Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues.Pyrroloquinoline quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary administration.Pyrroloquinoline quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many studies.In this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian life.Through the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and death.Pyrroloquinoline quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully elucidated.Here,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological contexts.In addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

Glycolysis and glucose metabolism as a target for bioenergetic and neuronal protection in glaucoma

Vision is arguably our most valued sense,yet approximately 340 million people globally suffer blindness or moderate visual impairment,highlighting the need to further develop and advance treatments for ophthalmic diseases.Glaucoma refers to a group of ocular disorders united by a clinically characteristic optic neuropathy with associated retinal ganglion cell loss.

XEN Gel Stent exposure 7mo after primary implantation:a case report

Dear Editor,XEN Gel Stent 45 gm (Allergan Pic, Irvine, CA, USA) is a minimally-invasive procedure in glaucoma surgery perceived to reduce the risk of postoperative hypotony while sufficiently lowering the intraocular pressure (IOP) and requiring less topical antiglaucoma medications postoperatively.

The Anatomical Dry Eye <br/>—A Different Form of Ocular Surface Disease Deserves Focus

Introduction: Dry eye disease is currently considered mainly tear film related ocular surface condition. This concept does, however, not respect ocular surface topography. The micro-anatomy of the corneal changes may lead to enhanced demands on the tear film and lead to significant complaints. However, they often remain undetected and hence untreated. It is suggested that the pathophysiology for an entire subgroup of dry eye disease patients is primarily of surface morphological nature. Methods: The tear film break up was observed and used to identify anatomical alterations in eyes of patients with dry eye complaints. The localization and pattern of TFBUT using fluorescein was compared between eye with normal surfaces and surface alterations. Results: Premature tear film rupture was localized at constantly same areas and did match changes on the ocular epitheliopathy in patients with diseases such as microcystic epithliopathy, MFD, and after excimer laser treatment. Disusssion: Whereas in normal surfaces TFBUT does occur within the floating tear film, the anatomical dry eye identifies itself with constant location of tear film break up and a constant spreading pattern. In contrast to the classic, tear film caused dry eye, the anatomical dry eye is accessible to treatment. This should catch our attention and intent to identify it. It is the ease of possible treatment that should make these ocular surface alterations prime target of dry eye disease diagnostic. It is hence suggested to introduce the anatomical dry eye as a subgroup in the large group of dry eye and ocular surface disease.

An international survey of classification and treatment choices for group D retinoblastoma

AIM： To determine which IIRC scheme was used by retinoblastoma centers worldwide and the percentage of D eyes treated primarily with enucleation versus globe salvaging therapies as well as to correlate trends in treatment choice to IIRC version used and geographic region. METHODS： An anonymized electronic survey was offered to 115 physicians at 39 retinoblastoma centers worldwide asking about IIRC classification schemes and treatment patterns used between 2008 and 2012. Participants were asked to record which version of the IIRC was used for classification, how many group D eyes were diagnosed, and how many eyes were treated with enucleation versus globe salvaging therapies. Averages of eyes per treatment modality were calculated and stratified by both IIRC version and geographic region. Statistical significance was determined by Chi-square, ANOVA and Kruskal-Wallis tests using Prism. RESULTS： The survey was completed by 29% of physicians invited to participate. Totally 1807 D eyes were diagnosed. Regarding IIRC system, 27% of centers used the Children＇s Hospital of Los Angeles （CHLA） version, 33% used the Children＇s Oncology Group （COG） version, 23% used the Philadelphia version, and 17% were unsure. The rate for primary enucleation varied between 0 and 100% and the mean was 29%. By IIRC version, primary enucleation rates were： Philadelphia, 8%; COG, 34%; and CHLA, 37%. By geographic region, primary enucleation rates were： Latin America, 57%; Asia, 40%; Europe, 36%; Africa, 10%, US, 8%; and Middle East, 8%. However, systemic chemoreduction was used more often than enucleation in all regions except Latin America with a mean of 57% per center （P〈0.0001）. CONCLUSION： Worldwide there is no consensus on which IIRC version is used, systemic chemoreduction was the most frequently used initial treatment during the study period followed by enucleation and primary treatment modality, especially enucleation, varied greatly with regards to IIRC version used and geographic region.

无红光数字图像与色彩透明化图像检出糖尿病性视网膜病变的比较

Background: The aim of this study was to compare how diabetic retinopathy was detected from red-free digital images and colour transparencies. Methods: Two o phthalmologists graded two-field, nonster eoscopic, 60°red-free digital image s and colour transparencies utilizing an ETDRS-based grading scale, from 107 ma inly type 2 diabetic patients. The discordantly scored eyes were graded by the g raders together to obtain a consensus level of retinopathy for each method. The eyes with discordant consensus grading results were further graded using all ava ilable photographic material to reach a final consensus level of diabetic retino pathy. Intermethod variations were presented as percentages and using kappa (k) and weighted kappa (wk) statistics. The errors of the two consensus gradings wit h respect to the final consensus grading were compared using McNemar’s test. Re sults: For the colour transparencies there was an agreement between the individu al and the consensus grading results in 93%(k=0.90, wk=0.97) and 86%(k=0.79, w k 0.88) for grader 1 and grader 2. Corresponding figures for red-free digital i mages were 88%(k=0.83, wk=0.96) and 84%(k=0.78, wk 0.91). Agreement between me thods was obtained in 76/107 eyes (71%; k=0.58 and wk=0.79). In the 31 discorda ntly graded eyes the level of retinopathy was underestimated in 20/31 (64%) vs 7/31 eyes (23%) and overestimated in 1/31 (3%) vs 3/31 eyes (10%) from colour transparencies and red-free digital images, respectively. The error tendencies were significantly lower when using red-free digital images (p < 0.008). Concl usions: Red-free digital images are comparable with two-field colour transpare ncies in the identification of mild to moderate nonproliferative diabetic retino pathy.

Suicide after Excimer Laser Refractive Surgery: On the Importance of Matching Expectations

Background: Refractive surgery may change the individual life to the better largely eliminating the need for spectacles. However, expectations may vary and postoperative reality may come as a surprise. Aim: To emphasize the need for thorough alignment of expectations and options between surgeon and patient. Methods: A case is presented in which a successful refractive laser operation is a part of a trigger mechanism for a depressive episode leading to suicide. It emphasizes the crucial importance of constructive alignment of expectations between patient and treating physician prior to surgery. Results: The case presented outlines that ophthalmic surgery at the edge of high-tec with all its tempting features is also very attractive to individuals with very well defined and less flexible expectations. The possible irreversibility of some of the refractive surgery may force the patient postoperatively into a psychological corner, immobilizing him/her and restricting his/her options. Conclusions: High-tec operations dealing with one of the most elementary senses we have, vision, demand a thorough estimation of the patients profile prior to any surgery. Only matching expectations between the possible and desired outcome and reconfirmation of the match may reduce the risk of postoperative crisis which may carry a risk the patient’s life.

Increased Visual Acuity Will Not Necessarily Equal an Increased Reading Ability in Patients with Subfoveal Neovascular Macular Degeneration

Reading ability in the elderly means independence, and quality of life. In age-related macular degeneration (AMD), the main deficit is the loss of reading ability. The neovascular form is the leading cause of vision loss in the developed world among people over 50 years of age. With ranibizumab (Lucentis) a drug treatment has become available, but, despite good outcome of visual acuity, patients often report that their reading ability has been affected. We aimed therefor to study reading performance with Tobii Eye Tracker in patients, treated with intravitrial Lucentis. Twenty patients, 15 female and 5 male (range 74 - 98 year), were recruited from St. Erik Eye Hospital. All had, before and after treatment, their reading speed, comprehension, fixations, saccadic eye movements measured while reading two texts with an equal readability rating. For all eye movement parameters, except the number of regressions per word, there was no statistically significant difference when comparing the results from before and after treatment. However, a statistically significant increase in the number of regressions per word after treatment as well as increased visual acuity and comprehension, were found. Reading is fundamental in our society and should be tested in order to fully understand a patient’s complaints;however, an increased VA will not necessarily equal an increased reading ability. The results also show that the Tobii system is suitable for evaluation of reading performance in a clinical setting, and can together with other tests, give valuable information about the patients complains and the outcome of a treatment.

Catquest-9SF functioning over a decade–a study from the Swedish National Cataract Register

Background:The Swedish National Cataract Register(NCR)collects data on cataract surgery outcomes during March,including patient-reported outcomes using the Catquest-9SF questionnaire for over 11 years.Previous studies from NCR have shown that the preoperative visual acuity has improved over time.The main purpose of this study was to evaluate the Catquest-9SF Rasch scoring performance in this changing environment.A second purpose was to describe clinical data over the same period for those who completed the questionnaire.Methods:The performance of the Catquest-9SF was analysed by a separate Rasch analysis for each year,resulting in a preoperative and postoperative score for each participating patient in the annual cohorts.The clinical data and questionnaire scoring were analysed for each year in the period 2008-2018 inclusive.Results:Data were available for 42,023 eyes for 11 annual cohorts(2008-2018).The psychometric properties of the questionnaire were stable during the study period.Person separation(precision)for the whole period was 2.58 and varied between 2.45 and 2.72.The person reliability was 0.87 and varied between 0.86 and 0.88.The targeting of question difficulty to person ability became less accurate over time meaning that the item activities became easier to carry out without difficulty.The average targeting for the whole period was−2.06 and changed from−1.92 in 2008 to−2.31 in 2018.The person score improved both before surgery and after surgery,indicating that patients are undergoing surgery at a more able level and getting better outcomes.The average improvement by surgery decreased from 3.41 logits in 2008 to 3.21 logits in 2018(p=0.003).Over time,patient age decreased from 75 to 74 years(p<0.001)and the proportion of women decreased from 63.9 to 57.9%(p<0.001).The mean preoperative visual acuity in both the operated eye and the better eye improved over time(0.47 to 0.40 logMAR,p<0.001 and 0.22 to 0.19 logMAR,p<0.001,respectively),as did the mean postoperative visual acuity in the operated eye(0.14 to 0.09 logMAR,p<0.001).Conclusions:The Catquest-9SF retained stable psychometric properties over this 11-year period although more recent cohorts included slightly younger patients with somewhat better vision.