Clinical and cost-effectiveness of internal limiting membrane peeling for patients with idiopathic full thickness macular hole. Protocol for a Randomised Controlled Trial:FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study)

Background: A full-thickness macular hole (FTMH) is a common retinal condition associated with impaired vision. Randomised controlled trials (RCTs) have demonstrated that surgery, by means of pars plana vitrectomy and post-operative intraocular tamponade with gas, is effective for stage 2, 3 and 4 FTMH. Internal limiting membrane (ILM) peeling has been introduced as an additional surgical manoeuvre to increase the success of the surgery; i.e. increase rates of hole closure and visual improvement. However, little robust evidence exists supporting the superiority of ILM peeling compared with no-peeling techniques. The purpose of FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study) is to determine whether ILM peeling improves the visual function, the anatomical closure of FTMH, and the quality of life of patients affected by this disorder, and the cost-effectiveness of the surgery. Methods/Design: Patients with stage 2-3 idiopathic FTMH of less or equal than 18 months duration (based on symptoms reported by the participant) and with a visual acuity = 20/40 in the study eye will be enrolled in this FILMS from eight sites across the UK and Ireland. Participants will be randomised to receive combined cataract surgery (phacoemulsification and intraocular lens implantation) and pars plana vitrectomy with postoperative intraocular tamponade with gas, with or without ILM peeling. The primary outcome is distance visual acuity at 6 months. Secondary outcomes include distance visual acuity at 3 and 24 months, near visual acuity at 3, 6, and 24 months, contrast sensitivity at 6 months, reading speed at 6 months, anatomical closure of the macular hole at each time point (1, 3, 6, and 24 months), health related quality of life (HRQOL) at six months, costs to the health service and the participant, incremental costs per quality adjusted life year (QALY) and adverse events. Discussion: FILMS will provide high quality evidence onthe role of ILM peeling in FTMH surgery. © 2008 Lois et al; licensee BioMed Central Ltd.

Internal limiting membrane peeling versus no peeling for idiopathic full-thickness macular hole: A pragmatic randomized controlled trial

PURPOSE. To determine whether internal limiting membrane (ILM) peeling is effective and cost effective compared with no peeling in patients with idiopathic stage 2 or 3 full-thickness maculay hole (FTMH). METHODS. This was a pragmatic multicenter randomized controlled trial. Eligible participants from nine centers were randomized to ILM peeling or no peeling (1:1 ratio) in addition to phacovitrectomy, including detachment and removal of the posterior hyaloid and gas tamponade. The primary outcome was distance visual acuity (VA) at 6 months after surgery. Secondary outcomes included hole closure, distance VA at other time points, near VA, contrast sensitivity, reading speed, reoperations, complications, resource use, and participant-reported health status, visual function, and costs. RESULTS. Of 141 participants randomized in nine centers, 127 (90%) completed the 6-month follow-up. Nonstatistically significant differences in distance visual acuity at 6 months were found between groups (mean difference, 4.8; 95% confidence interval [CI], -0.3 to 9.8; P = 0.063). There was a significantly higher rate of hole closure in the ILM-peel group (56 [84%] vs. 31 [48%]) at 1 month (odds ratio [OR], 6.23; 95% CI, 2.64-14.73; P <0.001) with fewer reoperations (8 [12%] vs. 31 [48%]) performed by 6 months (OR, 0.14; 95% CI, 0.05- 0.34; P <0.001). Peeling the ILM is likely to be cost effective. CONCLUSIONS. There was no evidence of a difference in distance VA after the ILM peeling and no-ILM peeling techniques. An important benefit in favor of no ILM peeling was ruled out. Given the higher anatomic closure and lower reoperation rates in the ILM-peel group, ILM peeling seems to be the treatment of choice for idiopathic stage 2 to 3 FTMH. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

Cost-effectiveness of internal limiting membrane peeling versus no peeling for patients with an idiopathic full-thickness macular hole:Results from a randomised controlled trial

Aim: To determine whether internal limiting membrane (ILM) peeling is cost-effective compared with no peeling for patients with an idiopathic stage 2 or 3 full-thickness macular hole. Methods: A cost-effectiveness analysis was performed alongside a randomised controlled trial. 141 participants were randomly allocated to receive macular-hole surgery, with either ILM peeling or no peeling. Health-service resource use, costs and quality of life were calculated for each participant. The incremental cost per quality-adjusted life year (QALY) gained was calculated at 6 months. Results: At 6 months, the total costs were on average higher (£424, 95% CI -182 to 1045) in the No Peel arm, primarily owing to the higher reoperation rate in the No Peel arm. The mean additional QALYs from ILM peel at 6 months were 0.002 (95% CI 0.01 to 0.013), adjusting for baseline EQ-5D and other minimisation factors. A mean incremental cost per QALY was not computed, as Peeling was on average less costly and slightly more effective. A stochastic analysis suggested that there was more than a 90% probability that Peeling would be cost-effective at a willingness-to-pay threshold of £20 000 per QALY. Conclusion: Although there is no evidence of a statistically significant difference in either costs or QALYs between macular hole surgery with or without ILM peeling, the balance of probabilities is that ILM Peeling is likely to be a cost-effective option for the treatment of macular holes. Further long-term follow-up data are needed to confirm these findings.

Internal Limiting Membrane Peeling in Vitreo-retinal Surgery

Peeling the internal limiting membrane of the retina has become a very common procedure performed by vitreo-retinal surgeons. The combination of new microsurgical instrumentation with the availability of different dyes to stain this thin and transparent membrane has facilitated the performance of internal limiting membrane peeling, reducing the time and trauma associated with this maneuver. Internal limiting membrane peeling has been used to treat a variety of retinal pathologies, including full-thickness macular hole, epiretinal membrane, macular edema, vitreomacular traction syndrome, and Terson syndrome, among others. Although it appears that peeling the internal limiting membrane in these retinal conditions may be associated with better anatomical and visual outcomes following surgery, further evidence through randomized controlled clinical trials is still needed to guide the vitreo-retinal surgeon on the appropriate use of this surgical maneuver. © 2008 Elsevier Inc. All rights reserved.

Horizontal Descemet's membrane break due to birth trauma

We report an unusual case of horizontal corneal Descemet's membrane break due to birth trauma. The patient had a difficult birth with trauma to her right eye and poor vision. However unlike the reports in literature, which describe these breaks to have a characteristic vertical or vertically oblique orientation in birth trauma, the breaks in our patient were horizontal. No other cause was found for these Descemet's breaks.

Amniotic membrane transplantation for ocular surface reconstruction

Aims - To evaluate the efficacy of amniotic membrane transplantation (AMT) for ocular surface reconstruction. Methods - 10 consecutive patients who underwent AMT were included. The indications were: group A, cases with persistent epithelial defect after corneal abscess (n = 1), radiation (n = 1), or chemical burn (n = 3); group B, cases with epithelial defect and severe stromal thinning and impending or recent perforation, due to chemical burn (two patients, three eyes) or corneal abscess (n = 2); group C, to promote corneal epithelium healing and prevent scarring after symblepharon surgery with extensive corneo-conjunctival adhesion (n = 1). Under sterile conditions amniotic membrane was prepared from a fresh placenta of a seronegative pregnant woman and stored at -70°C. This technique involved the use of amniotic membrane to cover the entire cornea and perilimbal area in groups A and B, and the epithelial defect only in group C. Results - The cornea healed satisfactorily in four of five patients in group A, but the epithelial defect recurred in one of these patients. After AMT three patients underwent limbal transplantation and one penetrating keratoplasty and cataract extraction. In group B amniotic membrane transplantation was not helpful, and all cases underwent an urgent tectonic corneal graft. Surgery successfully released the symblepharon, promoted epithelialisation and prevented adhesions in the case of group C. Conclusion - AMT was effective to promote corneal healing in patients with persistent epithelial defect, and appeared to be helpful after surgery to release corneo-conjunctival adhesion. Most surgery for further surface rehabilitation. Amniotic membrane used as a patch was not effective to prevent tectonic corneal graft in cases with severe stromal thinning and impending or recent perforation.

Profiling the ionome of rice and its use in discriminating geographical origins at the regional scale, China

Element profile was investigated for their use to trace the geographical origin of rice (Oryza sativa L.) samples. The concentrations of 13 elements (calcium (Ca), potassium (K), magnesium (Mg), phosphorus (P), boron (B), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), arsenic (As), selenium (Se), molybdenum (Mo), and cadmium (Cd)) were determined in the rice samples by inductively coupled plasma optical emission and mass spectrometry. Most of the essential elements for human health in rice were within normal ranges except for Mo and Se. Mo concentrations were twice as high as those in rice from Vietnam and Spain. Meanwhile, Se concentrations were three times lower in the whole province compared to the Chinese average level of 0.088 mg/kg. About 12% of the rice samples failed the Chinese national food safety standard of 0.2 mg/kg for Cd. Combined with the multi-elemental profile in rice, the principal component analysis (PCA), discriminant function analysis (DFA) and Fibonacci index analysis (FIA) were applied to discriminate geographical origins of the samples. Results indicated that the FIA method could achieve a more effective geographical origin classification compared with PCA and DFA, due to its efficiency in making the grouping even when the elemental variability was so high that PCA and DFA showed little discriminatory power. Furthermore, some elements were identified as the most powerful indicators of geographical origin: Ca, Ni, Fe and Cd. This suggests that the newly established methodology of FIA based on the ionome profile can be applied to determine the geographical origin of rice.

A Superfamily of Actin-Binding Proteins at the Actin-Membrane Nexus of Higher Plants

Complex animals use a wide variety of adaptor proteins to produce specialized sites of interaction between actin and membranes. Plants do not have these protein families, yet actin-membrane interactions within plant cells are critical for the positioning of subcellular compartments, for coordinating intercellular communication, and for membrane deformation [1]. Novel factors are therefore likely to provide interfaces at actin-membrane contacts in plants, but their identity has remained obscure. Here we identify the plantspecific Networked (NET) superfamily of actin-binding proteins, members of which localize to the actin cytoskeleton and specify different membrane compartments. The founding member of the NET superfamily, NET1A, is anchored at the plasma membrane and predominates at cell junctions, the plasmodesmata. NET1A binds directly to actin filaments via a novel actin-binding domain that defines a superfamily of thirteen Arabidopsis proteins divided into four distinct phylogenetic clades. Members of other clades identify interactions at the tonoplast, nuclear membrane, and pollen tube plasma membrane, emphasizing the role of this superfamily in mediating actin-membrane interactions.

Arabidopsis Rab-E GTPases exhibit a novel interaction with a plasma-membrane phosphatidylinositol-4-phosphate 5-kinase

Rab GTPases of the Arabidopsis Rab-E subclass are related to mammalian Rab8 and are implicated in membrane trafficking from the Golgi to the plasma membrane. Using a yeast two-hybrid assay, Arabidopsis phosphatidylinositol-4-phosphate 5-kinase 2 (PtdIns(4)P 5-kinase 2; also known as PIP5K2), was shown to interact with all five members of the Rab-E subclass but not with other Rab subclasses residing at the Golgi or trans-Golgi network. Interactions in yeast and in vitro were strongest with RAB-E1d[Q74L] and weakest with the RAB-E1d[S29N] suggesting that PIP5K2 interacts with the GTP-bound form. PIP5K2 exhibited kinase activity towards phosphatidylinositol phosphates with a free 5-hydroxyl group, consistent with PtdIns(4)P 5-kinase activity and this activity was stimulated by Rab binding. Rab-E proteins interacted with PIP5K2 via its membrane occupancy and recognition nexus (MORN) domain which is missing from animal and fungal PtdIns(4)P 5-kinases. In plant cells, GFP:PIP5K2 accumulated at the plasma membrane and caused YFP:RAB-E1d to relocate there from its usual position at the Golgi. GFP:PIP5K2 was rapidly turned over by proteasomal activity in planta, and overexpression of YFP:PIP5K2 caused pleiotropic growth abnormalities in transgenic Arabidopsis. We propose that plant cells exhibit a novel interaction in which PIP5K2 binds GTP-bound Rab-E proteins, which may stimulate temporally or spatially localized PtdIns(4,5)P(2) production at the plasma membrane.

Effect of membrane stiffness and cytoskeletal element density on mechanical stimuli within cells: an analysis of the consequences of ageing in cells

A finite element model of a single cell was created and used to investigate the effects of ageing on biophysical stimuli generated within a cell. Major cellular components were incorporated in the model: the membrane, cytoplasm, nucleus, microtubules, actin filaments, intermediate filaments, nuclear lamina, and chromatin. The model used multiple sets of tensegrity structures. Viscoelastic properties were assigned to the continuum components. To corroborate the model, a simulation of Atomic Force Microscopy (AFM) indentation was performed and results showed a force/indentation simulation with the range of experimental results.

Ageing was simulated by both increasing membrane stiffness (thereby modelling membrane peroxidation with age) and decreasing density of cytoskeletal elements (thereby modelling reduced actin density with age). Comparing normal and aged cells under indentation predicts that aged cells have a lower membrane area subjected to high strain compared to young cells, but the difference, surprisingly, is very small and would not be measurable experimentally. Ageing is predicted to have more significant effect on strain deep in the nucleus. These results show that computation of biophysical stimuli within cells are achievable with single-cell computational models whose force/displacement behaviour is within experimentally observed ranges. the models suggest only small, though possibly physiologically-significant, differences in internal biophysical stimuli between normal and aged cells.