Shigehiko Kitano

Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with diabetic macular edema and other retinal disorders

PURPOSE To investigate the correlation between angiotensin II (AII) or vascular endothelial growth factor (VEGF) levels in the vitreous fluid and the severity of diabetic macular edema (DME). DESIGN A case-control study. METHODS Vitreous fluid samples were obtained at the time of vitreoretinal surgery from 20 eyes of 20 patients with DME, 6 eyes of 6 diabetic patients without retinopathy, and 14 eyes of 14 nondiabetic patients. The VEGF levels in vitreous fluid and plasma were determined by enzyme-linked immunosorbent assay, while AII levels were measured by radioimmunoassay. RESULTS The vitreous concentration of VEGF was significantly higher in patients with DME than in nondiabetic patients or diabetic patients without retinopathy (P <.0001 and P <.0001, respectively). Vitreous levels of AII were also higher in patients with DME than in nondiabetic patients (P =.0082). The vitreous concentration of AII was significantly correlated with that of VEGF (P =.0022). Vitreous concentrations of both AII and VEGF were significantly higher in patients with hyperfluorescent DME than in those with hypofluorescent (P =.0228 and P =.0068, respectively). CONCLUSIONS We found that the levels of both AII and VEGF were elevated in the vitreous fluid of patients with hyperfluorescein DME. Our results suggest that both AII and VEGF are related to the increase of vascular permeability in DME.

Relation between retrobulbar circulation and progression of diabetic retinopathy

Aims: To investigate retrobulbar circulatory parameters in type 2 diabetic patients with and without diabetic retinopathy (DR) progression. Methods: This was a prospective cohort study. One eye of 35 diabetic patients with background DR (BDR) were included in the study. Eyes without DR, with proliferative DR, photocoagulation, past surgical procedures, or other ophthalmic disease except BDR and cataract were excluded. The study was masked. Colour Doppler imaging (CDI) was used to measure the retrobulbar circulation at the beginning of the study and after a mean follow up interval of 21 months. Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistivity index (RI) in the central retinal artery and vein and the posterior ciliary artery were measured. Results: 18 patients who developed DR progression showed significantly increased central retinal vein PSV ( 5.6 (3.5–9.1) p = 0.003), EDV ( 3.4 (2.3–4.4) p = 0.04), and RI ( 0.43 (0.20–0.56) p = 0.02) at the final measurement compared to the initial measurement (PSV = 4.6 (3.2–7.0); EDV = 3.0 (2.3–3.7); RI = 0.40 (0.17–0.52)). Circulatory parameters in the central retinal artery and the posterior ciliary artery did not alter significantly after progression of DR. 17 patients were without DR progression and they did not show any significant differences in the measured circulatory parameters on entry compared to the final measurement. Conclusion: The authors suggest that the initial changes in the retrobulbar circulation during DR progression occur in the central retinal vein.

Efficacy of bromfenac sodium ophthalmic solution in preventing cystoid macular oedema after cataract surgery in patients with diabetes

Acta Ophthalmol. 2010: 88: 896–900

Glycemic control and lens transparency in patients with type 1 diabetes mellitus.

PURPOSE To assess quantitatively the cumulative effect of hyperglycemia on lens transparency in patients with juvenile type 1 diabetes mellitus. METHODS Subjects were 30 patients (30 eyes) with type 1 diabetes mellitus who had well-documented records on the duration of diabetes mellitus and condition of glycemic control from the onset. They were 35 years of age or younger (mean, 26.0 years), had a history of type 1 diabetes mellitus at least 5 years (mean, 8.4 years), had corrected visual acuity of 20/20 or better, and showed no clinically apparent cataract on slit-lamp examination. Twenty-one eyes of 21 subjects served as age-matched normal controls. They were 35 years of age or younger (mean, 25.7 years), had no diabetes mellitus, had corrected visual acuity of 20/20 or better, and showed no signs of cataract on slit-lamp examination. The degree of lens opacity was quantified using the anterior eye segment analysis system based on the Scheimpflug principle. An index was created to represent the cumulative effect of long-term glycemic control (hyperglycemic accumulation) by multiplying the average hemoglobin A(1c) value and the number of months from the onset. RESULTS The patients with diabetes mellitus exhibited significantly greater degree of lens opacity than the normal controls (P =.017, Mann-Whitney U-test). Among the patients with diabetes mellitus, the lens opacity was greater in eyes with retinopathy than those without retinopathy (P =.011). Multiple regression analysis revealed that only the index of hyperglycemic accumulation significantly correlated with the degree of lens opacity (P =.042). CONCLUSION Accumulated effect of hyperglycemia is related to the lens transparency in patients with diabetes.

Influence of rapid glycemic control on lens opacity in patients with diabetes mellitus

PURPOSE To report the influence of rapid glycemic control on lens opacity in patients with diabetes mellitus. METHODS In a prospective study, nine patients with adult onset diabetes mellitus and glycosylated hemoglobin values over 9% were divided into two groups, rapid glycemic control and slow glycemic control groups, based on the time course of glycosylated hemoglobin values after the initiation of glycemic control. The lens thickness and opacity were measured using the anterior eye segment analysis system. RESULTS One week after onset of treatment, the lens in rapid glycemic control group became significantly thicker than in pretreatment, but returned to the baseline level at the subsequent measurement points. The lens opacity index in the rapid glycemic control group increased significantly (P <.01, paired t test) 4 months after the glycemic control, which persisted throughout the 1-year study period. The lens thickness and opacity in the slow glycemic control group did not change significantly. CONCLUSION It was suggested that rapid glycemic control can induce an irreversible increase in lens opacification.

Transport of fluorescein in the rabbit eye after treatment with sodium iodate

The outward active transport and the inward permeability of the blood-retinal barrier were studied in the rabbit eye after i.v. administration of sodium iodate. The active transport was evaluated from the half-time of disappearance of the vitreous fluorescein following intravitreal administration, and the inward permeability was evaluated from the vitreous concentration of fluorescein monoglucuronide after i.v. administration. The half-time of the vitreous fluorescein was 3.5 +/- 0.3 (mean +/- S.D.) hr, and 3.9 +/- 0.2 hr before and within 6 hr after iodate administration, respectively. After 24 hr, the half-time was 11.7 +/- 1.7 hr, similar to that of fluorescein monoglucuronide, 12.0 +/- 2.7 hr. The vitreous and the anterior chamber concentration of fluorescein monoglucuronide was measured at 1 hr after the i.v. dye injection. The vitreous concentration in the rabbits given iodate 3 hr before the dye injection was significantly greater than in the normal eyes, while the anterior chamber concentration was not different. Since fluorescein is rapidly metabolized to fluorescein monoglucuronide, differences in parameters determined using systemic fluorescein under two treatments or in disease states may be the result of alteration of the dynamics of fluorescein, fluorescein monoglucuronide, or both.

Prediction of Retinopathy at 20 Years After Onset in Younger-Onset Type 1 Diabetes Using Mean Metabolic Memory-Free HbA1c Values: The importance of using HbA1c data of total, not partial, diabetes duration

OBJECTIVE Metabolic memory, in which past hyperglycemia could affect future retinopathy, is a potential issue in studying the relationship between glycemia and retinopathy. We examined retrospectively if mean “metabolic memory-free” glycosylated hemoglobin A1C (HbA1c) values covering total diabetes duration could predict retinopathy in younger-onset type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS Inclusion criteria were T1DM onset before age 30 years, first visit to our center between 1988 and 1990 soon after onset, continuous HbA1c data for 20 years, and a 20-year follow-up retinopathy examination. Retinopathy predictive capabilities of HbA1c variables were examined. RESULTS Of 15 subjects, 5 were retinopathy-positive and 10 were retinopathy-negative at the 20-year follow-up. Mean metabolic memory-free HbA1c values for the 20 years showed a substantial capacity to predict retinopathy at 20 years. The longer the period without HbA1c data following onset in simulation, the less accurate the prediction. CONCLUSIONS HbA1c values may predict retinopathy better if metabolic memory-free data are used.

Retinopathy in older patients with diabetes mellitus

PURPOSE We studied the effects of the age and/or disease duration in diabetics on the progression of diabetic retinopathy (DR). METHODS The population consisted of 3614 type 2 diabetes mellitus (DM) patients. The subjects were divided into three age groups (elderly, > or = 65 years old; middle-aged, 64-40 years old, and younger < 40 years old) for disease duration-adjusted comparison with and without DR and proliferative diabetic retinopathy (PDR). Then, in 503 patients with 8-year follow-up data available, the frequency of development/progression of DR and the rate of progression to PDR were compared among the three groups. Thirdly, in the elderly patients, DR prevalence and the frequency of the development/progression of DR were compared between two groups with different diabetes duration (> or = 6 years and < or = 5 years). RESULTS The prevalence of DR increased significantly with age (P < 0.001). The prevalence of PDR decreased significantly with age (P < 0.001). The overall frequency of the development and/or progression of DR increased significantly with age (P = 0.002); however, age was not related to the frequency of progression to PDR. In the patients with diabetes duration of 6-15 years, the frequency of the development/progression of DR and of progression to PDR after an 8-year follow up tended to decrease with age. Elderly patients with a diabetes duration of > or = 6 years showed significantly higher rate of prevalence of DR and frequency of development/progression of DR in an 8-year period than those with diabetes of a shorter duration (P < 0.001 and P < 0.001, respectively). CONCLUSION In elderly DM patients, the prevalence of DR was increased even in the short duration and development/progression rates of DR were increased, while the relative frequency of PDR was decreased. Older-onset DM patients appear to be at a lower risk for progression to PDR.

HLA typing is not predictive of proliferative diabetic retinopathy in patients with younger onset type 2 diabetes mellitus

Chronic hyperglycaemia and the duration of diabetes are the most important factors in retinopathy. However, retinopathy progresses in some patients despite good glycaemia control. Also, poor glycaemia control does not always lead to retinopathy in younger onset patients, while still others develop severe retinopathy that is resistant to retinal photocoagulation. These facts suggest that the risk factors for diabetes and retinopathy are not necessarily the same, and that the development of severe retinopathy may be influenced by genetic factors.1 Human leucocyte antigen (HLA) status has a significant role in immune responses and immunological tolerance and is a factor in the onset of type 2 diabetes.2–4 DR4, DR8, DR9, and several antigens of the DQ region are related to retinopathy in patients with type 1 diabetes.5,6 In addition, it was reported that HLA-DR was expressed in proliferative retinopathy.7,8 Little is known, however, about the relation between retinopathy with type 2 diabetes and the HLA antigen. Furthermore, most previous studies have not taken into consideration the background of glycaemic control or the duration of the diabetes. A group of younger onset type 2 diabetes patients with PDR, and a group who had no …

Association of systemic health and functional outcomes with changes in hard exudates associated with clinically significant macular oedema over the natural course of the disease

Aim Hard exudates associated with clinically significant macular oedema (CSMO) do not always increase without laser photocoagulation and can generally be classified as regressing or progressing. We studied the systemic differences and functional outcomes between the two groups. Methods In this retrospective observational controlled study, we compared blood pressure, biochemical parameters and best corrected visual acuity (BCVA) between 26 patients with regressed hard exudates with CSMO (group A) and 27 patients with progressing hard exudates with CSMO (group B). The eyes had no history of ophthalmic treatments including laser therapy for diabetic retinopathy or maculopathy until the end of the study. Results Group B had significant increases in the mean total cholesterol (TC) (p=0.0194) and mean low-density lipoprotein (LDL) cholesterol (p=0.0147) after at least 6 months of follow-up compared with group A. The final mean BCVA was significantly (p=0.0189) higher in group A than group B. A separate within-group analysis showed a significant (p=0.0015) decrease in BCVA from baseline in group B at the final visit. Conclusion For hard exudates associated with CSMO, strict lipid-lowering therapy, especially regulation of elevated TC and LDL, before a decrease in visual acuity might result in better macular anatomical outcomes and visual preservation through the natural course of the disease.