Retinal oxygen saturation is associated with HbA1c but not with short-term diabetes control, internal environment, smoking and mild retinopathy - ROXINEGLYD study.

PURPOSE: Purpose of this prospective uncontrolled single-centre pilot study was to find an association of retinal oxygen saturation (SatO2 ) with acid-base balance (ABB), carboxyhaemoglobin concentration, current plasma glucose concentration (PG), mean PG and PG variability over the last 72 hr, haemoglobin A1c (HbA1c), and other conditions. METHODS: Forty-one adults (17 men) with type 1 (N = 14) or type 2 (N = 27) diabetes mellitus, age 48.6 ± 13.5 years, diabetes duration 9 (0.1-36) years, BMI 29.4 ± 6.3 kg/m2 , and HbA1c 52 ± 12.7 mmol/mol completed the study. The 4-day study comprised two visits (Day l, Day 4) including 72 hr of continuous glucose monitoring (CGM) by iPro® 2 Professional CGM (Medtronic, MiniMed, Inc., Northridge, CA, USA). Retinal oximeter Oxymap T1 (Oxymap ehf., Reykjavik, Iceland) was used to assess SatO2 . RESULTS: Wilcoxon signed-rank test showed no SatO2 difference between eyes and visits. Spearman's correlation analysis revealed a significant correlation between arterial SatO2 and PG variability in type 2 diabetes mellitus, a positive correlation of venous SatO2 with HbA1c and with finger pulse oximetry. However, no correlation of SatO2 with ABB, carboxyhaemoglobin, current PG, mean PG over the 72 hr, age, diabetes duration, BMI, lipoproteinaemia, body temperature, systolic and diastolic blood pressure, heart rate, central retinal thickness and retinal nerve fibre layer thickness was found. CONCLUSION: This study confirmed the association of venous SatO2 with long-term but not with short-term diabetes control, ABB and other conditions. The increased SatO2 and questionable impact of PG variability on retinal SatO2 is a research challenge.

Retinopathy in patient with AC hemoglobinopathy / Retinopatia em pacientes com hemoglobinopatia AC

Abstract Hemoglobin C is the second most frequent Hb variant in Brazil and the world. Hemoglobin C trait is described as a benign and asymptomatic condition. There is little information in the literature about the association of retinal vascular disease and the presence of hemoglobin AC, being this information restricted to a few case reports. This case report describes a 26-year-old female patient with hemoglobin C trait. She presents areas of non-perfusion and arteriovenous shunts in the retinal temporal periphery of the left eye, like changes in Goldberg's stage II of proliferative sickle retinopathy. After three years of follow-up, the patient exhibits the same the alteration in right eye as well.

Resumo A hemoglobina C é a segunda variante de hemoglobina mais comum no Brasil e no mundo. O traço C é descrito como uma condição benigna e assintomática. Há pouca informação na literatura sobre a associação de doença vascular retiniana e a presença de hemoglobina AC, sendo esta informação restrita a alguns poucos relatos de casos. Este relato de caso descreve uma paciente do gênero feminino de 26 anos de idade com traço C. Ela apresenta áreas de não perfusão e shunts artério-venosos na periferia temporal da retina do olho esquerdo, similar ao estágio II de Goldberg de retinopatia proliferativa falciforme. Após três anos de acompanhamento, a paciente apresentou a mesma alteração também em olho direito.

Detection of serum anti-retinal antibodies in the Chinese patients with presumed autoimmune retinopathy.

PURPOSE: To explore the presence of serum anti-retinal antibodies (ARAs) in the Chinese patients with presumed autoimmune retinopathy (AIR). METHODS: Twenty-three Chinese patients with presumed AIR, disease controls including 40 RP patients, 22 bilateral uveitis patients, 18 acute zonal outer occult retinopathy (AZOOR) patients, and 30 healthy donors were included. Serum samples of all the subjects were obtained and analyzed for the presence of four ARAs including recoverin, α-enolase, carbonic anhydraseII (CAII), and collapsin response-mediated protein (CRMP)-5 by Western bolt assay. RESULTS: ARAs were present in the serum of either presumed AIR patients, disease control, or healthy donors. One or more ARAs were present in the 78.2% of presumed AIR while they were indicated in the 35.0% of RP patients (p < 0.01) and 33.3% of healthy donors (p < 0.01). The prevalence of ARAs in the bilateral uveitis and AZOOR was 63.3% and 100% respectively. Positive rate of α-enolase antibody present in the presumed AIR, disease control, and healthy donors was 73.9%, 47.5%, and 33.3% respectively. Positive rate of CAII antibody present above groups was 52.1%, 50%, and 33.3% respectively. Recoverin antibody seemed to be specifically present in the serum of patients with cancer-associated retinopathy. CONCLUSION: Presence of serum ARAs including recoverin, α-enolase, CAII, or CRMP-5 in the Chinese patients with presumed AIR occurred significantly more often than RP patients and healthy donors. Seropositivity of ARAs had diagnostic value for the presumed AIR but mere presence was not sufficient for the diagnosis due to identification of them in the healthy controls and other retinal diseases.

The impact of IGF-I, puberty and obesity on early retinopathy in children: a cross-sectional study.

BACKGROUND: Childhood obesity has been correlated with coronary heart disease, but the correlation with microvascular disease remains unclear. The retinal microcirculation is affected early in the process of atherosclerosis and it offers the opportunity to indirectly study the effects of obesity on small brain vessels. Insulin-like growth factor 1 (IGF-I) is involved in angiogenesis and it has a crucial role in retinal vascularization. METHODS: A single-centre cross-sectional study was performed in 268 children and adolescents (116 males; mean age 13.03 ± 1.9 years,) with overweight/obesity, in order to identify risk factors for early retinopathy. RESULTS: Nine patients (3.3%) showed signs of retinopathy, defined as arteriovenous crossings and/or papilledema. Body mass index and fat mass, analysed by Dual X-ray Absorptiometry, were not different in patients with or without retinopathy. Patients with retinopathy were pubertal and showed higher waist circumference (107.78 ± 15.83 versus 99.46 ± 10.85 cm; p: 0.027), waist circumference/height ratio (0.66 ± 0.07 versus 0.62 ± 0.05; p: 0.04) and IGF-I SDS (0.03 ± 1.3 versus - 0.66 ± 0.9; p: 0.04). Multivariate analysis (after correction for sex, age, family history of type 2 diabetes mellitus, obesity, cardiovascular disease, hypertension and dyslipidaemia) showed that waist circumference/height ratio and IGF-I SDS were the only variables independently correlated with the presence of retinopathy. CONCLUSIONS: Retinal vascular changes may become evident as an early complication of overweight and obesity, even during childhood and adolescence. Relatively high levels of IGF-I during this phase may act as an additional risk factor for microvascular damage. The screening for retinopathy should be proposed to all children and adolescents with overweight/obesity.

Anti-angiogenic effects of valproic acid in a mouse model of oxygen-induced retinopathy.

Pathological retinal angiogenesis contributes to the pathogenesis of several ocular diseases. Valproic acid, a widely used antiepileptic drug, exerts anti-angiogenic effects by inhibiting histone deacetylase (HDAC). Herein, we investigated the effects of valproic acid and vorinostat, a HDAC inhibitor, on pathological retinal angiogenesis in mice with oxygen-induced retinopathy (OIR). OIR was induced in neonatal mice by exposure to 80% oxygen from postnatal day (P) 7 to P10 and to atmospheric oxygen from P10 to P15. Mice were subcutaneously injected with valproic acid, vorinostat, or vehicle once a day from P10 to P14. At P15, retinal neovascular tufts and vascular growth in the central avascular zone were observed in mice with OIR. Additionally, immunoreactivity for phosphorylated ribosomal protein S6 (pS6), an indicator of mammalian target of rapamycin (mTOR) activity, was detected in the neovascular tufts. Both valproic acid and vorinostat reduced the formation of retinal neovascular tuft without affecting vascular growth in the central avascular zone. Valproic acid reduced the pS6 immunoreactivity in neovascular tufts. Given that vascular endothelial growth factor (VEGF) activates mTOR-dependent pathways in proliferating endothelial cells of the neonatal mouse retina, these results suggest that valproic acid suppresses pathological retinal angiogenesis by interrupting VEGF-mTOR pathways.

Anomalous coagulation factors in non-arteritic anterior ischemic optic neuropathy with central retinal vein occlusion: A case report.

RATIONALE: Non-arteritic anterior ischemic optic neuropathy (NAION) is characterized by sudden, painless visual loss and optic disc edema. NAION occurs mainly in the presence of cardiovascular disease and hypercoagulability, mainly in patients over 50 years of age. We experienced a case of NAION associated with central retinal vein occlusion (CRVO) in a young man with no underlying disease. PATIENT CONCERNS: A 46-year-old man was referred to our clinic following a sudden loss of vision in his right eye. The patient exhibited no underlying disease and reported no ongoing medication. Significant visual loss and visual disturbance of the right eye were observed. The pupil of the right eye was enlarged and an afferent pupillary defect was observed. On fundus examination, retinal hemorrhage was observed in the peripheral retina; macular edema was observed in optical coherence tomography analysis. However, optic disc edema was not evident. No abnormal findings were found in routine blood tests for hypercoagulability. After 3 days of steroid intravenous injection, macular edema disappeared and visual acuity was improved, but optic disc edema began to appear. One week later, optic disc edema was evident and visual acuity was significantly reduced; thus, the patient was diagnosed with NAION. In fluorescein angiography, peripheral retinal ischemia was observed, suggesting that CRVO was complicated. Blood tests, including analysis of coagulation factors, were performed again, showing that coagulation factors IX and XI were increased. DIAGNOSES: Anomalous coagulation factors in non-arteritic anterior ischemic optic neuropathy with central retinal vein occlusion. INTERVENTIONS: Systemic steroids were administered. OUTCOMES: One month later, optic disc edema and retinal hemorrhage gradually diminished and eventually disappeared; however, visual acuity did not recover. CONCLUSION: In young patients without underlying disease, cases of NAION require careful screening for coagulation disorders. Even if there is no abnormality in the test for routine coagulation status, it may be necessary to confirm a coagulation defect through an additional coagulation factor assay.

Antiplatelet and anticoagulant agents in vitreoretinal surgery: a prospective multicenter study involving 804 patients.

PURPOSE: To assess the rate of hemorrhagic complications after vitreoretinal surgery and the influence of antithrombotic agents. METHODS: Hemorrhagic complications of vitreoretinal procedures performed in seven ophthalmologic centers on patients treated or not treated with antiplatelet (AP) or anticoagulant (AC) agents were prospectively collected. Patients' characteristics, surgical techniques, and complications were recorded during surgery and for 1 month after. RESULTS: Eight hundred four procedures were performed between January 2015 and April 2015. Among them, 18.4% were treated with AP agents (n = 148) and 7.8% with AC agents (n = 63), with 18 of them treated with NOACS (new oral anticoagulants). AP or AC agents were continued in 96.5% and 80.7% of cases, respectively. Fifty-three patients (6.6%) developed one or more hemorrhagic complications in one eye during this period. In univariate analysis, AC agents were not associated with hemorrhagic complications (P = 0.329) in contrast to AP (P = 0.005). However, in multivariate analysis, AP agents were no longer associated with hemorrhagic complications and the intraoperative use of endodiathermy was the only factor associated with hemorrhagic complications (P = 0.001). CONCLUSIONS: This study showed that AP and AC agents were not a factor associated with hemorrhagic complications during vitreoretinal surgery. The continuation of these treatments should be considered without risk of severe hemorrhagic complications.

Elevated serum levels of IL-6 and CXCL9 in autoimmune retinopathy (AIR) patients.

Autoimmune retinopathy (AIR) is a rare immune-mediated retinopathy associated with circulating antiretinal antibodies (ARAs). Other prominent features of AIR include visual field deficits and photoreceptor dysfunction in the setting of progressive unexplained vision loss. The role of inflammation is poorly understood in AIR. Since cytokines play a central role in the initiation and development of inflammation, we evaluated the presence of proinflammatory cytokines and chemokines in AIR patient sera. We demonstrate that IL-6 and CXCL9 are both elevated in AIR patient sera. Moreover, the presence and concentration of these 2 molecules appear to correlate with AIR patient disease severity. This cytokine profile, IL-6 and CXCL9, has been described to participate in a variety of autoimmune and inflammatory diseases. Our study provides support for an activated inflammatory process in AIR and identifies possible mechanisms that can drive autoimmunity in this disease.

Repurposing propranolol as a drug for the treatment of retinal haemangioblastomas in von Hippel-Lindau disease.

BACKGROUND: Von Hippel-Lindau (VHL) disease is a rare oncological disease with an incidence of 1:36,000, and is characterized by the growth of different types of tumours. Haemangioblastomas in the central nervous system (CNS) and retina, renal carcinoma and pheochromocytomas are the most common tumours. The absence of treatment for VHL leads to the need of repeated surgeries as the only option for these patients. Targeting VHL-derived tumours with drugs with reduced side effects is urgent to avoid repeated CNS surgeries. Recent reports have demonstrated that propranolol, a ß-blocker used for the treatment of hypertension and other cardiac and neurological diseases, is the best option for infantile hemangioma (IH). Propranolol could be an efficient treatment to control haemangioblastoma growth in VHL disease given its antiangiogenic effects that were recently demonstrated by us. The main objective of the present study was the assessment of the efficacy and safety of propranolol on retinal haemangioblastoma in von Hippel-Lindau disease (VHL). METHODS: 7 VHL patients, from different regions of Spain, affected from juxtapapillary or peripheral haemangioblastomas were administered 120 mg propranolol daily. Patients were evaluated every 3 months for 12 months, at Virgen de la Salud Hospital (Toledo). The patients had juxtapapillary or peripheral haemangioblastomas but had refused standard treatments. RESULTS: Propranolol was initiated with a progressive increase up to a final dose of 120 mg daily. All tumours remained stable, and no new tumours appeared. The reabsorption of retinal exudation was noted in the two patients having exudates. No adverse effects were recorded. VEGF and miRNA 210 levels were monitored in the plasma of patients as possible biomarkers of VHL. These levels decreased in all cases from the first month of treatment. CONCLUSIONS: Although more studies are necessary, the results of this work suggest that propranolol is a drug to be considered in the treatment of VHL patients with retinal haemangioblastomas. VEGF and miRNA 210 could be used as biomarkers of the VHL disease activity. TRIAL REGISTRATION: The study has a clinical trial design and was registered at EU Clinical Trials Register and Spanish Clinical Studies Registry, EudraCT Number: 2014-003671-30 . Registered 2 September 2014.

Delayed progression of diabetic cataractogenesis and retinopathy by Litchi chinensis in STZ-induced diabetic rats.

CONTEXT: The study was carried out to evaluate the effect of the aqueous fruit pericarp extract of Litchi chinensis (APLC) on parameters which leads to diabetic cataractogenesis and retinopathy in the streptozotocin-induced diabetic rats. OBJECTIVE: The objective of the study is to evaluate the APLC for in vivo antioxidant activity and its role in inhibiting the polyol pathway and formation of advanced glycation end products (AGEs). MATERIALS AND METHODS: The diabetic animals were treated with L. chinensis for a period of 12 weeks. At the end of 12 weeks, the animals were killed and the biochemical pathways involved in the pathogenesis of cataract such as oxidative stress by protein content, superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and polyolpathway by aldose reductase (AR) in lens homogenates, alterations in protein carbonyl content (PCO) and AGEs in both serum and lens the APLC-treated diabetic rats were compared against diabetic control rats. Cataract progression due to hyperglycemia was monitored by slit lamp bio microscope and classified into four stages. Fundoscope test and retinal histopathology were done for assessing retinopathy. RESULTS: Statistically significant reduction in glucose, and elevation of protein content, SOD, CAT, and GSH levels and decreased levels of AR and PCO in lens homogenate and significant reduction in AGEs serum and lens homogenate were observed. Slit lamp examination, fundoscope, and histopathology showed improvement in retinal changes in APLC-treated rats compared to diabetic control animals. CONCLUSION: The treatment with APLC found to delay the progression of diabetic cataractogenesis and retinopathy, which might be due to its antioxidant activity, because of the presence of active phytochemicals in APLC.

Serum Autoantibody Profiling of Patients with Paraneoplastic and Non-Paraneoplastic Autoimmune Retinopathy.

PURPOSE: Although multiple serum antiretinal autoantibodies (ARAs) have been reported in patients with paraneoplastic and non-paraneoplastic autoimmune retinopathy ((n)pAIR), not all retinal antigens involved in (n)pAIR are specified. This study aims to serologically identify patients with presumed (n)pAIR through determination of both known and unknown ARAs by autoantibody profiling. METHODS: An antigen suspension bead array using 188 different antigens representing 97 ocular proteins was performed to detect ARAs in serum samples of patients with presumed (n)pAIR (n = 24), uveitis (n = 151) and cataract (n = 21). Logistic regressions were used to estimate the associations between ocular antigens and diagnosis. Validation of interphotoreceptor matrix proteoglycan 2 (IMPG2) and recoverin antigens was performed by immunohistochemistry and immunoblot, respectively. RESULTS: Samples of patients with presumed (n)pAIR exhibited a broad spectrum of ARAs. We identified retinal antigens that have already been described previously (e.g. recoverin), but also identified novel ARA targets. Most ARAs were not specific for (n)pAIR since their presence was also observed in patients with cataract or uveitis. High titers of autoantibodies directed against photoreceptor-specific nuclear receptor and retinol-binding protein 3 were more common in patients with presumed (n)pAIR compared to uveitis (p = 0.015 and p = 0.018, respectively). The presence of all other ARAs did not significantly differ between groups. In patients with presumed (n)pAIR, anti-recoverin autoantibodies were the most prevalent ARAs. Validation of bead array results by immunohistochemistry (anti-IMPG2) and immunoblot (anti-recoverin) showed concordant results in (n)pAIR patients. CONCLUSIONS: Patients with (n)pAIR are characterized by the presence of a broad spectrum of ARAs. The diagnosis of (n)pAIR cannot be based on the mere presence of serum ARAs, as these are also commonly present in uveitis as well as in age-related cataract patients.

Cystatin C, chronic kidney disease and retinopathy in adults without diabetes.

BACKGROUND: Serum cystatin C, a novel marker of renal function has been shown to be superior to serum creatinine in predicting renal function decline and adverse outcomes of chronic kidney disease (CKD). Our aim was to investigate the association between cystatin C and retinopathy in adults without diabetes. METHODS: We examined 1725 Indian adults, aged 40-80 years who participated in the Singapore Indian Eye Study (2007-2009) and were free of diabetes mellitus. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) determined from serum cystatin C (CKD-eGFRcys, n = 199), and serum creatinine (CKD-eGFRcr, n = 81). Retinopathy was assessed from digital fundus photographs of both eyes by trained graders using the modified Airlie House classification. The associations of CKD defined by the two markers alone and in combination (confirmed CKD, eGFRcr <60 and eGFRcys <60, n = 58) with retinopathy were examined using logistic regression models adjusted for potential confounding factors including preexisting cardiovascular disease and albuminuria. RESULTS: The prevalence of retinopathy among those with CKD-eGFRcr and CKD-eGFRcys was 9.9% and 8.5%, respectively. In separate models, the associations of retinopathy with both CKD-eGFRcys (odds ratio (OR) (95% confidence interval (CI)) = 2.18 (1.14-4.16)) and CKD-eGFRcr were significant (OR (95% CI) = 2.63 (1.10-6.28)). In models including both markers, compared to optimal kidney function (eGFRcr ≥60 and eGFRcys ≥60), confirmed CKD was associated with a fourfold higher odds of retinopathy (OR (95% CI) = 4.01 (1.52-10.60)). CONCLUSIONS: In a population-based sample of Indian adults without diabetes, CKD defined by both cystatin C and creatinine was strongly associated with retinopathy.

Ketocarotenoid circulation, but not retinal carotenoid accumulation, is linked to eye disease status in a wild songbird.

Pathogenic or parasitic infections pose numerous physiological challenges to organisms. Carotenoid pigments have often been used as biomarkers of disease state and impact because they integrate multiple aspects of an individual's condition and nutritional and health state. Some diseases are known to influence carotenoid uptake from food (e.g. coccidiosis) and carotenoid use (e.g. as antioxidants/immunostimulants in the body, or for sexually attractive coloration), but there is relatively little information in animals about how different types of carotenoids from different tissue sources may be affected by disease. Here we tracked carotenoid accumulation in two body pools (retina and plasma) as a function of disease state in free-ranging house finches (Haemorhous mexicanus). House finches in eastern North America can contract mycoplasmal conjunctivitis (Mycoplasma gallisepticum, or MG), which can progress from eye swelling to eye closure and death. Previous work showed that systemic immune challenges in house finches lower carotenoid levels in retina, where they act as photoprotectors and visual filters. We assessed carotenoid levels during the molt period, a time of year when finches uniquely metabolize ketocarotenoids (e.g. 3-hydroxy-echinenone) for acquisition of sexually selected red plumage coloration, and found that males infected with MG circulated significantly lower levels of 3-hydroxy-echinenone, but no other plasma carotenoid types, than birds exhibiting no MG symptoms. This result uncovers a key biochemical mechanism for the documented detrimental effect of MG on plumage redness in H. mexicanus. In contrast, we failed to find a relationship between MG infection status and retinal carotenoid concentrations. Thus, we reveal differential effects of an infectious eye disease on carotenoid types and tissue pools in a wild songbird. At least compared to retinal sources (which appear somewhat more temporally stable than other body carotenoid pools, even to diseases of the eye evidently), our results point to either a high physiological cost of ketocarotenoid synthesis (as is argued in models of sexually selected carotenoid coloration) or high benefit of using this ketocarotenoid to combat infection.

Frequency and risk factors of non-retinopathy ocular conditions in people with diabetes: the Singapore Malay Eye Study.

AIM: To investigate the frequency and risk factors of non-retinopathy ocular conditions in persons with diabetes. METHODS: A population-based cross-sectional study of 3176 Malay persons aged between 40 and 79 years in Singapore was conducted. Cataract, glaucoma, refractive errors, age-related macular degeneration, dry eye, epiretinal membrane, ocular hypertension and retinal conditions were assessed based on standardized interviews, clinical examinations and laboratory investigations. RESULTS: A total of 768 participants (24.2%) had diabetes. People with diabetes were more likely to have cortical cataract (52.1 vs. 37.3%, P < 0.001), ocular hypertension (10.9 vs. 7.4%, P = 0.002) and epiretinal membrane (17.2 vs. 10.1%, P < 0.001) compared with those without diabetes. The odds of having cortical cataract (odds ratio 1.63, 95% CI 1.20-2.20) and epiretinal membrane (among those with previous cataract surgery: odds ratio 1.63, 95% CI 1.20-2.20) were significantly higher in people with diabetes compared with those without. The population attributable risks for cortical cataract and epiretinal membrane because of diabetes were 8.7 and 9.0%, respectively. In persons with diabetes, hypertension and high cholesterol were the major risk factors associated with non-retinopathy eye complications such as ocular hypertension (odds ratio 1.18, 95% CI 1.04-1.33) and retinal emboli (odds ratio 1.99, 95% CI 1.05-3.80). CONCLUSION: Our results allow clinicians to better inform patients with diabetes that they are more likely to have cortical cataract and epiretinal membranes (those with previous cataract surgery) in addition to diabetic retinopathy. Two modifiable risk factors-blood pressure and cholesterol associated with ocular hypertension and retinal emboli, respectively-are also risk factors for non-retinopathy ocular conditions in persons with diabetes.

Lipemia retinalis: a combination of genetics and the American diet and lifestyle.

BACKGROUND: Lipemia retinalis is a well-documented but rate ocular finding directly associated with serum triglyceride levels. The clinical presentation varies with the amount of triglycerides in the blood and completely resolves with lowering triglyceride levels, making this condition transient with no visual symptoms; CASE REPORT: A 46-year old white man presented with lipemia retinalis and, hours later, to the Emergency department with acute pancreatitis secondary to hypertriglyceridemia; CONCLUSION: Lipemia retinalis warrants an immediate complete blood count and lipid panel to Determine triglyceride levels with referral to a primary care provider.

Identification of autoantibodies against TRPM1 in patients with paraneoplastic retinopathy associated with ON bipolar cell dysfunction.

BACKGROUND: Paraneoplastic retinopathy (PR), including cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR), is a progressive retinal disease caused by antibodies generated against neoplasms not associated with the eye. While several autoantibodies against retinal antigens have been identified, there has been no known autoantibody reacting specifically against bipolar cell antigens in the sera of patients with PR. We previously reported that the transient receptor potential cation channel, subfamily M, member 1 (TRPM1) is specifically expressed in retinal ON bipolar cells and functions as a component of ON bipolar cell transduction channels. In addition, this and other groups have reported that human TRPM1 mutations are associated with the complete form of congenital stationary night blindness. The purpose of the current study is to investigate whether there are autoantibodies against TRPM1 in the sera of PR patients exhibiting ON bipolar cell dysfunction. METHODOLOGY/PRINCIPAL FINDINGS: We performed Western blot analysis to identify an autoantibody against TRPM1 in the serum of a patient with lung CAR. The electroretinograms of this patient showed a severely reduced ON response with normal OFF response, indicating that the defect is in the signal transmission between photoreceptors and ON bipolar cells. We also investigated the sera of 26 patients with MAR for autoantibodies against TRPM1 because MAR patients are known to exhibit retinal ON bipolar cell dysfunction. Two of the patients were found to have autoantibodies against TRPM1 in their sera. CONCLUSION/SIGNIFICANCE: Our study reveals TRPM1 to be one of the autoantigens targeted by autoantibodies in at least some patients with CAR or MAR associated with retinal ON bipolar cell dysfunction.

Minimized cardiopulmonary bypass reduces retinal microembolization: a randomized clinical study using fluorescein angiography.

BACKGROUND: The use of minimized cardiopulmonary bypass (MCPB) circuits has recently increased in an attempt to reduce the adverse effects of CPB. This prospective randomized study aimed to determine the effects of MCPB on retinal microembolization and related inflammatory, coagulation, and endothelial markers compared with conventional extracorporeal circulation (CCPB) among patients undergoing coronary artery bypass graft surgery. METHODS: Forty patients entered, and 37 patients completed the study. After the induction of anesthesia and immediately after the termination of CPB, standardized retinal fluorescein angiographs and digital images were obtained on both eyes and analyzed in a blinded fashion in terms of the CPB circuit. Blood samples for inflammatory, coagulation, and endothelial markers were collected at eight time points until the third postoperative day. RESULTS: Postperfusion retinal fluorescein angiographs revealed microembolic perfusion defects in 2 of 18 in the MCPB group and in 9 of 18 in the CCPB group (p=0.027 [11% vs. 50%, difference 39%, confidence interval: 0.087 to 0.613, p=0.029]). Activation of polymorphonuclear leukocytes as measured with polymorphonuclear elastase was significantly decreased in the MCPB group. Other markers of inflammation, coagulation, and endothelial dysfunction increased comparably in both groups during CPB. CONCLUSIONS: Retinal microembolization was found to be decreased after the use of minimized CPB compared with CCPB, suggesting a decreased embolic load to the brain after MCPB.