Different doses of ketamine (10 mg/kg, 20 mg/kg, 30 mg/kg, 40 mg/kg, 50 mg/kg, and 60 mg/kg) were injected i.p. (I.P.), respectively, to male ICR mice to determine the optimal dosage for chronic administration. At and above 40 mg/kg I.P. injection, mice had almost no hindlimb movement during swimming test. Subsequently, 30 mg/kg was used as the dose for the study in the toxicity of long-term ketamine administration on urinary bladder and sperm motility. The treatment group were subdivided into two (n = 10 each group); one received daily ketamine treatment i.p. for 3 months and another group for 6 months. Corresponding number of mice in control groups (n = 5 each group) received saline injection instead of ketamine. Terminal dUTP nick and labeling (TUNEL) study and Sirius red staining were carried out on the sectioned slides of the urinary bladders to study the degree of apoptosis in both epithelium and muscular layers of the urinary bladder and the relative thickness of the muscular layers in this organ was also computed. Apoptosis in the bladder epithelium was observed initially in the 3-month ketamine treated mice and the number of apoptotic cells was significantly different (P < 0.05) between the 3-month and 6-month ketamine treated mice and the control. The relative thickness of muscular layers in the bladder wall also decreased significantly (P < 0.05) when the 6-month treated mice and the control were compared. Sirius red staining revealed increase of collagen in the urinary bladder of the treated mice, most evidently 6 months after ketamine treatment. In addition, the sperm motility was studied and there was a statistically significant difference between the control and ketamine treated groups in the percentages of sperms which were motile (P < 0.05). This suggested that the chronic administration of ketamine affected the genital system as well.

Background/aimsTo determine whether a combination of baseline and change in spectral domain-optical coherence tomography (SD-OCT)-based biomarkers can predict visual outcomes in eyes with diabetic macular oedema (DMO) treated with antivascular endothelial growth factors (VEGF) injections.MethodsThis is a retrospective cohort study conducted in Hong Kong, China. 196 eyes with centre-involving DMO, who received anti-VEGF injections between 1 January 2011 and 30 June 2018 were recruited. Medical records of the participants were retrieved retrospectively, visual acuity (VA) at baseline, 6, 12 and 24 months and SD-OCT before initiation and after completion of anti-VEGF treatment were obtained. The SD-OCT images were evaluated for the morphology of DMO, vitreomacular status, presence of disorganisation of retinal inner layers (DRIL), sizes of intraretinal cysts, visibility of external limiting membrane (ELM), ellipsoid zone (EZ) and cone outer segment tip (COST) and the presence of hyper-reflective foci in retina or the choroid.ResultsThe presence of baseline DRIL, hyper-reflective foci in retina and disruption of ELM/EZ and COST were associated with worse baseline and subsequent VA up to 24 months after treatment. Improvement in DRIL (p=0.048), ELM/EZ (p=0.001) and COST (p=0.002) disruption after treatment was associated with greater improvement in VA at 12 months. Eyes with cystoid macular oedema (p=0.003, OR=8.18) and serous retinal detachment (p=0.011, OR=4.84) morphology were more likely to achieve at least 20% reduction in central subfield thickness.Conclusion and relevanceBaseline SD-OCT biomarkers and their subsequent change predict VA and improvement in vision in eyes with DMO treated with anti-VEGF injections. We proposed an SD-OCT-based system that can be readily used in real-life eye clinics to improve decision making in the management of DMO.

Optical coherence tomography (OCT) is an invaluable imaging tool in detecting and assessing diabetic macular edema (DME). Over the past decade, there have been different proposed OCT-based classification systems for DME. In this review, we present an update of spectraldomain OCT (SDOCT)-based DME classifications over the past 5 years. In addition, we attempt to summarize the proposed OCT qualitative and quantitative parameters from different classification systems in relation to disease severity, risk of progression, and treatment outcome. Although some OCT-based measurements were found to have prognostic value on visual outcome, there has been a lack of consensus or guidelines on which parameters can be reliably used to predict treatment outcomes. We also summarize recent literatures on the prognostic value of these parameters including quantitative measures such as macular thickness or volume, central subfield thickness or foveal thickness, and qualitative features such as the morphology of the vitreoretinal interface, disorganization of retinal inner layers, ellipsoid zone disruption integrity, and hyperreflective foci. In addition, we discuss that a framework to assess the validity of biomarkers for treatment outcome is essentially important in assessing the prognosis before deciding on treatment in DME. Finally, we echo with other experts on the demand for updating the current diabetic retinal disease classification.