitioning of perfluorohexyloctane. This has potentially significant implications on the indications for Densiron-68 use and warrants consideration before deciding on the optimal surgical intervention for inferior RDs.

Cytopathological analysis of vitreous in intraocular lymphoma.

OBJECTIVE: To describe the cytopathological method used in the analysis of vitreous samples in the diagnosis of primary intraocular lymphoma (PIOL). PARTICIPANTS: Seven patients with refractory posterior uveitis referred to a regional ocular inflammatory service were diagnosed as having PIOL between 1999 and 2006. METHODS: Clinical features of the uveitis and cytopathological preparation of the samples were described. All patients underwent vitrectomy and samples were placed in formal saline or prepared fresh. Following paraffin embedding generating a cell block, immunostaining, and polymerase chain reactions were performed. RESULTS: Five women (71.4%) and two men (28.6%) (mean age 67.7 years) were included. Five patients had diagnostic vitrectomy performed within 6 months of presentation, but in two patients diagnosis was delayed up to 2 years. Uveitis was bilateral in two patients. Cytologic and immunohistochemical staining prepared from the vitreous specimens showed PIOL in all patients, and PCR displayed single band of immunoglobulin heavy chain rearrangement in five out of six samples tested. CONCLUSIONS: Diagnosis of PIOL is difficult due to small volume of sample with low number of malignant cells and inadequate preparation of samples. Our method of analysis with fresh samples together with immunohistochemistry and PCR analysis demonstrates a high yield of diagnosis reducing diagnostic delay.

Signal intensity, clinical activity and cross-sectional areas on MRI scans in thyroid eye disease.

The signal intensity from inflamed extra-ocular muscles on short tau inversion recovery (STIR)-sequence magnetic resonance imaging (MRI) is known to correlate with clinical scores of thyroid eye disease (TED) severity. Twenty-one patients who had undergone repeated MRI scanning for TED were studied retrospectively. Signal intensity of extra-ocular muscles (from STIR-sequence MRI) and cross-sectional area (from STIR and T1 MRI) were correlated with Mourits' clinical activity score (CAS). The area of highest signal intensity within the most inflamed extra-ocular muscle, and the average cross-sectional signal intensity of the most inflamed extra-ocular muscle reliably correlated with CAS, and this was maintained as disease activity changed over time. In contrast, isolated measures of muscle cross-sectional area did not correlate with CAS. The extra-ocular muscle cross-sectional area calculated from STIR-sequence MR images was greater than that measured on T1 images. This suggests that muscle area from STIR-sequence MRI may also detect peri-muscular inflammation. We conclude that the peak signal intensity from the most inflamed extra-ocular muscle remains the most reliable correlate of clinical disease activity obtained from these images. STIR-sequence MRI scans provide a number of useful measures of disease activity in TED.

Neural progenitor cells from postmortem adult human retina.

BACKGROUND: Given the presence of neural progenitor cells (NPC) in the retina of other species capable of differentiating into multiple neural components, the authors report the presence of NPC in the adult human retina. A resident population of NPC suggests that the retina may constitutively replace neurons, photoreceptors, and glia. METHODS: Adult human postmortem retinal explants and cell suspensions were used to generate cells in tissue culture that display the features of NPC. The phenotype of cells and differentiation into neurons was determined by immunocytochemistry. Dividing cells were labelled with 5-bromo-2-deoxyuridine (BrdU) and neurospheres were generated and passaged. RESULTS: Cells labelled with nestin, neurofilament M (NFM), rhodopsin, or glial fibrillary acidic protein (GFAP) grew out from explant cultures. BrdU labelling of these cells occurred only with basic fibroblast growth factor (FGF-2). Dissociated retina and pars plana generated primary neurospheres. From primary neurospheres, NPC were passaged to generate secondary neurospheres, neurons, photoreceptors, and glia. BrdU labelling identified dividing cells from neurospheres that differentiated to express NFM and rhodopsin. CONCLUSION: The adult human retina contains NPC and may have the potential to replace neurons and photoreceptors. This has implications for the pathogenesis and treatment of retinal disorders and degenerations, including glaucoma, and those disorders associated with retinal scarring.

Nestin positive cells in adult human retina and in epiretinal membranes.

BACKGROUND/AIM: Nestin is an intermediate filament marker for neural progenitor cells. The authors aimed to identify nestin positive cells in adult human retina and within surgically removed epiretinal membranes. METHODS: Adult human retina and epiretinal membranes were studied. Tissue was fixed and processed for semithin sections or whole mount preparations for immunohistochemical detection of nestin and glial fibrillary acidic protein (GFAP) expression. RESULTS: Nestin positive cells are most prominent at the ora serrata, possess fibrillary processes, small amounts of perinuclear cytoplasm, and are arranged radially within or superficially on the retina. In the posterior retina, speckled cytoplasmic nestin staining is seen around the nuclei of neurons. In the peripapillary retina most of the cells in the retinal ganglion cell layer are nestin positive. These cells appear to represent nestin positive neurons. Speckled cells are also seen in the myelinated portion of the optic nerve. In epiretinal membranes patches of elongated nestin positive cells were found. These cells were also positive for GFAP. CONCLUSIONS: Some neurons and glia in the adult human retina are nestin positive. Their pattern in anterior retina suggests an analogy with the ciliary marginal zone found in many other species. The role of these cells in pathological responses to retinal disease is suggested by the presence of large numbers of ectopic nestin positive cells in epiretinal membranes. The authors hypothesise that nestin positive cells represent a population of progenitor cells from normal adult human retina that differentiate to make up retinal scar tissue.

Novel corneal features in two males with incontinentia pigmenti.

Incontinentia pigmenti (IP) is a rare X linked genetic disorder, which predominantly affects females. The mutations are usually lethal in males. Two male cases are presented; a genetic mosaic for the common IP deletion and another in whom the genetic abnormality has not yet been characterised. Emphasis is placed on the ocular features present in this disorder and in particular a novel corneal feature and its possible aetiology.

Effects of Hot shot on recovery after hypothermic ischemia in neonatal lamb heart.

BACKGROUND: Terminal warm blood cardioplegia, "Hot shot", is the method for providing an energy replenishment and/or early recovery of aerobic metabolism without electromechanical activity at initial reperfusion. The mechanism of beneficial effects of this Hot Shot is multifactorial. This study was designed to assess the effects of terminal warm blood cardioplegia by comparing with oxygenated terminal warm crystalloid cardioplegia. METHODS: In Group HS-B, n=8 (oxygenated blood; 37 degrees C, Ht: 20%, K+ 20 mEq/l, pH 7.237, PO2 219 mmHg) and in Group HS-C, n=8 (bloodless oxygenated (5% CO2+95%O2) crystalloid, 37 degrees C, K+ 20 mEq/l, pH 7.435, PO2 624 mmHg), terminal warm cardioplegia (20 ml/kg for 5 minutes) was studied in the isolated blood perfused neonatal lamb heart following 2 hr of cardioplegic ischemia. Another eight hearts served as control without any kind of terminal cardioplegia. After 60 min of reperfusion, LV function was measured. Coronary blood flow (CBF), oxygen content, and oxygen consumption (MVO2) were measured and the oxygen extraction ratio was calculated in Group HS-B and HS-C during terminal cardioplegia and/or reperfusion. Results are given as % recovery of preischemic values. RESULTS: HS-B as well as HS-C groups showed better functional recovery in maximum developed pressure (DP: 78.0+/-8.3 in HS-B vs 65.2+/-9.2%; p=0.018), maximum dp/dt (67.3+/-6.2 in HS-B, 65.3+/-7.4 in HS-C vs 55.8+/-5.0%; p=0.003, p=0.02), DP V10 (87.1+/-8.5 in HS-B vs 67.2+/-9.9%; p=0.0001), and peak dp/dt V10 (76.4+/-7.6 in HS-B, 69.8+/-8.1 in HS-C vs 58.6+/-6.9 %; p=0.0001) than the control group. Between the HS-B and HS-C groups, HS-B showed better functional recovery in terms of DP V10 (p=0.01). Oxygen delivery of terminal cardioplegia was almost four times higher in HS-B group (90.4+/-17.7 vs 18.7+/-1.1 mcl/ml), contrarily, HS-C group showed four times higher oxygen extraction ratio compared to HS-B group (0.78+/-0.06 vs 0.18+/-0.11), thus oxygen consumption during hot shot was maintained at the same level in both groups. CBF in the control group was lower than that in the other groups at 60 min of reperfusion. CONCLUSIONS: Reperfusion with both terminal warm cardioplegia including blood and oxygenated crystalloid cardioplegia resulted in better recovery of function and higher levels of CBF with slightly better function in terminal warm blood cardioplegia.

Characterization and quantitation of phospholamban and its phosphorylation state using antibodies.

Quantitative immunoassays to discriminate and quantitate phospholamban and its phosphorylation states in heart homogenates were developed using known amounts of protein determined by amino acid analysis. Synthetic 1-52 phospholamban, the hydrophilic 1-25 peptide, and 1-25 phosphopeptides containing P-Ser(16), P-Thr(17), and dually phosphorylated (P-Ser(16), P-Thr(17)) were used to calibrate immunoblot systems. In addition, synthetic 1-52 peptide was phosphorylated using cAMP-dependent protein kinase (P-Ser(16)) or Ca(2+)-calmodulin protein kinase (P-Thr(17)) and then separated from unphosphorylated 1-52 by HPLC prior to quantitation. Further, canine cardiac sarcoplasmic reticulum was phosphorylated in vitro using [gamma-(32)P]-ATP with cAMP-dependent protein kinase and/or Ca(2+)-calmodulin-dependent protein kinase as well as sequential phosphorylation in both orders to assess the veracity of antibody recognition of phosphorylated forms. Western blots proved useful in characterizing the reactivity of the different antibodies to phospholamban and phosphorylated phospholamban, but were inefficient for accurate quantitation and problems with antibody recognition of dually phosphorylated phospholamban were found. mAb 1D11 recognized all forms of phospholamban, polyclonal antibodies 285 and PS-16 were highly selective for P-Ser(16) phospholamban but had diminished reactivity to diphosphorylated (P-Ser(16), P-Thr(17)) phospholamban, and polyclonal antibody PT-17, although selective for P-Thr(17) phospholamban, generated very weak signals on Western blots and reacted poorly with diphosphorylated phospholamban. Results in quantitative immunodot blot experiments were even more compelling. None of the phosphorylation specific antibodies reacted with the diphospho 1-25 phospholamban peptide. Transgenic mouse hearts expressing varying levels of PLB and ferret heart biopsy samples taken before and after isoproterenol perfusion were analyzed. In all samples containing phospholamban, a basal level of Ser(16) phosphorylation (about 4% of the total PLB population) and a lesser amount of Thr(17) phosphorylation was observed. Upon isoproterenol perfusion, Ser(16) phosphorylation increased only to 17% of the total phospholamban population with a similar change in Thr(17) phosphorylation. This suggests that phospholamban phosphorylation may serve as an electrostatic switch that dissociates inactive calcium pump complexes into catalytically active units. Thus, direct correlations between phospholamban phosphorylation state and contractile parameters may not be valid.

Structural studies on phospholamban and implications for regulation of the Ca(2+)-ATPase.

The cardiac sarcoplasmic reticulum (SR) protein phospholamban (PLB) is an endogenous inhibitor of the SR Ca(2+)-ATPase. Phosphorylation of PLB relieves this inhibition and up-regulates calcium transport. PLB has proved remarkably difficult to study by conventional solution-state nuclear magnetic resonance (NMR) methods, due primarily to the extreme hydrophobic nature of the protein and its propensity to form pentamers. That the C-terminal domain of PLB is helical and membrane spanning is now well established; the structure of the cytoplasmic domain is relatively ill defined. In order to discern the effect of phosphorylation on the structure of the cytoplasmic domain, we have characterized a variety of model peptides in several structure-inducing and/or lipid-mimicking environments using circular dichroism and solution-state NMR. The resolution of peptide structures obtained in aqueous trifluoroethanol was markedly improved by the incorporation of 15N labels into the peptide backbone, allowing a variety of isotope edited, filtered, and resolved techniques to be applied. Molecular dynamics simulations on the full-length protein were combined with an analysis of published data to suggest a revised model for the structure of PLB.

Ultrabroadband chirped mirrors for femtosecond lasers.

We report on the performance of widely tunable femtosecond and continuous-wave Ti:sapphire lasers that use a newly developed ultrabroadband mirror set. The mirrors exhibit high reflectivity (R > 99%) and smooth variation of group delay versus frequency over a wavelength range from 660 to 1060 nm. Mode-locked operation with pulse durations of 85 fs was achieved from 693 to 978 nm with only one set of ultrabroadband mirrors.