A comparison in the ability to detect diabetic retinopathy between fasting plasma glucose and HbA1c levels in a longitudinal study.

Aims: The relationship between HbA1c and diabetic retinopathy is expected to differ between different races. In this study, we verified which of HbA1c and fasting plasma glucose (FPG) is more effective for detecting the diabetic retinopathy longitudinally in a Japanese population. Materials and Methods: The study subjects underwent health examinations twice (including eye test and questionnaire of lifestyle and health) in 2008-2009 (baseline) and in 2012-2013 (4-year follow-up). Both non-DM and DM patients at baseline were included as the participants. Of these participants, who had not been diagnosed with retinopathy at the baseline survey (n = 2427; 2150 men and 277 women) had eye fundus photographs taken four years later (follow-up survey). The odds ratios of incidence of retinopathy according to the eight groups of FPG and HbA1c were estimated using multiple logistic regression analysis adjusted for sex and age. Receiver operator characteristic analysis was used to evaluate each value associated with the presence or absence of retinopathy. Results: The odds ratios (95% confidence intervals) of incidence of retinopathy by HbA1c level categories, in ascending order, were 1.0 (ref.), 5.66 (1.14-28.26), 1.69 (0.24-12.04), 3.03 (0.50-18.28), 1.04 (0.09-11.59), 4.73 (0.78-28.69), 4.12 (0.74-22.85) and 24.47 (5.61-106.75). For both FPG and HbA1c levels, the odds ratio for the development of retinopathy increased linearly with the increases in the levels FPG and HbA1c, and no clear threshold was observed. The AUC values (SE) for FPG and HbA1c were almost the same, at 0.750 (0.046) and 0.732 (0.048). Conclusions: It was clarified that the higher the level of FPG and HbA1c was, the higher the incidence of retinopathy after 4 years was. There was no clear threshold. The detection ability of the incidence of retinopathy was almost the same between FPG and HbA1c, suggesting it is possible to detect the risk of retinopathy by HbA1c only.

A Comparison of the Association of Fasting Plasma Glucose and HbA1c Levels with Diabetic Retinopathy in Japanese Men.

INTRODUCTION: The relationship between HbA1c and diabetic retinopathy is expected to differ between different races. This study was designed to verify whether HbA1c or fasting plasma glucose (FPG) is more effective in detecting diabetic retinopathy in a Japanese population. MATERIALS AND METHODS: The study subjects underwent health examinations between 2008 and 2009 with fasting. Of these participants, we analyzed the data for 2,921 Japanese men who had undergone an ophthalmologic examination. Retinopathy was classified into 7 categories according to a simplified diabetic retinopathy scale. The odds ratios of retinopathy according to the eight groups of FPG and HbA1c were estimated using multiple logistic regression analysis adjusted for age. Receiver operator characteristic analysis was used to evaluate each value associated with the presence or absence of retinopathy. Results and Discussion. The odds ratios (95% CI) of retinopathy for HbA1c level categories, in ascending order, were 1.0 (ref.), 0.88 (0.28-2.75), 1.27 (0.44-3.69), 1.52 (0.48-4.79), 1.89 (0.52-6.85), 2.70 (0.66-11.10), 4.10 (0.80-21.00), and 6.34 (2.37-16.97) where the odds ratios significantly increased with HbA1c ≥ 6.8%. The area under the curve (SE) for FPG and HbA1c was almost the same, at 0.668 (0.043) and 0.680 (0.043), respectively. CONCLUSIONS: It was clarified that the higher the level of HbA1c, the higher the prevalence of retinopathy, and there was no clear threshold. The detection ability of retinopathy was almost the same, suggesting that it is possible to detect the risk of retinopathy by HbA1c only.

Angiopoietin-like protein 4 (ANGPTL4) is induced by high glucose in retinal pigment epithelial cells and exhibits potent angiogenic activity on retinal endothelial cells.

PURPOSE: Hyperglycaemia has been identified as major risk factor for diabetic retinopathy (DR). It is widely accepted that the progression of DR is mainly due to a local imbalance of pro- versus anti-angiogenic factors in the retina. In this study, we investigated whether retinal pigment epithelial (RPE) cells produced pro-angiogenic factors under high glucose (HG) conditions in vitro. METHODS: Cultured human retinal endothelial (RE) cells were exposed to conditioned medium from retinal pigment epithelium cells (ARPE-19) grown in HG medium and assessed for tube formation. Based on the expression profiles of ARPE-19, we investigated whether ANGPTL4 was a major angiogenic factor released from ARPE-19 under HG conditions using cultured human RE cells as the test system for experiments with recombinant protein, conditioned medium from ARPE-19 and RNA interference (RNAi). RESULTS: The conditioned medium from ARPE-19 cultured under HG conditions promoted tube formation of cultured human RE cells. GeneChip analysis showed that ANGPTL4 was one of the highest upregulated genes under HG conditions. In addition, recombinant ANGPTL4 promoted all of the elements of angiogenesis in human RE cells in vitro. The results of experiments using conditioned medium from ARPE-19 combined with RNAi demonstrated that ANGPTL4 was a major angiogenic factor released from ARPE-19 under HG conditions. CONCLUSIONS: ANGPTL4 was induced by high glucose in RPE cells and exhibited potent angiogenic activity on RE cells. Our results are unique and may potentially add a new candidate to the long list of molecules involved in diabetic retinopathy.

A case of vasoproliferative retinal tumor complicated by neovascular glaucoma.

PURPOSE: To report a case of vasoproliferative retinal tumor complicated by neovascular glaucoma that showed remission after vitrectomy surgery to remove the tumor. METHODS: A 78-year-old man was referred to the hospital with a complaint of visual loss in his right eye. Corrected visual acuity was 0.5 in the right eye and 1.2 in the left eye. The right eye showed mild vitreous hemorrhage and an elevated lesion in the lower fundus. Fluorescein angiography demonstrated leakage from the tumor, and a 4-mm lesion of high density was seen on computed tomography, and we diagnosed it as retinal capillary hemangioma. In this case, von Hippel-Lindau disease was negative. During the course of the disease, peripheral anterior synechia and neovascularization was seen in the iris and angle, and vitreous surgery was enforced to remove the tumor because of increased intraocular pressure. The tumor was removed as almost one mass. Histologically, the tumor was composed of glial cells and small vessels proliferation. We diagnosed vasoproliferative retinal tumor. RESULTS: Seven months after surgery, the intraocular pressure stabilized, and neovascularization of the iris and angle disappeared. Visual acuity was 0.03 due to epiretinal membrane and optic atrophy. There were no signs of recurrence. CONCLUSION: The vitreous surgery is one of the effective treatment methods against vasoproliferative retinal tumor complicated by neovascular glaucoma.

[Macular ischemia following intravitreal bevacizumab therapy for diabetic macular edema].

PURPOSE: To examine the effects of macular ischemia after intravitreal bevacizumab (IVB) in patients with diabetic macular edema(DME). METHODS: Thirty-three eyes of 33 patients with DME were treated with IVB. Fluorescein angiography (FA) was conducted before and 3 months after IVB, the pretreatment sizes of the foveal avascular zone (FAZ) calculated by FA were compared to the values at 3 months after IVB. This study was approved by the Chiba University Hospital Clinical Research Ethics Committee. RESULTS: After IVB, the size of the FAZ enlarged significantly (p = 0.03). Among the 33 patients treated with IVB, 2 patients (6%) had advanced macular ischemia with an FAZ enlarged by 50% or more. In both patients, the visual acuity did not worsen and the foveal thickness decreased. CONCLUSIONS: It is possible that IVB led to macular ischemia.

[Severe case of cytomegalovirus-associated immune reconstitution syndrome in AIDS].

BACKGROUND: Immune reconstitution syndrome (IRS) is a complication caused by reactivation of the immune system that can occur after starting highly active antiretroviral therapy (HAART) in patients with acquired immunodeficiency syndrome (AIDS). Severe IRS associated with cytomegalovirus (CMV) in both eyes who had lost his left vision is reported. CASE: A 37-year-old man with AIDS who had started HAART discontinued his medication. Two weeks after the re-induction of HAART, he suffered CMV retinitis OU. Vitreous opacity OU appeared 3 days later, and optic neuritis OS appeared 6 days after the onset; and visual acuity OS decreased to 0.06. As the number of CD 4 positive T lymphocytes (CD 4) increased from 39 to 118/microl in both the pre- and- post HAART, we diagnosed IRS and started anti- CMV and systemic steroid therapy and discontinued the HAART. The focus of CMV retinitis was improved; however, visual acuity OS did not improve. CONCLUSION: Severe IRS with visual loss induced by CMV retinitis after HAART needs to be considered in low CD 4 level patients during the induction phase.

[Ocular complications in patients with human immunodeficiency virus infection].

PURPOSE: To evaluate the recent clinical manifestations of ocular complications in patients with human immunodeficiency virus(HIV) infection. METHODS: We retrospectively reviewed the medical records of 94 new HIV-positive patients examined at the International Medical Center of Japan between April 1, 2002, and March 31, 2003, and listed the details of ocular complications. The use of highly active antiretroviral therapy (HAART) and CD 4 cell counts was also recorded in patients with cytomegalovirus (CMV) retinitis and iritis/vitritis. RESULTS: The following ocular complications were recognized in 31 patients: retinal microvasculopathy (11 cases), CMV retinitis (10 cases), inactive inflammatory changes (6 cases), iritis/vitritis (5 cases), optic nerve atrophy (2 cases), papilledema (2 cases), ocular tuberculosis (1 case), progressive outer retinal necrosis (1 case) and conjunctival Kaposi's sarcoma (1 case). In patients with CMV retinitis, the CD 4 cell counts at the onset were lower than 50/microl except in 1 case. Iritis and/or vitritis were recognized in 5 cases, and the onset of 4 cases occurred after the beginning of HAART. Among the patients studied, immune recovery uveitis was suspected in 3 patients with a history of CMV retinitis. CONCLUSIONS: Ocular complications were recognized in almost one third of the patients in our series. Immune recovery uveitis was suspected in 3 patients with iritis/vitritis who previously had CMV retinitis.

Acute Korsakoff syndrome following mammillothalamic tract infarction.

There are limited case reports of structural lesions causing Korsakoff syndrome. This report describes acute Korsakoff syndrome following localized, bilateral infarction of the mammillothalamic tracts (MTTs). Axial T2-weighted imaging revealed the lesions at the lateral wall level of the third ventricle and diffusion-weighted imaging confirmed that the left lesion was new and the right old. Korsakoff syndrome persisted 6 months after the onset. This case suggests that bilateral MTT dysfunction can lead to Korsakoff syndrome.

The skin-lightening effects of artocarpin on UVB-induced pigmentation.

This study was conducted to evaluate the effects of the prenylated flavonol artocarpin from the heartwood of Artocarpus incisus on ultraviolet (UV)-induced hyperpigmentation of guinea pig skin. An efficient lightening effect was observed following topical application of artocarpin to UV-stimulated hyperpigmented dorsal skins of brownish guinea pigs.