A study of olfactory mechanisms

A structure-activity relationship study examining the change in odour quality with systematic variation of alkyl and alkanoate groups of esters (up to C10) has shown that an exposed ester group is necessary for giving esters a fruity smell. Steric hindrance of the ester group results in a minty odour quality becoming predominant. Alkyl haloacetates have been shown to be capable of specifically inhibiting EOG responses in a manner most easily explained by an affinity labelling mechanism. Such compounds may be useful as a means of labelling olfactory receptors so that they may be identified during isolation. Experiments to clarify the role of cyclic AMP in the olfactory transduction mechanism showed that odorant in solution (pentyl acetate) was antagonistic to the effects of SQ 20,009, a potent phosphodiesterase inhibitor. Positive after-potentials to ethanol were stimulated by SQ 20,009, suggesting an alternative mechanism for the effects of cyclic AMP on the EOG response involving increased permeability of the supporting cell membrane to chloride ions. Biochemical studies in olfaction are hampered by the lack of a method for isolating the chemoreceptive membrane. Here experiments have been carried out at the level of the whole tissue using the EOG response to monitor events in the receptor cells. EOG responses, stable over a period of several hours, were obtained from mammalian olfactory epithelium maintained in vitro. Animals such as the sheep and the cow can provide large quantities of tissue that may be necessary for biochemical studies. The preparation described here provides a convenient method of obtaining electro- physiological responses from the olfactory epithelium of such animals

Multi-Modal retinal image analysis via deep learning for the diagnosis of intermediate dry age-related macular degeneration: a feasibility study

Background and Objective. To determine if using a multi-input deep learning approach in the image analysis of optical coherence tomography (OCT), OCT angiography (OCT-A), and colour fundus photographs increases the accuracy of a CNN to diagnose intermediate dry age-related macular degeneration (AMD). Patients and Methods. Seventy-five participants were recruited and divided into three cohorts: young healthy (YH), old healthy (OH), and patients with intermediate dry AMD. Colour fundus photography, OCT, and OCT-A scans were performed. The convolutional neural network (CNN) was trained on multiple image modalities at the same time. Results. The CNN trained using OCT alone showed a diagnostic accuracy of 94%, whilst the OCT-A trained CNN resulted in an accuracy of 91%. When multiple modalities were combined, the CNN accuracy increased to 96% in the AMD cohort. Conclusions. Here we demonstrate that superior diagnostic accuracy can be achieved when deep learning is combined with multimodal image analysis

A multi-centre prospective evaluation of THEIA™ to detect diabetic retinopathy (DR) and diabetic macular oedema (DMO) in the New Zealand screening program

Purpose To validate the potential application of THEIA™ as clinical decision making assistant in a national screening program. Methods A total of 900 patients were recruited from either an urban large eye hospital, or a semi-rural optometrist led screening provider, as they were attending their appointment as part of New Zealand Diabetic Eye Screening Programme. The de-identified images were independently graded by three senior specialists, and final results were aggregated using New Zealand grading scheme, which was then converted to referable/non-referable and Healthy/mild/more than mild/sight threatening categories. Results THEIA™ managed to grade all images obtained during the study. Comparing the adjudicated images from the specialist grading team, “ground truth”, with the grading by the AI platform in detecting “sight threatening” disease, at the patient level THEIA™ achieved 100% imageability, 100% [98.49–100.00%] sensitivity and [97.02–99.16%] specificity, and negative predictive value of 100%. In other words, THEIA™ did not miss any patients with “more than mild” or “sight threatening” disease. The level of agreement between the clinicians and the aggregated results was (k value: 0.9881, 0.9557, and 0.9175), and the level of agreement between THEIA™ and the aggregated labels was (k value: 0.9515). Conclusion This multi-centre prospective trial showed that THEIA™ did not miss referable disease when screening for diabetic retinopathy and maculopathy. It also had a very high level of granularity in reporting the disease level. As THEIA™ has been tested on a variety of cameras, operating in a range of clinics (rural/urban, ophthalmologist-led\optometrist-led), we believe that it will be a suitable addition to a public diabetic screening program

Assessing the accuracy of a large observational registry of neovascular age-related macular degeneration

PURPOSE To evaluate the accuracy of an observational database that tracks real-world treatment outcomes for neovascular age-related macular degeneration. METHODS We audited 245 randomly sampled eyes from 189 patients with 3,356 visits from 11 doctors in the Fight Retinal Blindness! DATABASE Sex, birth year, previous treatments received, treatment, and visual acuity were validated against the clinical notes. Error rates, the proportion of missed visits (the number of visits present in the patient record but not entered into Fight Retinal Blindness!), the level of agreement using Cohen's kappa (κ) and intraclass correlation coefficients, and positive and negative predictive values were calculated. A visual acuity error was defined as an absolute difference of ≥5 letters. RESULTS The overall error rate was 3.5% (95% confidence interval: 3.1-3.9). The error rate for visual acuity was 5.1% (95% confidence interval: 4.2-5.9) and <5% for the remaining fields. The level of agreement for each field ranged from good to excellent (κ or intraclass correlation ≥ 0.75). The positive predictive value and negative predictive value for visits were 99% and 89%, respectively. The proportion of missed visits was 10.2%. CONCLUSION Accuracy of the Fight Retinal Blindness! database was good (>95%). The rate of missed visits was high, possibly due to the high burden of retrospective data entry or patients switching practitioners during treatment

Changes in 12-month outcomes over time for age-related macular degeneration, diabetic macular oedema and retinal vein occlusion

OBJECTIVES To identify whether the outcomes of neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion (RVO) in routine clinical practice have changed over time. METHODS We analysed 12-month outcomes in treatment-naïve eyes that started aflibercept or ranibizumab for nAMD (3802 eyes), DMO (975 eyes), Branch RVO (BRVO, 357 eyes), Central RVO (CRVO, 371 eyes) and Hemi-RVO (HRVO, 54 eyes) from 2015 and 2019 tracked in the prospectively designed observational Fight Retinal Blindness! Registry. RESULTS The mean VA change at 12-month for each year between 2015 and 2019 remained stable or otherwise showed no discernible trends over time in eyes with nAMD (+3.3 to +6 letters), DMO (+3.6 to +6.7 letters) and RVO (+10.3 to +11.7 letters for BRVO, +5.9 to +17.7 letters for CRVO and 10.2 to 20.7 letters for HRVO). The median number of VEGF-inhibitor injections in eyes that completed 12-month follow-up also remained stable at 8-9 for nAMD, 6-7 for DMO, 7-9 for RVO. Fewer eyes (<one-fourth) that started treatment between 2015 and 2018 and more eyes starting in 2019 did not complete 12-month's follow-up visit. The mean VA in non-completers at their last visit was higher than that of their baseline visit. CONCLUSIONS Treatment patterns and outcomes for nAMD, DMO and RVO in routine clinical practice have stabilised over the past 5 years at levels inferior to those reported by the pivotal phase 3 studies. A conscious effort to treat these conditions more intensively, or with longer lasting agents, would likely improve outcomes further in our patients

Incidence, risk factors and outcomes of submacular haemorrhage with loss of vision in neovascular age-related macular degeneration in daily clinical practice: data from the FRB! registry

PURPOSE The main purpose of the study was to report the estimated incidence, cumulative rate, risk factors and outcomes of submacular haemorrhage (SMH) with loss of vision in neovascular age-related macular degeneration (nAMD) receiving intravitreal injections (IVT) of vascular endothelial growth factor (VEGF) inhibitor in routine clinical practice. METHODS Retrospective analysis of treatment-naïve eyes receiving IVTs of VEGF inhibitors (ranibizumab, aflibercept or bevacizumab) for nAMD from 1 January 2010 to 31 December 2020 that were tracked the Fight Retinal Blindness! registry. Estimated incidence, cumulative rate and hazard ratios (HR) of SMH with loss of vision during treatment were measured using the Poisson regression, Kaplan-Meier survival curves and Cox proportional hazard models. RESULTS We identified 7642 eyes (6425 patients) with a total of 135 095 IVT over a 10-year period. One hundred five eyes developed SMH with loss of vision with a rate of 1 per 1283 injections (0.08% 95% confidence interval [95% CI] [0.06; 0.09]). The estimated incidence [95% CI] was 4.6 [3.8; 5.7] SMH with loss of vision per year per 1000 treated patients during the study. The cumulative [95% CI] rate of SMH per patient did not increase significantly with each successive injection (p = 0.947). SMH cases had a mean VA drop of around 6 lines at diagnosis, which then improved moderately to a 4-line loss at 1 year. CONCLUSIONS Submacular haemorrhage (SMH) with loss of vision is an uncommon complication that can occur at any time in eyes treated for nAMD in routine clinical practice, with only limited recovery of vision 1 year later

Three-year treatment outcomes of Aflibercept versus Ranibizumab for diabetic macular edema:: Data from the Fight Retinal Blindness! Registry

PURPOSE Compare the 3-year outcomes of ranibizumab versus aflibercept in eyes with diabetic macular edema in daily practice. METHODS This was a retrospective analysis of naive diabetic macular edema eyes starting intravitreal injections of ranibizumab (0.5 mg) or aflibercept (2 mg) from January 1, 2013 to December 31, 2017 that were collected in the Fight Retinal Blindness! Registry. RESULTS We identified 534 eyes (ranibizumab-267 and aflibercept-267) of 402 patients. The adjusted mean (95% confidence interval) visual acuity change of +1.3 (-0.1 to 4.2) letters in the ranibizumab group and +2.4 (-0.2 to 5.1) letters (P = 0.001) in the aflibercept group at 3 years was not clinically different. However, the adjusted mean CST change seemed to remain significantly different throughout the 3-year period with higher reductions in favor of aflibercept (-87.8 [-108.3 to -67.4] µm for ranibizumab vs. -114.4 [-134.4 to -94.3] for aflibercept; P < 0.01). When baseline visual impairment was moderate (visual acuity ≤68 Early Treatment Diabetic Retinopathy Study letters), we found a faster improvement in visual acuity in eyes treated with aflibercept up until 18 months of treatment than eyes treated with ranibizumab, which then stayed similar until 36 months of treatment, whereas there was no apparent difference when baseline visual impairment was mild (visual acuity ≥69 Early Treatment Diabetic Retinopathy Study letters). The rate of serious adverse events was low. CONCLUSION Aflibercept and ranibizumab were both effective and safe for diabetic macular edema over 3 years

The combination of intravitreal triamcinolone and phacoemulsification surgery in patients with diabeticfoveal oedema and cataract

BACKGROUND: The management of diabetic patients with refractory macular oedema or patients with no adequate pre-operative view to administer laser treatment provide a challenge to the ophthalmologist. We wished to assess the use, safety and effect of intravitreal triamcinolone injection at the time of cataract surgery in patients with diabetic foveal oedema and sight limiting lens opacities. METHOD: This was a longitudinal non-randomised prospective pilot study in 18 eyes (12 patients). All patients had visually significant lens opacities and either persistent diabetic foveal oedema unresponsive to laser treatment-group A, or foveal oedema with no adequate pre-operative view for laser treatment- group B. The cataract surgery was carried out under full aseptic technique using a self-sealing temporal incision and a foldable acrylic lens. Intravitreal triamcinolone was given infratemporally pars plana at the completion of the cataract surgery. The patients were reviewed at day 5, 2 weeks, 2 months and then every 3 months as required. The Wilcoxin matched-pairs test was used to assess the significance of the improvement in visual acuity at 2 months. RESULTS: Twelve patients with a total of 18 eyes were included in the study. There were 10 patients (15 eyes) in group A and 3 patients (3 eyes) in group B. Preoperatively 16 of the 18 eyes had a visual acuity of 6/24 or worse. Postoperatively 83% of patients had completely dry foveae at 2 weeks. Best-corrected visual acuities at two months review ranged from 6/6 to CF with 9 eyes (50%) achieving 6/12 or better (7 eyes (47%) in group A and 2 eyes (67%) in group B). Three eyes had no recorded improvement in visual acuity, but no eyes had deterioration in acuity. The improvement in visual acuity was significant at p = 0.001. There were no significant sight threatening complications. CONCLUSION: Intravitreal triamcinolone has been shown to lead to an improvement in macular oedema and visual improvement in diabetic patients not undergoing cataract surgery but has not, to our knowledge, been previously used in a study like this one. We suggest that intravitreal injection at the time of cataract surgery could be carried out safely with encouraging visual outcomes in patients with diabetic foveal oedema and cataract