THEIA™ development, and testing of artificial intelligence-based primary triage of diabetic retinopathy screening images in New Zealand.

AIM: To develop and evaluate an artificial intelligence triage system with high sensitivity for detecting referable diabetic retinopathy and maculopathy, while maintaining high specificity for non-referable disease, for clinical implementation within the New Zealand national diabetic retinopathy screening programme. METHODS: The THEIA™ artificial intelligence system for retinopathy and maculopathy screening, was developed at Toku Eyes using routinely collected retinal screening datasets from two of the largest district health boards in Auckland, New Zealand: the Auckland District Health Board and the Counties Manukau District Health Board. All retinal images from consecutive individuals receiving retinal screening between January 2009 and December 2018 were used. Images were labelled as non-sight-threatening, potentially referable or sight-threatening for New Zealand implementation, or as referable (potentially referable + sight-threatening)/non-referable (non-sight-threatening) for global comparison. RESULTS: Data from 32 354 unique people with diabetes (63 843 when including multiple visits) were available, of which 95-97%, 0.9-2.4% and 1.1-3.1% were categorized as non-sight-threatening, potentially referable and sight-threatening, respectively. Using the referable/non-referable categories, THEIA achieved overall sensitivity of 94% (95% CI 92-95) in the Auckland District Health Board and 95% (95% CI 92-97) in the Counties Manukau District Health Board datasets, while preserving specificity of 63% (95% CI 62-64) for the Auckland District Health Board and 61% (95% CI 60-62) for the Counties Manukau District Health Board. Implementing THEIA into a New Zealand national diabetic screening programme could significantly reduce the manual grading load. CONCLUSION: THEIA, an artificial intelligence tool to assist in clinical decision-making, tailored to the needs of the New Zealand national diabetic screening programme, delivered high sensitivity for detecting referable retinopathy within the multi-ethnic New Zealand population with diabetes.

A randomized, prospective, blinded comparison of postoperative pain, metabolic response, and perceived health after laparoscopic and small incision cholecystectomy.

BACKGROUND: We have previously shown that in a randomized comparison of laparoscopic (LC) versus small incision (SC) cholecystectomy, postoperative hospital stay is comparable. This randomized prospective study compares the postoperative pain, analgesic and antiemetic consumption, perceived health, and metabolic and respiratory responses after these two procedures. METHODS: Two hundred patients were recruited; postoperative stay, pain scores, analgesic and antiemetic consumption were recorded. Nottingham Health Profile questionnaires were completed by a subgroup of 100 patients, and the metabolic and respiratory responses were also compared in a further subgroup of 20 patients. RESULTS: Pain scores in both groups were low. LC, however, was associated with lower postoperative pain scores and analgesic requirements compared with SC, but the antiemetic requirements were greater after LC. The duration of hospital stay and the perceived health after operation were the same in both groups, and both procedures were associated with a similar reduction of respiratory function. Twenty-four hours after operation the inflammatory (C-reactive protein, CRP) response to LC (22 +/- 20 mg/L) was significantly lower than after SC (68 +/- 30 mg/L), but the neuroendocrine (cortisol) response was similar (LC, 475 +/- 335 nmol/L, compared with SC, 710 +/- 410 nmol/L). Independent of the technique used, the duration of postoperative hospital stay correlated significantly with the magnitude of both the 24-hour postoperative cortisol and CRP responses (cortisol: rs = 0.678, p < 0.001; CRP: rs = 0.566, p = 0.011). CONCLUSIONS: LC appears to be associated with less tissue destruction and pain than SC, but this did not confer any advantage in the degree of postoperative respiratory impairment, length of hospital stay, or postoperative perceived health. The neuroendocrine component of the metabolic response evoked by each procedure was similar and had a significant correlation to patient's postoperative hospital stay. This finding may explain the similar postoperative recovery after LC and SC.

Development of instrumentation to allow the detection of microorganisms using light scattering in combination with surface plasmon resonance.

This paper describes work carried out to develop a biosensor which allows two separate detection principles to operate simultaneously at the same surface. A prototype device was constructed that provided Kretschmann-configuration surface plasmon resonance (SPR) measurement of refractive index (RI) changes using an 820 nm LED light source, whilst a 635 nm diode laser was used to produce light scattering signals from bacterial spores. Both effects occurred at a gold-coated surface. The RI changes were measured conventionally from the side of the gold layer nearer to the light sources. The scattered light was imaged from the opposite face which was in contact with the aqueous sample. Specific detection of bacterial spores through the light scattering mode using antibody capture was investigated. The flow dynamics and interactions with the surface of individual spores were observed. A comparison with SPR for detection using the same antibody/antigen pair was made. Spore suspensions that were readily detectable by light scattering at 10(7) ml(-1) did not provide significant responses by SPR. The potential for future developments is discussed.

Gene probe assays on a fibre-optic evanescent wave biosensor.

This report describes experiments to detect oligonucleotide hybridization at the surface of a fibre-optic evanescent wave biosensor. Conditions were optimized and the time course of hybridization reactions were found to be very rapid compared to conventional hybridization assays. Binding was easily reversed by heating and the sensor surface could be reused many times. Short (16- and 20-mer) oligonucleotides bound to the waveguide surface could be used to detect fluorescein-labelled complementary sequences at the nanomolar level. Polymerase chain reaction was used to generate a 204-base oligomer that was attached to the waveguide surface. Fluorescein-labelled oligos bound at either the proximal or distal ends of this probe were found to give similar outputs.

A prospective, case controlled study of the natural history of diabetic retinopathy and maculopathy after uncomplicated phacoemulsification cataract surgery in patients with type 2 diabetes.

AIM: To determine if uncomplicated phacoemulsification cataract surgery is associated with an accelerated rate of progression of diabetic retinopathy or maculopathy postoperatively. METHODS: A prospective trial of 50 type 2 diabetics undergoing monocular phacoemulsification cataract surgery by a single consultant surgeon. The grade of diabetic retinopathy and diabetic maculopathy in the operated and non-operated fellow eye was assessed preoperatively and for 12 months postoperatively. RESULTS: Overall, retinopathy progression was observed in 11 patients. In seven the retinopathy progressed in both eyes, in three it progressed in the operated eye alone, and in one it progressed in the fellow eye alone. Macular oedema was observed in 13 eyes postoperatively. Four had transient pseudophakic cystoid macular oedema and nine true diabetic maculopathy. Where maculopathy progressed it did so symmetrically in five patients, it progressed in the operated eye alone in four patients, and the fellow eye alone in two patients. There was no significant difference in the number of operated and fellow eyes whose retinopathy or maculopathy progressed postoperatively. In both the operated (OE) and non-operated (NoE) eyes retinopathy progression was associated with a higher mean HbA(1)C (OE p=0.003; NoE p=0.001) and insulin treatment (OE p=0.008, NoE p=0.04). CONCLUSION: Uncomplicated phacoemulsification cataract surgery does not cause acceleration of diabetic retinopathy postoperatively and any progression that is observed probably represents the natural history of the disease. Although macular oedema is common after cataract surgery it may follow a benign course and in many patients the development of clinically significant macular oedema postoperatively probably represents natural disease progression rather than being a direct effect of surgery.

Retinal pigment epithelial changes and choroidal neovascularisation at the edge of posterior staphylomas; a case series and review of the literature.

PURPOSE: To report five myopic patients who presented with a variety of changes at the edge of posterior staphyloma. METHODS: Retrospective, observational case series. The clinical and angiographic records of five patients who showed changes at the edge of posterior staphyloma were reviewed. One of these patients had been referred querying macular dystrophy. RESULTS: On fundus examination, three patients showed retinal pigment epithelial (RPE) changes at the edge of the staphyloma and two showed RPE atrophy with surrounding haemorrhages. Fluorescein angiography revealed areas of hyperfluorescence at the point of change of curvature of the staphyloma suggestive of RPE atrophy in all patients. In two patients, a choroidal neovascular membrane was seen. Indocyanine green angiogram carried out in one patient showed the presence of an occult choroidal neovascular membrane with preservation of the adjacent choriocapillaris. CONCLUSION: This case series illustrates the variety of changes that can occur at the edge of posterior staphylomas, which ranged from RPE disturbance to choroidal neovascular membrane formation. In one of the patients, these changes were mistaken for macular dystrophy. Our observations also support the hypothesis that chorioretinal changes occur at the edge of staphylomas and may predispose to choroidal neovasularisation.

Oral fluorescein angiography with the scanning laser ophthalmoscope in diabetic retinopathy: a case controlled comparison with intravenous fluorescein angiography.

AIM: To compare the performance of oral fundus fluorescein angiography with a confocal scanning laser ophthalmoscope (SLO) with intravenous fundus fluorescein angiography (IVFFA) with a fundus camera in the assessment of sight-threatening diabetic retinopathy. PATIENTS AND METHODS: A total of 25 patients undergoing IVFFA to investigate their diabetic retinopathy were recruited. Participants returned 1 week later and an oral angiogram with the SLO was performed. Six facets of the oral and intravenous angiograms were scored and compared: visualization of the foveal avascular zone (FAZ); branch retinal identification; macular leakage; identification of microaneurysms in areas of macular leakage; peripheral nonperfusion, and leakage from neovascular complexes. RESULTS: Compared to IVFFA, the FAZ was unreliably visualized with oral angiography (Kappa 0.1, 95% CI 0-0.3). In contrast, macular leakage (Kappa 0.78, 95%, CI 0.72-0.83), identification of microaneurysms in areas of macular leakage (Kappa 0.78, 95%, CI 0.72-0.83), and neovascular complexes (Kappa 1.0) were reliably seen. Analysis of the visualization of peripheral nonperfusion was complicated by the finding that profuse dye leakage from neovascular complexes obscured the view of the peripheral retina. If the five angiograms in which this occurred were excluded, oral angiography identified 23 of the 24 eyes in which significant nonperfusion was found on IVFFA. CONCLUSION: Oral angiography with the SLO can provide high-quality angiograms that allow judgments to be made about the presence of treatable diabetic maculopathy, proliferative diabetic retinopathy, and peripheral nonperfusion. In the presence of coexisting macular oedema, it proved to be an unreliable technique with which to investigate foveal ischaemia.

Screening for visual impairment in elderly patients with hip fracture: validating a simple bedside test.

AIMS: 1. To assess the prevalence of visual impairment in those patients who sustain proximal hip fracture after a simple fall. 2. To test the validity of a simple screening test to identify patients with visual impairment. METHODS: Patients on the orthopaedic rehabilitation ward recuperating from proximal hip fracture were recruited. The nurse screener and examining Ophthalmologist independently assessed the patients' distance visual acuity and visual field to confrontation. In addition, the nurse screener assessed for the presence of cataract in the red reflex and the examining Ophthalmologist performed a dilated slit-lamp examination. On completion of the examination, the Ophthalmologist documented the cause(s) of any visual impairment found. RESULTS: A total of 89 patients were assessed. In all, 29 patients (33%) could be classified as visually impaired using the United States criteria and 52 patients (58%) had a distance visual acuity of 6/18 or worse in at least one eye. The test reliably identified those patients with visual impairment (sensitivity 94% (+/-5%), specificity 92% (+/-6%)), but was less reliable at identifying those patients with potentially remedial visual impairment (sensitivity 70% (+/-10%), specificity 92% (+/-6%)). CONCLUSION: The level of visual impairment in this group of patients is high and screening for visual impairment in the elderly with a history of falls is justified. We have demonstrated that a suitably trained member of the rehabilitation team can identify over 94% of those patients with impaired vision. We believe this simple test should now be incorporated into the assessment of all patients requiring rehabilitation after a proximal hip fracture.

Combined strabismus and phacoemulsification cataract surgery: a useful option in selected patients.

PURPOSE: To evaluate the role of combined strabismus and phacoemulsification cataract extraction in patients with symptomatic cataract and strabismus. METHODS: Four procedures of combined strabismus and cataract surgery are described in 3 elderly patients with strabismus of differing aetiologies. Two patients underwent one procedure; the other patient underwent two combined procedures, one to each eye. RESULTS: The visual acuity improved in all 3 patients. Post-operative alignment of the visual axis was achieved which allowed resolution of symptomatic diplopia in patient 1, functional binocular single vision in patient 2 and a noticeably reduced compensatory head posture in patient 3. CONCLUSIONS: Combined strabismus and cataract surgery is a safe procedure that can optimise visual alignment and improve visual acuity with a minimum number of operations.

Peripheral ulcerative keratitis 'corneal melt' and rheumatoid arthritis: a case series.

OBJECTIVES: (1) To review the visual and systemic outcomes of patients who developed rheumatoid arthritis (RA)-associated peripheral ulcerative keratitis (PUK). (2) To describe the clinical and serological characteristics of the patients' arthropathy at the time of presentation of this rare condition. (3) To review the aetiology and management of RA-associated PUK. Patients and methods. A case series is given of all nine patients within our unit who have developed RA-associated PUK since 1996. Details of the patients' arthropathy and the serological characteristics of the RA at presentation of PUK were noted. The patients' visual outcomes and the development of any significant systemic complications were recorded. RESULTS: All patients had long-standing seropositive, erosive RA. PUK was associated with a poor visual outcome in most patients, five requiring emergency corneal surgery to prevent perforation of the globe. Two patients developed systemic vasculitis within 1 month of PUK onset, one of whom died. CONCLUSION: RA-associated PUK often has a poor visual outcome and its appearance may herald the transformation of a patient's RA into the systemic vasculitic phase. RA-associated PUK should be managed with aggressive immunosuppression if the associated morbidity and mortality are to be avoided. Cell-mediated mechanisms appear to be important in the aetiopathogenesis of PUK and a combination of corticosteroids and cyclosporin is therefore probably the regimen of choice.

Autosomal dominant congenital superior oblique palsy.

PURPOSE: We describe a mother and all her offspring with congenital superior oblique palsy (CSOP), and a father and all his sons with unilateral CSOP. We discuss the inheritance pattern in our pedigrees and compare it with previous reports. METHOD: All available family members were examined. The prism cover test was performed. Ocular movements were examined in all positions of gaze and where possible a Hess chart plotted. Lang and TNO stereotests were used to determine the stereo-acuity. The results of these tests combined with the Bielschowsky head tilt test (BHTT) were used to confirm the diagnosis of superior oblique palsy. The condition was classified as congenital if it presented early based on history or the observation of old photographs and in the absence of a causative factor. RESULTS: The affected members of family A consist of a father and his three sons with unilateral CSOP. His daughter had a mild weakness of her left inferior and superior rectus muscle. One of his sons was asymptomatic and only recognised on screening of the family for the study. The affected members of family B consist of a mother and her younger daughter with unilateral CSOP and her older daughter with bilateral CSOP. She had no other children. CONCLUSIONS: Our families demonstrate what is probably an autosomal dominant form of CSOP. It is possible that hereditary CSOP is more common than previously reported.

Improved thermostability of the North American firefly luciferase: saturation mutagenesis at position 354.

We have used random chemical mutagenesis and a simple genetic screen to generate and isolate a thermostable mutant of luciferase from the North American firefly (Photinus pyralis). A single G-to-A transition mutation, resulting in the substitution of a glutamate for a lysine residue at position 354 in the protein sequence, was shown to be responsible for this enhanced thermostability. Replacement of Glu-354 with all possible amino acid residues was achieved using directed mutagenesis, and produced mutant enzymes with a range of thermostabilities. The mutations E354K and E354R conferred the largest increases in thermostability, suggesting that side-chain size and hydrophobicity, as well as charge, may also be important contributors to the overall thermostability of the polypeptide chain at this position. Unusually for such mutations, biochemical studies suggest that this position is on the surface of the protein and exposed to solvent.

Specific assays for bacteria using phage mediated release of adenylate kinase.

A sensitive and rapid assay method for the specific detection of bacteria was developed using Escherichia coli and Salmonella newport as the test organisms. Bacteriophages were used to provide specific lysis of the bacteria and then the release of cell contents was measured by ATP bioluminescence. Increased sensitivity was obtained by focusing on the bacteria's adenylate kinase (AK) as the cell marker instead of ATP as conventionally used. Fewer than 10(3) E. coli cells could be readily detected in less than 1 h. Salmonella newport assays, although as sensitive, were slower and took up to 2 h. The effects of the culture medium, the phage, and the presence of non-specific bacteria were examined.

A prospective evaluation of the Heidelberg retina flowmeter in diagnosing ischaemia following branch retinal vein occlusion: a masked, controlled comparison with fluorescein angiography.

PURPOSE: To evaluate the use of the Heidelberg retina flowmeter (HRF) in diagnosing retinal ischaemia following macular branch retinal vein occlusion. METHODS: Ten patients with ischaemic macular branch retinal vein occlusion, as determined by strict fluorescein angiographic criteria, were examined with the HRF. Blood flow, blood volume and blood velocity characteristics from areas of ischaemic and non-ischaemic retina were recorded and the results between the normal and ischaemic areas of retina compared with paired t-test analysis. Ten healthy volunteers were similarly examined and acted as a control group. RESULTS: Compared with normal retina the HRF recorded a statistically significant reduction in blood flow within the ischaemic retina in 7 of the 10 study patients. In 2 patients the HRF actually recorded a statistically significant increase in blood flow in the area of ischaemic retina; there was no significant difference in the blood flow recorded in the normal and ischaemic retina in the remaining patient. HRF examination of the control group revealed a significant difference in the blood flow between two areas of apparently normal retina in 3 of the 10 volunteers. CONCLUSION: The HRF is not a reliable tool for diagnosing retinal ischaemia following branch retinal vein occlusion. Our results may suggest that the HRF blood flow recordings are not derived from the retinal circulation alone, but represent the cumulative blood flow through the combined circulations of the retina and choriocapillaris.