Search

The retina, the accessible part of the central nervous system, has served as a model system to study the relationship between energy utilization and metabolite supply. When the metabolite supply cannot match the energy demand, retinal neurons are at risk of death. As the powerhouse of eukaryotic cells, mitochondria play a pivotal role in generating ATP, produce precursors for macromolecules, maintain the redox homeostasis, and function as waste management centers for various types of metabolic intermediates. Mitochondrial dysfunction has been implicated in the pathologies of a number of degenerative retinal diseases. It is well known that photoreceptors are particularly vulnerable to mutations affecting mitochondrial function due to their high energy demand and susceptibility to oxidative stress. However, it is unclear how defective mitochondria affect other retinal neurons. Nuclear respiratory factor 1 (Nrf1) is the major transcriptional regulator of mitochondrial biogenesis, and loss of Nrf1 leads to defective mitochondria biogenesis and eventually cell death. Here, we investigated how different retinal neurons respond to the loss of Nrf1. We provide in vivo evidence that the disruption of Nrf1-mediated mitochondrial biogenesis results in a slow, progressive degeneration of all retinal cell types examined, although they present different sensitivity to the deletion of Nrf1, which implicates differential energy demand and utilization, as well as tolerance to mitochondria defects in different neuronal cells. Furthermore, transcriptome analysis on rod-specific Nrf1 deletion uncovered a previously unknown role of Nrf1 in maintaining genome stability.

AimTo evaluate the quality of oral fluorescein angiography (FA) in relation to food intake.MethodsThis is an observational, case-crossover study. We collected information from patients undergoing routine oral FA for retinal disease at the Shiley Eye Institute. Eighty patients (160 eyes) were analysed. Fasting and non-fasting images of the same patient were recorded, compared and analysed for different image quality parameters and clinical relevance by experienced retina specialists.ResultsWhen analysing the images, intergrader agreement was moderate to good with a Kappa averaging 0.60 (0.5–0.85). When patients were fasting pre-imaging, better angiography quality scores were achieved when compared with images taken when patients were non-fasting (mean 0.84 vs 0.72, pConclusionFasting oral FA provided significantly better quality images as well as faster optimal imaging times when compared with non-fasting oral FA. By improving its overall quality, oral FA could be a useful adjunctive examination to optical coherence tomography (OCT) and OCT angiography in patients who require FA studies but who have difficult access or refuse an invasive procedure.

Pathological biomolecules such as lipofuscin, methylglyoxal-modified proteins (the major precursors of advanced glycationend products), misfolding protein deposits and dysfunctional mitochondria are source of oxidative stress and act as strong autophagic stimulators in age-related macular degeneration. Disturbed autophagy accelerates progression of the disease, since it leads to retinal cells’ death and activates inflammation by the interplay with the NLRP3 inflammasome complex. Vascular dysfunction and hypoxia, as well as circulating autoantibodies against autophagy regulators (anti-S100A9, anti-ANXA5, and anti-HSPA8, A9 and B4) compromise an autophagy-mediated mechanism as well. Metformin, the autophagic stimulator, may act as a senostatic drug to inhibit the senescent phenotype in the age-related macular degeneration. PGC-1α , Sirt1 and AMPK represent new therapeutic targets for interventions in this disease., EXCLI Journal;Vol. 19. 2020, pp. 1353-1371

Background Treatment of Plasmodium vivax malaria requires the clearing of asexual parasites, but relapse can be prevented only if dormant hypnozoites are cleared from the liver (a treatment termed “radical cure”). Tafenoquine is a single-dose 8-aminoquinoline that has recently been registered for the radical cure of P. vivax. Methods This multicenter, double-blind, double-dummy, parallel group, randomized, placebo-controlled trial was conducted in Ethiopia, Peru, Brazil, Cambodia, Thailand, and the Philippines. We enrolled 522 patients with microscopically confirmed P. vivax infection (>100 to Results In the intention-to-treat population, the percentage of patients who were free from recurrence at 6 months was 62.4% in the tafenoquine group (95% confidence interval [CI], 54.9 to 69.0), 27.7% in the placebo group (95% CI, 19.6 to 36.6), and 69.6% in the primaquine group (95% CI, 60.2 to 77.1). The hazard ratio for the risk of recurrence was 0.30 (95% CI, 0.22 to 0.40) with tafenoquine as compared with placebo (P Conclusions Single-dose tafenoquine resulted in a significantly lower risk of P. vivax recurrence than placebo in patients with phenotypically normal G6PD activity. (Funded by GlaxoSmithKline and Medicines for Malaria Venture; DETECTIVE ClinicalTrials.gov number, NCT01376167. opens in new tab.)

Optical coherence tomography angiography (OCT-A) is a non-invasive, non-dye-based imaging modality that has the potential to enhance our understanding of retinal diseases. While this rapidly advancing imaging modality offers great potential, there is a need for community-wide understanding of the range of technologies and methods for interpreting the images, as well as a need to enhance understanding of images from disease-free eyes for reference when screening for retinal diseases. Importantly, clinical trials have been designed without OCT-A-based endpoints; therefore, caution is required when making treatment decisions based on OCT-A imaging alone. With this in mind, a full understanding of the advantages and limitations of OCT-A will be vital for effective development of the technique within the field of ophthalmology. On behalf of the Vision Academy Steering Committee (sponsored by Bayer), this publication summarizes the views of the authors on the current use of OCT-A imaging and explores its potential for future applications in research and clinical practice. © 2018, The Author(s).

cited By 0; Purpose: The main objective of this study was to assess choroidal thickness (CT) changes during an exudative recurrence of age-related macular degeneration (AMD). Methods: A real-life prospective non-interventional 9-month study was conducted in two centers in consecutive patients with exudative AMD between November 2016 and July 2017. CT was measured manually in both eyes based on enhanced-depth imaging spectral-domain optical coherence tomography at different follow-up visits scheduled in the morning. Results: A total of 134 patients were included. Ninety-five patients presented at least one episode, defined by a follow-up visit under controlled condition (dry retina) followed by a visit for exudative recurrence. A total of 119 episodes were analyzed. The mean CT change in the treated eye was + 8.45 ± 13.52 μm (p < 0.001) and + 5.62 ± 14.77 μm (p = 0.009) respectively in the subfoveal area and nasal area. No significant change in CT was observed in the fellow eye. No significant association between CT changes and treatment, number of intravitreal injections, and blood pressure was observed. Conclusion: CT increased in case of exudative recurrence of neovascular AMD. The increase was mild but significant. Thus, CT could be used as a monitoring criterion, like the central retinal thickness, in AMD management. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

Purpose: Reporting clinical features of the late course of the disease after long-term follow-up in a bilaterally affected patient with idiopathic retinitis, vasculitis, retinal aneurysms and neuroretinitis (IRVAN) and new peripheral retinal findings on wide-field angiography and multimodal imaging. Methods: This was a retrospective observational study, based on current diagnostic studies including wide-field fluorescein angiography, optical coherence tomography (OCT) and treatment of aneurysms with argon laser photocoagulation. Results: A 21-year-old female with bilateral IRVAN syndrome—stage 2 in the right eye and stage 3 in the left eye—previously treated bilaterally with laser photocoagulation for retinal macroaneurysms and ischemic areas between 1985 and 1992. Follow-up interrupted on two occasions, with subsequent fundus re-examinations confirming the prevention of retinal neovascularization in both eyes, as recently evidenced on wide-field angiography. Conclusions: A case of bilateral IRVAN disease with multiple retinal aneurysms, neuroretinitis and peripheral capillary nonperfusion successfully treated with laser photocoagulation, maintaining normal visual acuity in one eye and preventing retinal neovascular complications. © 2018, Springer Science+Business Media B.V., part of Springer Nature.

Purpose To review the evolution and usefulness of ultra widefield images of the retina. Method Literature review. Results The ability to obtain images of the ocular fundus is one of the greatest breakthroughs in our specialty. This ability has refined over time, from obtaining images with a field of 30 degrees, to obtaining images that exceed 150 degrees using equipment such as the Optos Daytona (Optos, Dunfermline, United Kingdom) or the Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany). These images are extremely useful to evaluate diseases such as diabetic retinopathy, retinal vascular occlusions, pediatric retinal pathology, posterior uveitis, and even diseases which classically affect the macula such as age-related macular degeneration. Conclusion Ultra widefield images of the retina have revolutionized the way we study and understand retinal pathology. As technology for obtaining these images becomes more accessible, it will surely become part of the routine evaluation of retinal diseases. © 2016 Sociedad Mexicana de Oftalmología

WOS: 000410594600003, PubMed ID: 28731058, Purpose To evaluate surgical intervention with pars plana vitrectomy (PPV) for correction of optic disc pit maculopathy (ODP-M). Patients and methods Retrospective chart review from 13 centres of 51 eyes of 50 patients with ODP-M who underwent PPV between 2002-2014. Anatomic and final best-corrected visual acuity (BCVA) outcomes were evaluated for all cases with different adjuvant techniques. Results There were 23 males and 27 females with median age 25.5 (6-68) years. Preoperative median foveal thickness was 694.5 (331-1384) mu m and improved to 252.5 (153-1405) mu m. Median BCVA improved from 20/200 (20/20000 to 20/40) to 20/40 (20/2000 to 20/20) with 20/40 or better in 31 eyes. Complete retinal reattachment was achieved in 44 eyes (86.3%) at 7.1 (5.9) months. The good surgical outcomes were achieved in different adjuvant groups. Median follow-up was 24 (6 to 120) months. Conclusions These results confirm the long-term effectiveness of PPV for ODP-M. Prospective studies are needed to determine the effectiveness of any adjuvant technique in improving the success of PPV for ODP-M.

Purpose To review the evolution and usefulness of ultra widefield images of the retina. Method Literature review. Results The ability to obtain images of the ocular fundus is one of the greatest breakthroughs in our specialty. This ability has refined over time, from obtaining images with a field of 30 degrees, to obtaining images that exceed 150 degrees using equipment such as the Optos Daytona (Optos, Dunfermline, United Kingdom) or the Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany). These images are extremely useful to evaluate diseases such as diabetic retinopathy, retinal vascular occlusions, pediatric retinal pathology, posterior uveitis, and even diseases which classically affect the macula such as age-related macular degeneration. Conclusion Ultra widefield images of the retina have revolutionized the way we study and understand retinal pathology. As technology for obtaining these images becomes more accessible, it will surely become part of the routine evaluation of retinal diseases. © 2016 Sociedad Mexicana de Oftalmología

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:27:06Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:42:27Z : No. of bitstreams: 1 2-s2.0-84869206693.pdf: 345052 bytes, checksum: af1f663f5bb60b9d0121f6ed18b7e210 (MD5) Made available in DSpace on 2014-05-27T11:27:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-10-23 Amino acids are well known to be an important class of compounds for the maintenance of body homeostasis and their deficit, even for the polar neuroactive aminoacids, can be controlled by supplementation. However, for the amino acid taurine (2-aminoethanesulfonic acid) this is not true. Due its special physicochemical properties, taurine is unable to cross the blood-brain barrier. In addition of injured taurine transport systems under pathological conditions, CNS supplementation of taurine is almost null. Taurine is a potent antioxidant and anti-inflammatory semi-essential amino acid extensively involved in neurological activities, acting as neurotrophic factor, binding to GABA A/glycine receptors and blocking the excitotoxicity glutamate-induced pathway leading to be a neuroprotective effect and neuromodulation. Taurine deficits have been implicated in several CNS diseases, such as Alzheimer's, Parkinson's, epilepsy and in the damage of retinal neurons. This review describes the CNS physiological functions of taurine and the development of new derivatives based on its structure useful in CNS disease treatment.&; 2012 by the authors; licensee MDPI, Basel, Switzerland. Lapdesf-Laboratory of Drug Design School of Pharmaceutical Sciences University of São Paulo State (UNESP), Rodovia Araraquara-Jaú Km1, CEP 14.801-902, Araraquara, SP Lapdesf-Laboratory of Drug Design School of Pharmaceutical Sciences University of São Paulo State (UNESP), Rodovia Araraquara-Jaú Km1, CEP 14.801-902, Araraquara, SP

PURPOSE: To report the visual outcomes and ocular complications of intravitreal triamcinolone acetonide (IVTA) in the treatment of the nonproliferative stage of type II idiopathic parafoveal telangiectasia (IPT). METHODS: Retrospective, multicenter, uncontrolled interventional case series of 19 eyes of 14 consecutive patients with the nonproliferative stage of IPT that had undergone at least one intravitreal injection of 4 mg of triamcinolone acetonide. Demographic, medical, and ocular data were obtained through chart review. The main outcome measures included best-corrected visual acuity at several timepoints of follow up and ocular complications. RESULTS: At baseline the mean logMAR visual acuity was 0.83 ± 0.41 (Snellen 20/135, range 0.3-2). After an average follow-up of 21.2 months (range 6-44 months), the mean logMAR visual acuity remained essentially unchanged from baseline. At 3 months, the logMAR visual acuity was 0.86 ± 0.44 (Snellen 20/145, P = 0.8378), at 6 months 0.86 ± 0.42 (Snellen 20/145, P = 0.8149), at 12 months 0.87 ± 0.46 (Snellen 20/148, P > 0.9999), at 18 months 0.84 ± 0.35 (Snellen 20/138, P = 0.8385), and at the last follow-up 0.82 ± 0.44 (Snellen 20/132, P = 0.9301). Seven eyes were reinjected once. Ten of 19 eyes (53%) developed cataract (3 eyes underwent phacoemulsification and intraocular lens implantation) and 7 of 19 eyes (37%) had an elevated intraocular pressure, none of which required surgical treatment. CONCLUSION: IVTA does not seem to improve visual acuity in most eyes with the nonproliferative stage of IPT. © The Ophthalmic Communications Society, Inc.

Purpose To report a case of epiretinal macular membrane and a lamellar macular hole developing after the spontaneous separation of an idiopathic vitreoretinal traction. Methods Retrospective, observational, long follow-up of a case evaluated and documented with optical coherence tomography and managed with current therapies including pars plana vitrectomy. Results Good anatomic and functional results with stable 20/30 best-corrected visual acuity. Conclusions The natural course of idiopathic vitreomacular traction has been documented during prolonged observation after its spontaneous separation from the fovea leading to the development of an epiretinal membrane and a lamellar macular hole.

cited By 17; International audience; Aim To assess the effectiveness and safety of intravitreal dexamethasone implants for treating post-surgical macular oedema, including Irvine-Gass syndrome refractory to first-line treatments. Methods Descriptive, observational, retrospective, consecutive, uncontrolled, multicentre, national case series. 50 patients were included in the study between March 2011 and June 2013 with a minimum 6 months follow-up. At baseline, each patient received a dexamethasone implant 0.7 mg (Ozurdex). Best-corrected visual acuity (BCVA), central subfield macular thickness (CSMT), and intraocular pressure (IOP) were measured at baseline and then monthly. The main outcome measure was the mean change in BCVA (in ETDRS letters (Early Treatment Diabetic Retinopathy Study): L) Results Baseline mean±SD BCVA was 55.7±15.4 L. At month 2, BCVA was 71.8±10.5 L and 61.2% of patients had an increase of more than 15 letters. Baseline mean CSMT was 544±117.2 μm and this decreased to 302 μm at month 2. Anatomic and functional recurrences were both first detected from month 3 and continued throughout follow-up, with values consistently above baseline. The peak in IOP was reached in month 1 with mean IOP of 15.3±4.6 mm Hg. Of the 39/50 patients followed up for 12 months, 49% received a second injection. The anatomic and functional response and safety patterns were similar to that obtained with the first intravitreal injection, demonstrating Ozurdex's reproducibility. However, more than half of the patients followed-up for at least 1 year presented neither functional nor anatomical recurrence. Conclusions Ozurdex would appear to be an interesting alternative therapy for treating post-surgical macular oedema, including Irvine-Gass syndrome refractory to first-line treatments.

PURPOSE To investigate the use of spectral domain optical coherence tomography (SD-OCT) findings in pediatric acute lymphoblastic leukemia (ALL) patients. METHODS Children that were diagnosed with precursor B-cell ALL and classified as belonging to the medium-risk group for relapse were selected for this study. Individuals who were in. continuous remission and on maintenance therapy were included in the study group. Cases that had central nervous system involvement were excluded. Age-matched, otherwise healthy children were selected for the control group. Each study participant underwent a comprehensive eye examination and SD-OCT evaluation. Thickness measurements were made within the retinal nerve fiber layer (RNFL), central macula, posterior polar, and peripapillary choroid. RESULTS A total of 112 eyes of 56 children were included: 54 eyes in the study group and 58 in the control group. Compared to the control group, subfoveal and temporal choroidal thicknesses of the posterior pole were significantly thinner in the study group (P < 0.005). Similarly, peripapillary choroidal thicknesses were significantly thinner in most sectors of the study group (P < 0.005). There were no major differences between groups in terms of central macular thicknesses and overall RNFL thicknesses. CONCLUSIONS Evidence of choroidal attenuation was found in this subgroup of pediatric ALL patients. Further studies are warranted to clarify the utility of SD-OCT in detecting subclinical ocular involvement and monitoring treatment response and risk of relapse in patients with pediatric leukemia.

Objective: To report the prevalence of age-related maculopathy (ARM) in Salandra, a small, isolated southern Italian community, to test the hypothesis that an environmental factor, scarce in such a remote community but ubiquitous in modern industrial societies, might modify the risk of developing ARM. Design: Population-based cross-sectional survey. Main Outcome Measures: Prevalence of advanced age-related macular degeneration (ARMD) (geographic atrophy or exudative maculopathy) and ARM (large, soft drusen or retinal pigment epithelium changes, or both) defined by fundus biomicroscopy and 30° stereoscopic macular photography. Self-sustenance was assessed by interview of participants and local shop retailers. The degree of genetic isolation was computed using a model that fits the genetic population structure with the frequency distribution of surnames in the community. Results: A full ophthalmic examination was undertaken in 366 (63.5%) of 576 eligible participants, 354 (96.7%) of whom had clinical or photographic assessment for the presence of ARMD and 310(84.6%) of whom had drusen characteristics graded on color transparencies for ARM. The overall prevalence of ARMD was 1.1%. Drusen larger than 50 μm and more numerous than 10 were found in 4.5% of subjects. Salandra was the birthplace of 87.2% of participants and for 77.3% of both parents of each subject. People in the community tended to consume homegrown products. Conclusion: The prevalence of ARM may be lower in this self-sustained farming community than elsewhere in the industrialized world.