Increased Glaucoma Case-finding Through Routine Optical Coherence Tomography in Optometry Practice.

OBJECTIVE: Timely detection of glaucoma is key to preventing or delaying vision loss. This study aimed to assess whether the routine use of optical coherence tomography (OCT) by optometrists for detection of glaucomatous changes in the optic nerve and retina increased glaucoma referrals to ophthalmologists. DESIGN: This study was a retrospective review of routinely-collected electronic medical records of patients from a chain of 331 optometry practices in Australia. PARTICIPANTS: Electronic medical records were reviewed for every patient aged 18-99 years who attended an included practice between January 1 and July 31, 2019. METHODS: Odds of referral for glaucoma assessment were compared between practices performing OCT routinely on all patients (OCT practices, n=175) and without OCT (non-OCT practices, n=20). A subset of referrals were assessed by ophthalmologists to determine the false positive referral rate. MAIN OUTCOME MEASURES: The primary outcome measure of this study was referral to an ophthalmologist for glaucoma assessment. A secondary outcome was the rate of false positive referrals, analysed in a subset of patients referred for glaucoma assessment. RESULTS: Records from 994,461 patients (59% female) were included and 10,475 (1.1%) were referred for glaucoma assessment. Most referrals were associated with normal intraocular pressure (non-OCT practices: n=496, 66%; OCT practices: n=6,603, 68%). Referral for glaucoma was higher in OCT practices (n=9,719, 1.1%) compared to non-OCT practices (n=756, 0.8%, age-, gender- and location-adjusted odds ratio 1.39, 95% confidence interval 1.10-1.76). Of 318 referred patients (3%, all from OCT practices) for whom ophthalmologist feedback was available, 68 (21%) were considered not to have glaucoma. CONCLUSIONS: The routine use of OCT in optometric practice may lead to more timely glaucoma detection and prevention of avoidable vision loss.

Orally administered [¹4C]DPA and [¹4C]DHA are metabolised differently to [¹4C]EPA in rats.

Previous studies have revealed that C20 PUFA are significantly less oxidised to CO2 in whole-body studies compared with SFA, MUFA and C18 PUFA. The present study determined the extent to which three long-chain PUFA, namely 20:5n-3 EPA, 22:5n-3 docosapentaenoic acid (DPA) and 22:6n-3 DHA, were catabolised to CO2 or, conversely, incorporated into tissue lipids. Rats were administered a single oral dose of 2·5 µCi [1-¹4C]DPA, [1-¹4C]EPA, [1-¹4C]DHA or [1-¹4C]oleic acid (18:1n-9; OA), and were placed in a metabolism chamber for 6 h where exhaled ¹4CO2 was trapped and counted for radioactivity. Rats were euthanised after 24 h and tissues were removed for analysis of radioactivity in tissue lipids. The results showed that DPA and DHA were catabolised to CO2 significantly less compared with EPA and OA (P<0·05). The phospholipid (PL) fraction was the most labelled for all three n-3 PUFA compared with OA in all tissues, and there was no difference between C20 and C22 n-3 PUFA in the proportion of label in the PL fraction. The DHA and DPA groups showed significantly more label than the EPA group in both skeletal muscle and heart. In the brain and heart tissue, there was significantly less label in the cholesterol fraction from the C22 n-3 PUFA group compared with the C20 n-3 PUFA group. The higher incorporation of DHA and DPA into the heart and skeletal muscle, compared with EPA, suggests that these C22 n-3 PUFA might play an important role in these tissues.

A short-term n-3 DPA supplementation study in humans.

PURPOSE: Despite the detailed knowledge of the absorption and incorporation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma lipids and red blood cells (RBC) in humans, very little is known about docosapentaenoic acid (DPA, 22:5 n-3). The aim of this study was to investigate the uptake and incorporation of pure DPA and EPA into human plasma and RBC lipids. METHODS: Ten female participants received 8 g of pure DPA or pure EPA in randomized crossover double-blinded manner over a 7-day period. The placebo treatment was olive oil. Blood samples were collected at days zero, four and seven, following which the plasma and RBC were separated and used for the analysis of fatty acids. RESULTS: Supplementation with DPA significantly increased the proportions of DPA in the plasma phospholipids (PL) (by twofold) and triacylglycerol (TAG) fractions (by 2.3-fold, day 4). DPA supplementation also significantly increased the proportions of EPA in TAG (by 3.1-fold, day 4) and cholesterol ester (CE) fractions (by 2.0-fold, day 7) and of DHA in TAG fraction (by 3.1-fold, day 4). DPA proportions in RBC PL did not change following supplementation. Supplementation with EPA significantly increased the proportion of EPA in the plasma CE and PL fractions, (both by 2.7-fold, day 4 and day 7) and in the RBC PL (by 1.9-fold, day 4 and day 7). EPA supplementation did not alter the proportions of DPA or DHA in any lipid fraction. These results showed that within day 4 of supplementation, DPA and EPA demonstrated different and specific incorporation patterns. CONCLUSION: The results of this short-term study suggest that DPA may act as a reservoir of the major long-chain n-3 fatty acids (LC n-3 PUFA) in humans.

Green tea, black tea, and epigallocatechin modify body composition, improve glucose tolerance, and differentially alter metabolic gene expression in rats fed a high-fat diet.

The mechanisms of how tea and epigallocatechin-3-gallate (EGCG) lower body fat are not completely understood. This study investigated long-term administration of green tea (GT), black tea (BT), or isolated EGCG (1 mg/kg per day) on body composition, glucose tolerance, and gene expression related to energy metabolism and lipid homeostasis; it was hypothesized that all treatments would improve the indicators of metabolic syndrome. Rats were fed a 15% fat diet for 6 months from 4 weeks of age and were supplied GT, BT, EGCG, or water. GT and BT reduced body fat, whereas GT and EGCG increased lean mass. At 16 weeks GT, BT, and EGCG improved glucose tolerance. In the liver, GT and BT increased the expression of genes involved in fatty acid synthesis (SREBP-1c, FAS, MCD, ACC) and oxidation (PPAR-alpha, CPT-1, ACO); however, EGCG had no effect. In perirenal fat, genes that mediate adipocyte differentiation were suppressed by GT (Pref-1, C/EBP-beta, and PPAR-gamma) and BT (C/EBP-beta), while decreasing LPL, HSL, and UCP-2 expression; EGCG increased expression of UCP-2 and PPAR-gamma genes. Liver triacylglycerol content was unchanged. The results suggest that GT and BT suppressed adipocyte differentiation and fatty acid uptake into adipose tissue, while increasing fat synthesis and oxidation by the liver, without inducing hepatic fat accumulation. In contrast, EGCG increased markers of thermogenesis and differentiation in adipose tissue, while having no effect on liver or muscle tissues at this dose. These results show novel and separate mechanisms by which tea and EGCG may improve glucose tolerance and support a role for these compounds in obesity prevention.

Angiotensin converting enzyme inhibition lowers body weight and improves glucose tolerance in C57BL/6J mice maintained on a high fat diet.

The renin-angiotensin system (RAS) is functional within adipose tissue and angiotensin II, the active component of RAS, has been implicated in adipose tissue hypertrophy and insulin resistance. In this study, captopril, an angiotensin converting enzyme (ACE) inhibitor that prevents angiotensin II formation, was used to study the development of diet-induced obesity and insulin resistance in obesity prone C57BL/6J mice. The mice were fed a high fat diet (w/w 21% fat) and allowed access to either water or water with captopril added (0.2 mg/ml). Body weight was recorded weekly and water and food intake daily. Glucose tolerance was determined after 11-12 weeks. On completion of the study (after 16 weeks of treatment), the mice were killed and kidney, liver, epididymal fat and extensor digitorum longus muscle (EDL) were weighed. Blood samples were collected and plasma analysed for metabolites and hormones. Captopril treatment decreased body weight in the first 2 weeks of treatment. Food intake of captopril-treated mice was similar to control mice prior to weight loss and was decreased after weight loss. Glucose tolerance was improved in captopril-treated mice. Captopril-treated mice had less epididymal fat than control mice. Relative to body weight, captopril-treated mice had increased EDL weight. Relative to control mice, mice administered captopril had a higher plasma concentration of adiponectin and lower concentrations of leptin and non-esterified fatty acids (NEFA). The results indicate that captopril both induced weight loss and improved insulin sensitivity. Thus, captopril may eventually be used for the treatment of obesity and Type 2 diabetes.

Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance.

In addition to its role in the storage of fat, adipose tissue acts as an endocrine organ, and it contains a functional renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE) plays a key role in the RAS by converting angiotensin I to the bioactive peptide angiotensin II (Ang II). In the present study, the effect of targeting the RAS in body energy homeostasis and glucose tolerance was determined in homozygous mice in which the gene for ACE had been deleted (ACE(-/-)) and compared with wild-type littermates. Compared with wild-type littermates, ACE(-/-) mice had lower body weight and a lower proportion of body fat, especially in the abdomen. ACE(-/-) mice had greater fed-state total energy expenditure (TEE) and resting energy expenditure (REE) than wild-type littermates. There were pronounced increases in gene expression of enzymes related to lipolysis and fatty acid oxidation (lipoprotein lipase, carnitine palmitoyl transferase, long-chain acetyl CoA dehydrogenase) in the liver of ACE(-/-) mice and also lower plasma leptin. In contrast, no differences were detected in daily food intake, activity, fed-state plasma lipids, or proportion of fat excreted in fecal matter. In conclusion, the reduction in ACE activity is associated with a decreased accumulation of body fat, especially in abdominal fat depots. The decreased body fat in ACE(-/-) mice is independent of food intake and appears to be due to a high energy expenditure related to increased metabolism of fatty acids in the liver, with the additional effect of increased glucose tolerance.

Angiotensin converting enzyme inhibition from birth reduces body weight and body fat in Sprague-Dawley rats.

In vitro studies have demonstrated that angiotensin II (ANG II) induces adipocyte hyperplasia and hypertrophy. The aim of the present study was to determine the effect of angiotensin-converting enzyme inhibition on body weight, adiposity and blood pressure in Sprague-Dawley rats. From birth half of the animals (n=15) were given water to drink, while the remainder were administered perindopril in their drinking water (2 mg/kg/day). Food intake, water intake and body weight were measured weekly. Blood pressure was measured by tail cuff plethysmography at 11-weeks. Body fat content and distribution were assessed using dual energy X-ray absorptiometry and Magnetic Resonance Imaging at 12 weeks. Animals administered with perindopril had a body fat proportion that was half that of controls. This was consistent with, but disproportionately greater than the observed differences in food intake and body weight. Perindopril treatment completely removed hypertension. We conclude that the chronic inhibition of ANG II synthesis from birth specifically reduces the development of adiposity in the rat.

Bronchiectasis in Central Australia: a young face to an old disease.

BACKGROUND: Bronchiectasis remains a significant cause of morbidity among specific populations world wide, including many indigenous groups. Data on prevalence in Australian adults are lacking. Indigenous children in Central Australia have the highest rates of bronchiectasis in the world. Outcomes for these individuals after they become adults are not currently available. METHODS: We performed a retrospective case review of the presentation and likely aetiology of adult patients presenting to the Alice Springs Hospital with a primary diagnosis of bronchiectasis. RESULTS: Sixty-one patients and 166 admissions were identified. Fifty-nine patients were indigenous (97%). Mean age was 42+/-15 years. Forty-three patients (70%) had past histories notable for recurrent respiratory tract infections. No predisposing factors could be identified in 11 patients (18%). Human T-cell lymphotropic virus type 1 (HTLV-1) serology was positive in 72% of those studied. Eight (13%) patients died during the study period. CONCLUSION: Bronchiectasis remains a significant cause of morbidity and mortality in Central Australia, with notably different patient characteristics and disease aetiology to other published cohorts. Recurrent respiratory infection is the major cause of illness. Associated factors include indigenous ethnicity, HTLV-1 positivity and childhood in a remote region.

Horner syndrome.

Horner syndrome is an uncommon but important clinical entity, representing interruption of the sympathetic pathway to the eye and face. Horner syndrome is almost always diagnosed clinically, though pharmacological testing can be used to confirm the diagnosis. Imaging modalities such as PET, CT and MRI are important components of work-up for patients presenting with acquired Horner syndrome. Our patient's presentation with Horner syndrome unmasked the causative superior sulcus squamous cell carcinoma and a coincidental lower lobe adenocarcinoma. Successful radical treatment of these cancers resulted in complete resolution of the syndrome and disease-free survival at 18 months. We review the anatomy and pathophysiology underlying this and other causes of Horner syndrome.

Sarcoidosis: case report and review.

Sarcoidosis is a granulomatous disorder of uncertain aetiology that can affect almost any organ. Anterior uveitis is a feature of the condition in about 30 per cent of those affected. We describe a patient with sarcoidosis presenting with anterior uveitis and describe a diagnostic approach. Sarcoidosis is a condition that must be considered in patients presenting with symptomatic uveitis, as the underlying disease is serious and usually treatable. The diagnosis of sarcoidosis is aided by an understanding of the pattern of organ involvement and may ultimately require tissue confirmation through biopsy of granulomata, including those found in the ocular adnexa.

Omega 6 to omega 3 fatty acid imbalance early in life leads to persistent reductions in DHA levels in glycerophospholipids in rat hypothalamus even after long-term omega 3 fatty acid repletion.

Failure to provide omega 3 fatty acids in the perinatal period results in alterations in nerve growth factor levels, dopamine production and permanent elevations in blood pressure. The present study investigated whether changes in brain (i.e., hypothalamus) glycerophospholipid fatty acid profiles induced by a diet rich in omega 6 fatty acids and very low in alpha-linolenic acid (ALA) during pregnancy and the perinatal period could be reversed by subsequent feeding of a diet containing ALA. Female rats (6 per group) were mated and fed either a low ALA diet or a control diet containing ALA throughout pregnancy and until weaning of the pups at 3 weeks. At weaning, the pups (20 per group) remained on the diet of their mothers until 9 weeks, when half the pups were switched onto the other diet, thus generating four groups of animals. At 33 weeks, pups were killed, the hypothalamus dissected from the male rats and analysed for glycerophospholipid fatty acids. In the animals fed the diet with very little ALA and then re-fed the control diet containing high levels of ALA for 24 weeks, the DHA levels were still significantly less than the control values in PE, PS and PI fractions, by 9%, 18% and 34%, respectively. In this group, but not in the other dietary groups, ALA was detected in all glycerophospholipid classes at 0.2-1.7% of the total fatty acids. The results suggest that omega 6-3 PUFA imbalance early in life leads to irreversible changes in hypothalamic composition. The increased ALA and reduced DHA proportions in the animals re-fed ALA in later life are consistent with a dysfunction or down-regulation of the conversion of ALA to 18:4n-3 by the delta-6 desaturase.

Perinatal omega-3 polyunsaturated fatty acid supply modifies brain zinc homeostasis during adulthood.

Dietary omega-3 polyunsaturated fatty acid (PUFA) influences the expression of a number of genes in the brain. Zinc transporter (ZnT) 3 has been identified as a putative transporter of zinc into synaptic vesicles of neurons and is found in brain areas such as hippocampus and cortex. Neuronal zinc is involved in the formation of amyloid plaques, a major characteristic of Alzheimer's disease. The present study evaluated the influence of dietary omega-3 PUFA on the expression of the ZnT3 gene in the brains of adult male Sprague-Dawley rats. The rats were raised and/or maintained on a control (CON) diet that contained omega-3 PUFA or a diet deficient (DEF) in omega-3 PUFA. ZnT3 gene expression was analyzed by using real-time PCR, free zinc in brain tissue was determined by zinquin staining, and total zinc concentrations in plasma and cerebrospinal fluid were determined by atomic absorption spectrophotometry. Compared with CON-raised animals, DEF-raised animals had increased expression of ZnT3 in the brain that was associated with an increased level of free zinc in the hippocampus. In addition, compared with CON-raised animals, DEF-raised animals had decreased plasma zinc level. No difference in cerebrospinal fluid zinc level was observed. The results suggest that overexpression of ZnT3 due to a perinatal omega-3 PUFA deficiency caused abnormal zinc metabolism in the brain. Conceivably, the influence of dietary omega-3 PUFA on brain zinc metabolism could explain the observation made in population studies that the consumption of fish is associated with a reduced risk of dementia and Alzheimer's disease.

Does perinatal omega-3 polyunsaturated fatty acid deficiency increase appetite signaling?

OBJECTIVE: To investigate the effect of maternal dietary omega-3 polyunsaturated fatty acid (PUFA) deficiency and repletion on food appetite signaling. RESEARCH METHODS AND PROCEDURES: Sprague-Dawley rat dams were maintained on diets either supplemented with (CON) or deficient in (DEF) omega-3 PUFA. All offspring were raised on the maternal diet until weaning. After weaning, two groups remained on the respective maternal diet (CON and DEF groups), whereas a third group, born of dams fed the DEF diet, were switched to the CON diet (REC). Experiments on food intake began when the male rats reached 16 weeks of age. Food intake was stimulated either by a period of food restriction, by blocking glucose utilization (by 2-deoxyglucose injection), or by blocking beta-oxidation of fatty acids (by beta-mercaptoacetate injection). RESULTS: DEF animals consumed more than CON animals in response to all stimuli, with the greatest difference (1.9-fold) demonstrated following administration of 2-deoxyglucose. REC animals also consumed more than CON animals in response to food restriction and 2-deoxyglucose but not to beta-mercaptoacetate. DISCUSSION: These findings indicate that supply of omega-3 PUFA, particularly during the perinatal period, plays a role in the normal development of mechanisms controlling food intake, especially glucoprivic (i.e. reduced glucose availability) appetite signaling. Dietary repletion of omega-3 PUFA from 3 weeks of age restored intake responses to fatty acid metabolite signaling but did not reverse those in response to food restriction or glucoprivic stimuli.

Effects of dietary omega-3 polyunsaturated fatty acids on brain gene expression.

Polyunsaturated fatty acids (PUFA) are essential structural components of the central nervous system. Their role in controlling learning and memory has been well documented. A nutrigenomic approach with high-density microarrays was used to reveal brain gene-expression changes in response to different PUFA-enriched diets in rats. In aged rats fed throughout life with PUFA-enriched diets, genes with altered expressions included transthyretin, alpha-synuclein, and calmodulins, which play important roles in synaptic plasticity and learning. The effect of perinatal omega-3 PUFA supply on gene expression later in life also was studied. Several genes showed similar changes in expression in rats fed omega-3-deficient diets in the perinatal period, regardless of whether they or their mothers were fed omega-3 PUFA-sufficient diets after giving birth. In this experiment, among the down-regulated genes were a kainate glutamate receptor and a DEAD-box polypeptide. Among the up-regulated genes were a chemokine-like factor, a tumor necrosis factor receptor, and cytochrome c. The possible involvement of the genes with altered expression attributable to different diets in different brain regions in young and aged rats and the possible mode of regulatory action of PUFA also are discussed. We conclude that PUFA-enriched diets lead to significant changes in expression of several genes in the central nervous tissue, and these effects appear to be mainly independent of their effects on membrane composition. The direct effects of PUFA on transcriptional modulators, the downstream developmentally and tissue-specifically activated elements might be one of the clues to understanding the beneficial effects of the omega-3 PUFA on the nervous system.

Increased blood pressure later in life may be associated with perinatal n-3 fatty acid deficiency.

Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Previous work in both animals and humans with high blood pressure has demonstrated the antihypertensive effects of n-3 polyunsaturated fatty acids (PUFA), although it is not known whether these nutrients are effective in preventing hypertension. The predominant n-3 PUFA in the mammalian nervous system, docosahexaenoic acid (DHA), is deposited into synaptic membranes at a high rate during the perinatal period, and recent observations indicate that the perinatal environment is important for the normal development of blood pressure control. This study investigated the importance of perinatal n-3 PUFA supply in the control of blood pressure in adult Sprague-Dawley rats. Pregnant rat dams were fed semisynthetic diets that were either deficient in (DEF) or supplemented with (CON) n-3 PUFA. Offspring were fed the same diets as their mothers until 9 wk; then, half of the rats from each group were crossed over to the opposite diet creating four groups, i.e., CON-CON; CON-DEF; DEF-DEF, DEF-CON. Mean arterial blood pressures (MAP) were measured directly, at 33 wk of age, by cannulation of the femoral artery. The phospholipid fatty acid profile of the hypothalamic region was determined by capillary gas-liquid chromatography. The tissue phospholipid fatty acid profile reflected the diet that the rats were consuming at the time of testing. Both groups receiving DEF after 9 wk of age (i.e., DEF-DEF and CON-DEF) had similar profiles with a reduction in DHA levels of 30%, compared with rats receiving CON (i.e., CON-CON and DEF-CON). DEF-DEF rats had significantly raised MAP compared with all other groups, with differences as great as 17 mm Hg. DEF-CON rats had raised MAP compared with CON-CON rats, and DEF-DEF rats had higher MAP than CON-DEF rats, despite the fact that their respective fatty acid profiles were not different. These findings indicate that inadequate levels of DHA in the perinatal period are associated with altered blood pressure control in later life. The way in which these long-term effects are produced remains to be elucidated.

Cataract surgery and changes in quality of life measures.

BACKGROUND: This study examines whether quality of life measured with non-disease specific instruments is altered by cataract surgery and whether the effect is modulated by the presence of ocular comorbidity or other non-ocular issues. METHODS: Thirteen patients were assessed pre- and at three months post-cataract surgery. Visual disability was measured with the Visual Disability Assessment. Quality of life was measured using two established generic instruments: the Cantril Ladder and the Profile of Mood States (POMS). Subjects were also asked to report any events that may have influenced their quality of life in the three months after surgery. RESULTS: Visual acuity and visual disability were significantly improved by surgery (p < 0.01). Cantril Ladder score was significantly improved after surgery (p = 0.04). The POMS score improved significantly after surgery, only when cases with ocular comorbidity were excluded (p = 0.04). Two cases had a large deterioration in POMS score that was attributable in one case, to the death of a partner and in the other (a patient with severe glaucoma) to depression from the realisation that there was no further potential for visual improvement. DISCUSSION: Quality of life can be measurably improved by cataract surgery. However, this is less likely if ocular comorbidity is present. The use of generic instruments for outcome studies increases the likely influence of external factors on quality of life measures. Disease specific instruments, such as the Visual Disability Assessment, should be used wherever possible in outcomes research.