The Effect of Macular Hole Duration on Surgical Outcomes: An Individual Participant Data Study of Randomized Controlled Trials

Topic: To define the effect of symptom duration on outcomes in people undergoing surgery for idiopathic full-thickness macular holes (iFTMHs) by means of an individual participant data (IPD) study of randomized controlled trials (RCTs). The outcomes assessed were primary iFTMH closure and postoperative best-corrected visual acuity (BCVA). Clinical Relevance: Idiopathic full-thickness macular holes are visually disabling with a prevalence of up to 0.5%. Untreated BCVA is typically reduced to 20/200. Surgery can close holes and improve vision. Symptom duration is thought to affect outcomes with surgery, but the effect is unclear. Methods: A systematic review identified eligible RCTs that included adults with iFTMH undergoing vitrectomy with gas tamponade in which symptom duration, primary iFTMH closure, and postoperative BCVA were recorded. Bibliographic databases were searched for articles published between 2000 and 2020. Individual participant data were requested from eligible studies. Results: Twenty eligible RCTs were identified. Data were requested from all studies and obtained from 12, representing 940 eyes in total. Median symptom duration was 6 months (interquartile range, 3–10). Primary closure was achieved in 81.5% of eyes. There was a linear relationship between predicted probability of closure and symptom duration. Multilevel logistic regression showed each additional month of duration was associated with 0.965 times lower odds of closure (95% confidence interval [CI], 0.935–0.996, P = 0.026). Internal limiting membrane (ILM) peeling, ILM flap use, better preoperative BCVA, face-down positioning, and smaller iFTMH size were associated with increased odds of primary closure. Median postoperative BCVA in eyes achieving primary closure was 0.48 logarithm of the minimum angle of resolution (logMAR) (20/60). Multilevel logistic regression showed for eyes achieving primary iFTMH closure, each additional month of symptom duration was associated with worsening BCVA by 0.008 logMAR units (95% CI, 0.005–0.011, P < 0.001) (i.e., ∼1 Early Treatment Diabetic Retinopathy Study letter loss per 2 months). ILM flaps, intraocular tamponade using long-acting gas, better preoperative BCVA, smaller iFTMH size, and phakic status were also associated with improved postoperative BCVA. Conclusions: Symptom duration was independently associated with both anatomic and visual outcomes in persons undergoing surgery for iFTMH. Time to surgery should be minimized and care pathways designed to enable this

Akutna oralna toksičnost organofosfornih insekticida i inhibicija kolinesteraza u pilića

Acute toxic effects of three commonly used insecticidal preparations of the organophosphates chlorpyrifos, diazinon, and dichlorvos were examined in mixed breed broiler chicks, and cholinesterase activity in plasma and brain were measured. The acute (24 h) oral median lethal doses (LD50) of chlorpyrifos, diazinon, and dichlorvos were 10.79 mg kg-1, 6.32 mg kg-1, and 6.30 mg kg-1, respectively, as determined by the up-and-down method in chicks. Signs of cholinergic toxicosis in the chicks appeared within two hours after dosing, and they included salivation, lacrimation, gasping, frequent defecation, drooping of wings, tremors, convulsions, and recumbency before death. Halving the oral LD50 of chlorpyrifos (5 mg kg-1), diazinon (3 mg kg-1), and dichlorvos (3 mg kg-1) caused immobility and wing drooping, but not the clinical signs of cholinergic toxicity. However, at full LD50 doses of these insecticides, chicks showed clinical signs of cholinergic toxicity similar to those seen in the LD50 experiments. Two out of six chicks died within two hours after treatment with LD50 doses of chlorpyrifos and dichlorvos, whereas LD50 dosing with diazinon caused death in three out of six chicks. Compared to control values, the insecticides reduced plasma and whole brain cholinesterase activities by 29 % to 84 % and 18 % to 77 %, respectively, depending on the dose. The decrease in plasma cholinesterase correlated well (r = 0.82) with that of the brain. These data suggest that organophosphate insecticides administered orally at LD50 doses induce clinical signs of cholinergic poisoning and concurrently reduce brain and plasma cholinesterase activities in chicks.Ispitano je akutno toksično djelovanje triju često rabljenih organofosfornih insekticida klorpirifosa, diazinona i diklorvosa u brojlera te je izmjerena aktivnost kolinesteraza u njihovoj plazmi i mozgu. Srednja letalna doza LD50 klorpirifosa iznosila je 10,79 mg kg-1, diazinona 6,32 mg kg-1 te diklorvosa 6,30 mg kg-1. Prvi su se znakovi kolinergičkoga sindroma u pilića javili unutar dva sata od oralne primjene, a obuhvaćali su slinjenje, suženje, teško disanje, učestalu defekaciju, obješena krila, drhtavicu, grčenje i nesposobnost stajanja uoči smrti. Oralna primjena polovice srednje letalne doze insekticida klorpirifosa (5 mg kg-1), diazinona (3 mg kg-1) i diklorvosa (3 mg kg-1) dovela je do nepokretnosti i obješenih krila, ali bez kliničkih znakova kolinergičke toksičnosti koji su uočeni kod pokusa radi utvrđivanja srednje letalne doze (LD50). Međutim, doze ovih insekticida koje su odgovarale LD50, dovele su do kliničkih znakova kolinergičke toksičnosti sličnih onima zamijećenim kod utvrđivanja LD50. Dva od šest pilića uginula su unutar dva sata od primjene bilo klorpirifosa bilo diklorvosa u dozama koje su odgovarale LD50, dok je diazinon u odgovarajućoj srednjoj letalnoj dozi uzrokovao smrt triju od šest pilića. U odnosu na kontrolne vrijednosti, insekticidi su doveli do smanjenja aktivnosti kolinesteraze koja je ovisila o dozi, a kretala se od 29 % do 84 % u plazmi te od 18 % do 77 % u mozgu. Pad aktivnosti kolinesteraze u plazmi dobro je korelirao s njezinim padom u mozgu (r=0,82). Ovi podaci upućuju na to da oralna primjena organofosfornih insekticida u dozama koje odgovaraju srednjoj letalnoj dozi dovode do znakova kolinergičkoga trovanja u pilića te do istodobnoga pada aktivnosti kolinesteraza u mozgu i plazmi

Akutna toksičnost veterinarskih i poljoprivrednih formulacija organofosfata diklorvosa i diazinona u pilića

Formulation components of organophosphate insecticidal preparations might affect their toxic action in animals. The objective of this study was to examine and compare the acute toxicity and cholinesterase inhibition in seven to 14-day-old chicks dosed orally with dichlorvos and diazinon in standard veterinary and agricultural formulations. The acute (24 h) oral median lethal doses (LD50) of the formulations were determined using the up-and-down method. Respective LD50 of dichlorvos of the veterinary and agricultural formulations in chicks were 11.1 mg kg-1 and 6.51 mg kg-1 and those of diazinon 6.4 mg kg-1 and 6.7 mg kg-1. Plasma and brain cholinesterase activities were measured by electrometry after in vivo and in vitro exposure to organophosphates. The chicks showed signs of cholinergic toxicosis within one hour of dosing. Dichlorvos (8 mg kg-1) and diazinon (4 mg kg-1) in the veterinary and agricultural formulation signifi cantly reduced both plasma and brain cholinesterase activities in the chicks. The veterinary formulation of dichlorvos reduced plasma ChE by 60 % and agricultural by 40 % and brain ChE by 93 % and 87 %, respectively. In contrast, ChE inhibition by diazinon in the agricultural formulation of diazinon was stronger than by the veterinary formulation; 72 % vs. 64 % in plasma and 97 % vs. 80 % in the brain, respectively. The highest in vitro inhibitions were observed with dichlorvos in the agricultural formulation (50 %) in the brain samples and with diazinon in the agricultural formulation (52 %) in the plasma samples. While they exist, differences between formulations cannot be taken as a rule and further investigations should inventory the toxicity of standard veterinary and agricultural organophosphate formulations in addition to the known data for pure forms.Sastojci formulacija mogu djelovati na toksičnost organofosfatnih insekticidnih pripravaka u životinja. Cilj je ovog istraživanja bio ispitati i usporediti akutnu inhibiciju kolinesteraza u pilića starih 7 do 14 dana koji su na usta primili organofosfatne insekticide diklorvos i diazinon u odgovarajućim formulacijama za veterinarsku odnosno poljoprivrednu primjenu. Dvadesetčetverosatna akutna letalna doza (LD50) diklorvosa bila je 11,1 mg kg-1 u veterinarskim odnosno 6,51 mg kg-1 u poljoprivrednim formulacijama, a diazinona 6,4 mg kg-1 odnosno 6,7 mg kg-1. Do kolinergičke toksikoze u pilića došlo je jedan sat nakon primjene. Nakon izlaganja organofosfatima in vivo i in vitro izmjerena je aktivnost kolinesteraza u plazmi i mozgu s pomoću elektrometrije. Oralne doze diklorvosa (8 mg kg-1) odnosno diazinona (4 mg kg-1) putem veterinarskih odnosno poljoprivrednih formulacija značajno su smanjile aktivnost kolinesteraza u plazmi i mozgu pilića. In vitro su također oba organofosfata inhibirala aktivnost kolinesteraza, bez obzira na formulaciju. Poljoprivredna formulacija diklorvosa izazvala je najjaču inhibiciju (50 %) u mozgu pilića, dok je poljoprivredna formulacija diazinona najjače inhibirala (52 %) aktivnost u plazmi. Ovo istraživanje pokazuje da različite formulacije organofosfatnih insekticida mogu dovesti do različita otrovanja i različito djelovati na kolinesteraznu aktivnost u mozgu i plazmi

Plasma and whole brain cholinesterase activities in three wild bird species in Mosul, IRAQ: In vitro inhibition by insecticides

Plasma and brain cholinesterase activities were determined in three wild bird species to assess their exposure to organophosphate and carbamate insecticides which are used in agriculture and public health. In the present study, we used an electrometric method for measurement of cholinesterase activities in the plasma and whole brain of three indigenous wild birds commonly found in northern Iraq. The birds used were apparently healthy adults of both sexes (8 birds/species, comprising 3–5 from each sex) of quail (Coturnix coturnix), collard dove (Streptopelia decaocto) and rock dove (Columba livia gaddi), which were captured in Mosul, Iraq. The mean respective cholinesterase activities (Δ pH/30 minutes) in the plasma and whole brain of the birds were as follows: quail (0.96 and 0.29), collard dove (0.97and 0.82) and rock dove (1.44 and 1.42). We examined the potential susceptibility of the plasma or whole brain cholinesterases to inhibition by selected insecticides. The technique of in vitro cholinesterase inhibition for 10 minutes by the organophosphate insecticides dichlorvos, malathion and monocrotophos (0.5 and 1.0 µM) and the carbamate insecticide carbaryl (5 and10 µM) in the enzyme reaction mixtures showed significant inhibition of plasma and whole brain cholinesterase activities to various extents. The data further support and add to the reported cholinesterase activities determined electrometrically in wild birds in northern Iraq. The plasma and whole brain cholinesterases of the birds are highly susceptible to inhibition by organophosphate and carbamate insecticides as determined by the described electrometric method, and the results further suggest the usefulness of the method in biomonitoring wild bird cholinesterases