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.

Interventions for prevention of giant retinal tear in the fellow eye

Background: A giant retinal tear is a full-thickness retinal break that extends circumferentially around the retina for 90 degrees ormore in the presence of a posteriorly detached vitreous. It causes significant visual morbidity from retinal detachment and proliferative vitreoretinopathy. The fellow eye of patients who have had a spontaneous giant retinal tear has an increased risk of developing a giant retinal tear, a retinal detachment or both. Interventions such as 360-degree encircling scleral buckling, 360-degree cryotherapy and 360-degree laser photocoagulation have been advocated by some ophthalmologists as prophylaxis for the fellow eye against the development of a giant retinal tear and/or a retinal detachment, or to prevent its extension. Objectives: To evaluate the effectiveness of prophylactic 360-degree interventions in the fellow eye of patients with unilateral giant retinal tear to prevent the occurrence of a giant retinal tear and/or a retinal detachment. Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2008, Issue 4), MEDLINE (January 1950 to December 2008), EMBASE (January 1980 to December 2008) and Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2008). In addition, we searched the proceedings of the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) up to 2008 for information about other relevant studies. There were no language or date restrictions in the search for trials. The electronic databases were last searched on 15 December 2008. Selection criteria: Prospective randomised controlled trials (RCTs) comparing one prophylactic treatment for fellow eyes of patients with giant retinal tear against observation (no treatment) or another form of prophylactic treatment. In the absence of RCTs, we planned to discuss case-control studies that met the inclusion criteria but we would not conduct a meta-analysis using these studies. Data collection and analysis: We did not find any studies that met the inclusion criteria for the review and therefore no assessment of methodological quality or meta-analysis could be performed. Main results: No studies met the inclusion criteria for this review. Authors' conclusions: No strong evidence in the literature was found to support or refute prophylactic 360-degree treatments to prevent a giant retinal tear or a retinal detachment in the fellow eye of patients with unilateral giant retinal tears. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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.

Interventions for prevention of giant retinal tear in the fellow eye.

BACKGROUND: A giant retinal tear is a full-thickness retinal break that extends circumferentially around the retina for 90 degrees or more in the presence of a posteriorly detached vitreous. It causes significant visual morbidity from retinal detachment and proliferative vitreoretinopathy. The fellow eye of patients who have had a spontaneous giant retinal tear has an increased risk of developing a giant retinal tear, a retinal detachment or both. Interventions such as 360-degree encircling scleral buckling, 360-degree cryotherapy and 360-degree laser photocoagulation have been advocated by some ophthalmologists as prophylaxis for the fellow eye against the development of a giant retinal tear and/or a retinal detachment, or to prevent its extension. OBJECTIVES: To evaluate the effectiveness of prophylactic 360-degree interventions in the fellow eye of patients with unilateral giant retinal tear to prevent the occurrence of a giant retinal tear and/or a retinal detachment. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2008, Issue 4), MEDLINE (January 1950 to December 2008), EMBASE (January 1980 to December 2008) and Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2008). In addition, we searched the proceedings of the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) up to 2008 for information about other relevant studies. There were no language or date restrictions in the search for trials. The electronic databases were last searched on 15 December 2008. SELECTION CRITERIA: Prospective randomised controlled trials (RCTs) comparing one prophylactic treatment for fellow eyes of patients with giant retinal tear against observation (no treatment) or another form of prophylactic treatment. In the absence of RCTs, we planned to discuss case-control studies that met the inclusion criteria but we would not conduct a meta-analysis using these studies. DATA COLLECTION AND ANALYSIS: We did not find any studies that met the inclusion criteria for the review and therefore no assessment of methodological quality or meta-analysis could be performed. MAIN RESULTS: No studies met the inclusion criteria for this review. AUTHORS' CONCLUSIONS: No strong evidence in the literature was found to support or refute prophylactic 360-degree treatments to prevent a giant retinal tear or a retinal detachment in the fellow eye of patients with unilateral giant retinal tears.

Interventions for prevention of giant retinal tear in the fellow eye.

A giant retinal tear is a full-thickness retinal break that extends circumferentially around the retina for 90 degrees or more in the presence of a posteriorly detached vitreous. It causes significant visual morbidity from retinal detachment and proliferative vitreoretinopathy. The fellow eye of patients who have had a spontaneous giant retinal tear has an increased risk of developing a giant retinal tear, a retinal detachment or both. Interventions such as 360-degree encircling scleral buckling, 360-degree cryotherapy and 360-degree laser photocoagulation have been advocated by some ophthalmologists as prophylaxis for the fellow eye against the development of a giant retinal tear and/or a retinal detachment, or to prevent its extension. To evaluate the effectiveness of prophylactic 360-degree interventions in the fellow eye of patients with unilateral giant retinal tear to prevent the occurrence of a giant retinal tear, a retinal detachment or both. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 11), MEDLINE (January 1950 to December 2011), EMBASE (January 1980 to December 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 6 December 2011. In addition, we searched the proceedings of the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) up to 2008 for information about other relevant studies. Prospective randomised controlled trials (RCTs) comparing one prophylactic treatment for fellow eyes of patients with giant retinal tear against observation (no treatment) or another form of prophylactic treatment. In the absence of RCTs, we planned to discuss case-control studies that met the inclusion criteria but we would not conduct a meta-analysis using these studies. We did not find any studies that met the inclusion criteria for the review and therefore no assessment of methodological quality or meta-analysis could be performed. No studies met the inclusion criteria for this review. No strong evidence in the literature was found to support or refute prophylactic 360-degree treatments to prevent a giant retinal tear or a retinal detachment in the fellow eye of patients with unilateral giant retinal tears.

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.

Pigment epithelium-derived factor mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized low-density lipoprotein

Oxidized and/or glycated low-density lipoprotein (LDL) may mediate capillary injury in diabetic retinopathy. The mechanisms may involve pro-inflammatory and pro-oxidant effects on retinal capillary pericytes. In this study, these effects, and the protective effects of pigment epithelium-derived factor (PEDF), were defined in a primary human pericyte model. Human retinal pericytes were exposed to 100 microg/ml native LDL (N-LDL) or heavily oxidized glycated LDL (HOG-LDL) with or without PEDF at 10-160 nM for 24 h. To assess pro-inflammatory effects, monocyte chemoattractant protein-1 (MCP-1) secretion was measured by ELISA, and nuclear factor-kappaB (NF-kappaB) activation was detected by immunocytochemistry. Oxidative stress was determined by measuring intracellular reactive oxygen species (ROS), peroxynitrite (ONOO(-)) formation, inducible nitric oxide synthase (iNOS) expression, and nitric oxide (NO) production. The results showed that MCP-1 was significantly increased by HOG-LDL, and the effect was attenuated by PEDF in a dose-dependent manner. PEDF also attenuated the HOG-LDL-induced NF-kappaB activation, suggesting that the inhibitory effect of PEDF on MCP-1 was at least partially through the blockade of NF-kappaB activation. Further studies demonstrated that HOG-LDL, but not N-LDL, significantly increased ONOO(-) formation, NO production, and iNOS expression. These changes were also alleviated by PEDF. Moreover, PEDF significantly ameliorated HOG-LDL-induced ROS generation through up-regulation of superoxide dismutase 1 expression. Taken together, these results demonstrate pro-inflammatory and pro-oxidant effects of HOG-LDL on retinal pericytes, which were effectively ameliorated by PEDF. Suppressing MCP-1 production and thus inhibiting macrophage recruitment may represent a new mechanism for the salutary effect of PEDF in diabetic retinopathy and warrants more studies in future.

The combined effects of diabetes and ionising radiation on the rat retina: an ultrastructural study

The combined effect of STZ-diabetes and ionising radiation on the rat retina was investigated. Wistar rats, which had been diabetic for 6 months, were irradiated with a single dose of x-rays (1500 cGy) and the ultrastructural effects evaluated at 4-10 mths post-irradiation. At 4 months post-irradiation, the outer nuclear layer of the retina was greatly reduced in thickness and the photoreceptor outer segments were disorganised and reduced in length. In addition, the nerve fibre layer contained many cytoid bodies and there were many redundant basement membrane tubes throughout the inner retina. By 6 months post-irradiation, the photoreceptor cells were virtually absent, bringing the external limiting membrane into close apposition to the RPE. Throughout large areas of the outer retina, RPE cells were hypertrophic and some had proliferated into the inner retina. In many regions, proliferating retinal capillaries were observed within the RPE layer, and at 8 months post-irradiation, some vessels extended into the inner retina accompanied by RPE cells. At 10 months post-irradiation, the RPE was atrophic and degenerative with retinal glial cells coming into contact with Bruch's membrane. In some areas, the glia which had breached Bruch's membrane had invaded the underlying choroid. Where glial cells contacted the choriocapillaries, the vessels assumed the appearance of retinal vessels with plump endothelia and no fenestrations. This study has described a progressive inner retinal ischemia, with cytoid bodies, capillary non-perfusion and general atrophy of the inner retina intensifying markedly with increasing post-irradiation time.(ABSTRACT TRUNCATED AT 250 WORDS)

Giant retinal tears

A giant retinal tear (GRT) is a full-thickness neurosensory retinal break that extends circumferentially around the retina for three or more clock hours in the presence of a posteriorly detached vitreous. Its incidence in large population-based studies has been estimated as 1.5% of rhegmatogenous retinal detachments, with a significant male preponderance, and bilaterality in 12.8%. Most GRTs are idiopathic, with trauma, hereditary vitreoretinopathies and high myopia each being causative in decreasing frequency. The vast majority of GRTs are currently managed with a pars plana vitrectomy; the use of adjunctive circumferential scleral buckling is debated, but no studies have shown a clear anatomical or visual advantage with its use. Similarly, silicone oil tamponade does not influence long-term outcomes when compared with gas. Primary and final retinal reattachment rates are achieved in 88% and 95% of patients, respectively. Even when the retina remains attached, however, visual recovery may be limited. Furthermore, fellow eyes of patients with a GRT are at higher risk of developing retinal tears and retinal detachment. Prophylactic treatment under these circumstances may be considered but there is no firm evidence of its efficacy at the present time.

Automatic Analysis of Digital Retinal Images for Glaucoma Detection

In this paper we propose a novel automated glaucoma detection framework for mass-screening that operates on inexpensive retinal cameras. The proposed methodology is based on the assumption that discriminative features for glaucoma diagnosis can be extracted from the optical nerve head structures,
such as the cup-to-disc ratio or the neuro-retinal rim variation. After automatically segmenting the cup and optical disc, these features are feed into a machine learning classifier. Experiments were performed using two different datasets and from the obtained results the proposed technique provides
better performance than approaches based on appearance. A main advantage of our approach is that it only requires a few training samples to provide high accuracy over several different glaucoma stages.

Immunohistochemical study of pig retinal development

PURPOSE: The pig eye is similar to the human eye in terms of anatomy, vasculature, and photoreceptor distribution, and therefore provides an attractive animal model for research into retinal disease. The purpose of this study was to characterize retinal histology in the developing and mature pig retina using antibodies to well established retinal cell markers commonly used in rodents.

METHODS: Eyes were enucleated from fetuses in the 9th week of gestation, 1 week old piglets and 6 months old adult animals. Eyeglobes were fixed and cryosectioned. A panel of antibodies to well established retinal markers was employed for immunohistochemistry. Fluorescently labeled secondary antibodies were used for signal detection, and images were acquired by confocal microscopy. Mouse retina at postnatal day (P) 5 was used as a reference for this study to compare progression of histogenesis. Most of the primary antibodies have previously been used on mouse tissue.

RESULTS: Most of the studied markers were detected in midgestation pig retina, and the majority had a similar distribution in pig as in P5 mouse retina. However, rhodopsin immunolabeling was detected in pig retina at midgestation but not in P5 mouse retina. Contrary to findings in all rodents, horizontal cells were Islet1-positive and cones were calbindin-immunoreactive in pig retina, as has also been shown for the primate retina. Recoverin and rhodopsin immunolabeling revealed an increase in the length of photoreceptor segments in 6 months, compared to 1 week old animals.

CONCLUSIONS: Comparison with the published data on human retina revealed similar marker distribution and histogenesis progression in the pig and human retina, supporting the pig as a valuable animal model for studies on retinal disease and repair. Furthermore, this study provides information about the dynamics of retinal histogenesis in the pig and validates a panel of antibodies that reliably detects developing and mature retinal cell phenotypes in the pig retina.

Nerve Growth Factor Sensitisation of TRPA1 on Sensory Neurones

Background: Sensory neurones from the trigeminal nerve innervate the oro-facial region and teeth. Transient receptor potential channels (TRPs) expressed by these neurones are responsible for relaying sensory information such as changes in ambient temperature, mechanical sensations and pain. Study of TRP channel expression and regulation in human sensory neurones therefore merits investigation to improve our understanding of allodynia and hyperalgesia. Objective: The objective of this study was to differentiate human dental pulp stem cells (hDPSCs) towards a neuronal phenotype (peripheral neuronal equivalents; PNEs) and employ this model to study TRP channel sensitisation. Method: hDPSCs were enriched by preferential adhesion to fibronectin, plated on coverslips (thickness 0) coated with poly-l-ornithine and laminin and then differentiated for 7 days in neurobasal A medium with additional supplementation. A whole cell patch clamp technique was used to investigate whether TRP channels on PNE membranes were modulated in the presence of nerve growth factor (NGF). PNEs were treated with NGF for 20 minutes immediately before experimentation and then stimulated for TRPA1 activity using cinnamaldehyde. Peak currents were read at 80 mV and -80 mV and compared to peak currents recorded in untreated PNEs. Data were analysed and plotted using Clampfit9 software (Molecular Devices, Sunnyvale, California, USA). Result: Results showed for the first time that pre-treatment of PNEs by NGF produced significantly larger inward and outward currents demonstrating that TRPA1 channels on PNE membranes were capable of becoming sensitised following treatment with NGF. Conclusion: Sensitisation of TRPA1 by NGF provides evidence of a mechanism for rapid neuronal sensitisation that is independent of TRPA1 gene expression

Increasing the wear resistance of molds for injection of glass fiber reinforced plastics

Abrasion by glass fibers during injection molding of fiber reinforced plastics raises new challenges to the wear performance of the molds. In the last few decades, a large number of PVD and CVD coatings have been developed with the aim of minimizing abrasion problems. In this work, two different coatings were tested in order to increase the wear resistance of the surface of a mold used for glass fiber reinforced plastics: TiAlSiN and CrN/CrCN/DLC. TiAlSiN was deposited as a graded monolayer coating while CrN/CrCN/DLC was a nanostructured coating consisting of three distinct layers. Both coatings were produced by PVD unbalanced magnetron sputtering and were characterized using scanning electron microscopy (SEM) provided with energy dispersive spectroscopy (EDS), atomic force microscopy (AFM), micro hardness (MH) and scratch test analysis. Coating morphology, thickness, roughness, chemical composition and structure, hardness and adhesion to the substrate were investigated. Wear resistance was characterized through industrial tests with coated samples and an uncoated reference sample inserted in a feed channel of a plastic injection mold working with 30 wt.% glass fiber reinforced polypropylene. Results after 45,000 injection cycles indicate that the wear resistance of the mold was increased by a factor of 25 and 58, by the TiAlSiN and CrN/CrCN/DLC coatings, respectively, over the uncoated mold steel.

The Impact of Multifocal Intraocular Lens in Retinal Imaging with Optical Coherence Tomography

Multifocal intraocular lenses (MF IOLs) have concentric optical zones with different dioptric power, enabling patients to have good visual acuity at multiple focal points. However, several optical limitations have been attributed to this particular design. The purpose of this study is to access the effect of MF IOLs design on the accuracy of retinal optical coherence tomography (OCT). Cross-sectional study conducted at the Refractive Surgery Department of Central Lisbon Hospital Center. Twenty-three eyes of 15 patients with a diffractive MF IOL and 27 eyes of 15 patients with an aspheric monofocal IOL were included in this study. All patients underwent OCT macular scans using Heidelberg Spectralis®. Macular thickness and volume values and image quality (Q factor) were compared between the two groups. There were no statistically significant differences between both groups regarding macular thickness or volume measurements. Retinal OCT image quality was significantly lower in the MF IOL group (p < 0.01). MF IOLs are associated with a significant decrease in OCT image quality. However, this fact does not seem to compromise the accuracy of spectral domain OCT retinal measurements.

Differential effect of long versus short wavelength light exposure on pupillary re-dilation in patients with outer retinal disease.

BACKGROUND: In patients with outer retinal degeneration, a differential pupil response to long wavelength (red) versus short wavelength (blue) light stimulation has been previously observed. The goal of this study was to quantify differences in the pupillary re-dilation following exposure to red versus blue light in patients with outer retinal disease and compare them with patients with optic neuropathy and with healthy subjects. DESIGN: Prospective comparative cohort study. PARTICIPANTS: Twenty-three patients with outer retinal disease, 13 patients with optic neuropathy and 14 normal subjects. METHODS: Subjects were tested using continuous red and blue light stimulation at three intensities (1, 10 and 100 cd/m2) for 13 s per intensity. Pupillary re-dilation dynamics following the brightest intensity was analysed and compared between the three groups. MAIN OUTCOME MEASURES: The parameters of pupil re-dilation used in this study were: time to recover 90% of baseline size; mean pupil size at early and late phases of re-dilation; and differential re-dilation time for blue versus red light. RESULTS: Patients with outer retinal disease showed a pupil that tended to stay smaller after light termination and thus had a longer time to recovery. The differential re-dilation time was significantly greater in patients with outer retinal disease (median = 28.0 s, P < 0.0001) compared with controls and patients with optic neuropathy. CONCLUSIONS: A differential response of pupil re-dilation following red versus blue light stimulation is present in patients with outer retinal disease but is not found in normal eyes or among patients with visual loss from optic neuropathy.