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.

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.

A systematic literature review of surgical interventions for limbal stem cell deficiency in humans

PURPOSE: To evaluate the relative benefits and to identify any adverse effects of surgical interventions for limbal stem cell deficiency (LSCD).

DESIGN: Systematic literature review.

METHODS: We searched the following electronic databases from January 1, 1989 through September 30, 2006: MEDLINE, EMBASE, Science citation index, BIOSIS, and the Cochrane Library. In addition, reference lists were scanned to identify any additional reports. The quality of published reports was assessed using standard methods. The main outcome measure was improvement in vision of at least two Snellen lines of best-corrected visual acuity (BCVA). Data on adverse outcomes also were collected.

RESULTS: Twenty-six studies met the inclusion criteria. There were no randomized controlled studies. All 26 studies were either prospective or retrospective case series. For bilateral severe LSCD, keratolimbal allograft was the most common intervention with systemic immunosuppression. Other interventions included eccentric penetrating keratolimbal allografts and cultivated autologous oral mucosal epithelial grafts. An improvement in BCVA of two lines or more was reported in 31% to 67% of eyes. For unilateral severe LSCD, the most common surgical intervention was contralateral conjunctival limbal autograft, with 35% to 88% of eyes gaining an improvement in BCVA of two lines or more. The only study evaluating partial LSCD showed an improvement in BCVA of two lines or more in 39% of eyes.

CONCLUSIONS: Studies to date have not provided strong evidence to guide clinical practice on which surgery is most beneficial to treat various types of LSCD. Standardized data collection in a multicenter LSCD register is suggested.

Lipoxins attenuate renal fibrosis by inducing let-7c and suppressing TGFβR1

Lipoxins, which are endogenously produced lipid mediators, promote the resolution of inflammation, and may inhibit fibrosis, suggesting a possible role in modulating renal disease. Here, lipoxin A4 (LXA4) attenuated TGF-ß1-induced expression of fibronectin, N-cadherin, thrombospondin, and the notch ligand jagged-1 in cultured human proximal tubular epithelial (HK-2) cells through a mechanism involving upregulation of the microRNA let-7c. Conversely, TGF-ß1 suppressed expression of let-7c. In cells pretreated with LXA4, upregulation of let-7c persisted despite subsequent stimulation with TGF-ß1. In the unilateral ureteral obstruction model of renal fibrosis, let-7c upregulation was induced by administering an LXA4 analog. Bioinformatic analysis suggested that targets of let-7c include several members of the TGF-ß1 signaling pathway, including the TGF-ß receptor type 1. Consistent with this, LXA4-induced upregulation of let-7c inhibited both the expression of TGF-ß receptor type 1 and the response to TGF-ß1. Overexpression of let-7c mimicked the antifibrotic effects of LXA4 in renal epithelia; conversely, anti-miR directed against let-7c attenuated the effects of LXA4. Finally, we observed that several let-7c target genes were upregulated in fibrotic human renal biopsies compared with controls. In conclusion, these results suggest that LXA4-mediated upregulation of let-7c suppresses TGF-ß1-induced fibrosis and that expression of let-7c targets is dysregulated in human renal fibrosis.

Neural pathways mediating cross education of motor function

Cross education is the process whereby training of one limb gives rise to enhancements in the performance of the opposite, untrained limb. Despite interest in this phenomenon having been sustained for more than a century, a comprehensive explanation of the mediating neural mechanisms remains elusive. With new evidence emerging that cross education may have therapeutic utility, the need to provide a principled evidential basis upon which to design interventions becomes ever more pressing. Generally, mechanistic accounts of cross education align with one of two explanatory frameworks. Models of the 'cross activation' variety encapsulate the observation that unilateral execution of a movement task gives rise to bilateral increases in corticospinal excitability. The related conjecture is that such distributed activity, when present during unilateral practice, leads to simultaneous adaptations in neural circuits that project to the muscles of the untrained limb, thus facilitating subsequent performance of the task. Alternatively, 'bilateral access' models entail that motor engrams formed during unilateral practise, may subsequently be utilised bilaterally - that is, by the neural circuitry that constitutes the control centres for movements of both limbs. At present there is a paucity of direct evidence that allows the corresponding neural processes to be delineated, or their relative contributions in different task contexts to be ascertained. In the current review we seek to synthesise and assimilate the fragmentary information that is available, including consideration of knowledge that has emerged as a result of technological advances in structural and functional brain imaging. An emphasis upon task dependency is maintained throughout, the conviction being that the neural mechanisms that mediate cross education may only be understood in this context. © 2013 Ruddy and Carson.

Relationship between the magnitude of intraocular pressure during an episode of acute elevation and retinal damage four weeks later in rats

Purpose: To determine relationship between the magnitude of intraocular pressure (IOP) during a fixed-duration episode of acute elevation and the loss of retinal function and structure 4 weeks later in rats.

Methods: Unilateral elevation of IOP (105 minutes) was achieved manometrically in adult Brown Norway rats (9 groups; n = 4 to 8 each, 10–100 mm Hg and sham control). Full-field ERGs were recorded simultaneously from treated and control eyes 4 weeks after IOP elevation. Scotopic ERG stimuli were white flashes (26.04 to 2.72 log cd.s.m^-2). Photopic ERGs were recorded (1.22 to 2.72 log cd.s.m22) after 15 min of light adaptation (150 cd/m2). Relative amplitude (treated/control, %) of ERG components versus IOP was described with a cummulative normal function. Retinal ganglion cell (RGC) layer density was determined post mortem by histology.

Results: All ERG components failed to recover completely normal amplitudes by 4 weeks after the insult if IOP was 70 mmHg or greater during the episode. There was no ERG recovery at all if IOP was 100 mmHg. Outer retinal (photoreceptor) function demonstrated the least sensitivity to prior acute IOP elevation. ERG components reflecting inner retinal function were correlated with post mortem RGC layer density.

Conclusions: Retinal function recovers after IOP normalization, such that it requires a level of acute IOP elevation approximately 10 mmHg higher to cause a pattern of permanent dysfunction similar to that observed during the acute event. There is a ‘threshold’ for permanent retinal functional loss in the rat at an IOP between 60 and 70 mmHg if sustained for 105 minutes or more.

Delaying Truth Recovery for Missing Persons

The fate of missing persons is a central issue in post-conflict societies facing truth recovery and human rights dilemmas. Despite widespread public sympathy towards relatives, societies emerging from conflict often defer the recovery of missing for decades. More paradoxically, in post-1974 Cyprus, the official authorities delayed unilateral exhumations of victims buried within cemeteries in their own jurisdiction. Analysis of official post-1974 discourse reveals a Greek-Cypriot consensus to emphasise the issue as one of Turkish aggression, thus downplaying in-group responsibilities and the legacy of intra-communal violence. We compare the experience of Cyprus with other post-conflict societies such as Spain, Northern Ireland, and Mozambique and explore the linkages between institutions and beliefs about transitional justice. We argue that elite consensus initiates and facilitates the transition to democracy but often leads to the institutionalization of groups opposing truth recovery even for in-group members.

Inter-Agency Evidence Sharing in Competition Law Enforcement

While transnational antitrust enforcement is becoming only more common, the access to foreign-based evidence remains a considerable practical challenge. This article appraises considerations and concerns surrounding confidentiality, and looks into ways of their possible accommodation. It further identifies and critically evaluates the existing mechanisms allowing for inter-agency confidential information/ evidence sharing in competition law enforcement. The article outlines the shortcomings of the current framework and points to novel unilateral approaches. In the latter regard the focus is devoted to Australia, where the competition agency is empowered to share confidential information with foreign counterparts, also without any underlying bilateral agreement and on a non-reciprocal basis. This solution shows that a pragmatic and workable approach to inter-agency evidence sharing can be achieved.

Chromosome synapsis and recombination in simple and complex chromosomal heterozygotes of tuco-tuco (Ctenomys talarum: Rodentia: Ctenomyidae):Rodentia: Ctenomyidae)

The chromosomal speciation hypothesis suggests that irregularities in synapsis, recombination, and segregation in heterozygotes for chromosome rearrangements may restrict gene flow between karyotypically distinct populations and promote speciation. Ctenomys talarum is a South American subterranean rodent inhabiting the coastal regions of Argentina, whose populations polymorphic for Robertsonian and tandem translocations seem to have a very restricted gene flow. To test if chromosomal differences are involved in isolation among its populations, we examined chromosome pairing, recombination, and meiotic silencing of unsynapsed chromatin in male meiosis of simple and complex translocation heterozygotes using immunolocalization of the MLH1 marking mature recombination nodules and phosphorylated histone γH2A.X marking unrepaired double-strand breaks. We observed small asynaptic areas labeled by γH2A.X in pericentromeric regions of the chromosomes involved in the trivalents and quadrivalents. We also observed a decrease of recombination frequency and a distalization of the crossover distribution in the heterozygotes and metacentric homozygotes compared to acrocentric homozygotes. We suggest that the asynapsis of the pericentromeric regions are unlikely to induce germ cell death and decrease fertility of the heterozygotes; however, suppressed recombination in pericentromeric areas of the multivalents may reduce gene flow between chromosomally different populations of the Talas tuco-tuco.

EU Cross-Border Cooperation and Conflict Transformation in the Basque and Irish Border Regions

Comparative research on violent conflict in the Basque Country and Ireland has yielded a sizable body of published academic work. Less well explored is the relationship between conflict transformation and cross-border cooperation in that specific comparative context. This paper provides a comparative examination of Third (not for profit) sector cross-border cooperation as conflict transformation in the Basque (France/Spain) and Irish (UK/Ireland) border regions. To what extent does cross-border cooperation contribute to peacebuilding in the two last violent ethnonationalist conflicts in Western Europe? The comparison is based on the premise that the EU played a different role in both cases. In the Irish case, the EU contributed to the institutionalization of a peace process that included cross-border cooperation between third sector organizations among the policy instruments contributing to conflict transformation. In the Basque case, the unilateral renunciation of violence by ETA (Euskadi eta Askatasuna) in 2010 did not generate the consistent involvement of the EU in a comparable institutional peace process. However, some third sector organizations used EU instruments for cross-border economic, social and cultural cooperation between France and Spain in order to reinforce their cross-border networks, which indirectly impacted on conflict transformation. The effectiveness of this cross-border cooperation for conflict transformation is assessed comparatively. To what extent does this increase in cross-border cooperation “from below” connect to wider institutional and social processes of conflict transformation in Ireland and the Basque Country? Crucially, does the strengthening of cross-border relations on shared issues mollify or sharpen existing identity cleavages? Also considered is the sustainability of such cooperation in these regions in light of the less favourable post-2004 EU funding environment, and the post-2008 economic and political turmoil affecting the relevant EU member states, especially Ireland and Spain.

Outcomes and projected impact on vision restoration of the China million cataract surgeries program

Purpose: The recently completed Chinese "Million Cataract Surgeries Program" (MCSP) is among the largest such campaigns ever, providing 1.05 million operations. We report MCSP outcomes for the first time, in Jiangxi, the province with the greatest program output. Methods: Ten county hospitals participating in MCSP were selected in Jiangxi (range of gross domestic product per capita US$743-2998). Each hospital sought to enroll 75 consecutive MCSP patients aged ≥50 years. Data recorded included type of cataract procedure, bilateral uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), and refractive error pre- and ≥50 days postoperatively. Results: Among 715 patients (mean age 72.3±9.1 years, 55.5% female), preoperative UCVA was <3/60 (legally blind) bilaterally in 13.3% and unilaterally in the operated eye in 50.9%. No subjects had UCVA >6/18 preoperatively. Small incision cataract surgery was performed in 92.3% patients. Among 662 patients (92.6%) completing follow-up was ≥ 40 days after surgery, BCVA was ≥6/18 in 80.1%, UCVA was ≥6/18 in 57.1% and UCVA was <3/60 in 2.1%. Older age (p<0.001), female sex (p=0.04), worse refractive error (p=0.02) and presence of intra- (p=0.002) and postoperative surgical complications (p<0.001), were independently associated with worse postoperative UCVA. Based on these results, the MCSP cured an estimated 124,950 cases (13.3%×[100-2.1%]×1.05 million) of bilateral and 502,500 (50.9%×[100-2.1%]×1.05 million) of unilateral blindness. Conclusions: Due to relatively good outcomes and the large number of surgeries performed on blind persons, the sight-restoring impact of the MCSP was probably substantial. © Informa Healthcare USA, Inc.

Determinants of pediatric cataract program outcomes and follow-up in a large series in Mexico.

PURPOSE:

To report determinants of outcomes and follow-up in a large Mexican pediatric cataract project.

SETTING:

Hospital Luis Sanchez Bulnes, Mexico City, Mexico.

METHODS:

Data were collected prospectively from a pediatric cataract surgery program at the Hospital Luis Sanchez Bulnes, implemented by Helen Keller International. Preoperative data included age, sex, baseline visual acuity, type of cataract, laterality, and presence of conditions such as amblyopia. Surgical data included vitrectomy, capsulotomy, complications, and use of intraocular lenses (IOLs). Postoperative data included final visual acuity, refraction, number of follow-up visits, and program support for follow-up.

RESULTS:

Of 574 eyes of 415 children (mean age 7.1 years +/- 4.7 [SD]), IOLs were placed in 416 (87%). At least 1 follow-up was attended by 408 patients (98.3%) (mean total follow-up 3.5 +/- 1.8 months); 40% of eyes achieved a final visual acuity of 6/18 or better. Children living farther from the hospital had fewer postoperative visits (P = .04), while children receiving program support had more visits (P = .001). Factors predictive of better acuity included receiving an IOL during surgery (P = .04) and provision of postoperative spectacles (P = .001). Predictive of worse acuity were amblyopia (P = .003), postoperative complications (P = .0001), unilateral surgery (P = .0075), and female sex (P = .045).

CONCLUSIONS:

The results underscore the importance of surgical training in reducing complications, early intervention before amblyopia (observed in 40% of patients) can develop, and vigorous treatment if amblyopia is present. The positive impact of program support on follow-up is encouraging, although direct financial support may pose a problem for sustainability. More work is needed to understand reasons for worse outcomes in girls.

Neural adaptations associated with interlimb transfer in a ballistic wrist flexion task.

Cross education is the process whereby training of one limb gives rise to increases in the subsequent performance of its opposite counterpart. The execution of many unilateral tasks is associated with increased excitability of corticospinal projections from primary motor cortex (M1) to the opposite limb. It has been proposed that these effects are causally related. Our aim was to establish whether changes in corticospinal excitability arising from prior training of the opposite limb determine levels of interlimb transfer.

We used three vision conditions shown previously to modulate the excitability of corticospinal projections to the inactive (right) limb during wrist flexion movements performed by the training (left) limb. These were: mirrored visual feedback of the training limb; no visual feedback of either limb; and visual feedback of the inactive limb. Training comprised 300 discrete, ballistic wrist flexion movements executed as rapidly as possible. Performance of the right limb on the same task was assessed prior to, at the mid point of, and following left limb training.

There was no evidence that variations in the excitability of corticospinal projections (assessed by transcranial magnetic stimulation (TMS)) to the inactive limb were associated with, or predictive of, the extent of interlimb transfer that was expressed. There were however associations between alterations in muscle activation dynamics observed for the untrained limb, and the degree of positive transfer that arose from training of the opposite limb.

The results suggest that the acute adaptations that mediate the bilateral performance gains realised through unilateral practice of this ballistic wrist flexion task are mediated by neural elements other than those within M1 that are recruited at rest by single-pulse TMS.

A Systematic Review of End-of-Life Visual Impairment in Open-Angle Glaucoma: An Epidemiological Autopsy

PURPOSE: Glaucoma patients are still at risk of becoming blind. It is of clinical significance to determine the risk of blindness and its causes to prevent its occurrence. This systematic review estimates the number of treated glaucoma patients with end-of-life visual impairment (VI) and blindness and the factors that are associated with this.

METHODS: A systematic literature search in relevant databases was conducted in August 2014 on end-of-life VI. A total of 2574 articles were identified, of which 5 on end-of-life VI. Several data items were extracted from the reports and presented in tables.

RESULTS: All studies had a retrospective design. A considerable number of glaucoma patients were found to be blind at the end of their life; with up to 24% unilateral and 10% bilateral blindness. The following factors were associated with blindness: (1) baseline severity of visual field loss: advanced stage of glaucoma or substantial visual field loss at the initial visit; (2) factors influencing progression: fluctuation of intraocular pressure (IOP) during treatment, presence of pseudoexfoliation, poor patient compliance, higher IOP; (3) longer time period: longer duration of disease and older age at death because of a longer life expectancy; and (4) coexistence of other ocular pathology.

CONCLUSIONS: Further prevention of blindness in glaucoma patients is needed. To reach this goal, it is important to address the risk factors for blindness identified in this review, especially those that can be modified, such as advanced disease at diagnosis, high and fluctuating IOP, and poor compliance.