Harumi Fukushima

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.

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.

Injection of triamcinolone acetonide into the posterior sub-tenon capsule for treatment of diabetic macular edema.

Purpose: To compare eyes that received treatment with untreated fellow eyes to assess the effectiveness of injection of 20 mg of triamcinolone acetonide (TA) into the posterior sub-Tenon capsule for treatment of diabetic macular edema (DME). Methods: Nine adult patients (mean age, 60.4 years) with DME in both eyes were followed up for 3 months after unilateral treatment. We compared central macular thickness before and after treatment with those of the untreated fellow eye. Results: In 9 eyes injected with 20 mg of TA, the mean central macular thickness ± SD was 624.8 ± 173.7 &mgr;m before treatment. In the fellow eyes, it was 452.8 ± 235.2 &mgr;m. There was no significant difference between the two groups (P = 0.10, unpaired t-test). One month after injection, it was 434.0 ± 120.7 &mgr;m in injected eyes (P = 0.017, paired t-test) and 462.2 ± 232.7 &mgr;m in fellow eyes (P = 0.70, paired t-test), and after 3 months, the respective values were 423.1 ± 186.3 &mgr;m (P = 0.052, paired t-test) and 478.3 ± 269.1 &mgr;m (P = 0.65, paired t-test). Conclusion: Injection of 20 mg of TA into the posterior sub-Tenon capsule effectively reduces macular thickening due to DME, at least in the short term.

Structural and functional characterization of gastric mucosa and central nervous system in histamine H2 receptor-null mice.

To examine the physiological role of the histamine H(2) receptor, histamine H(2) receptor-null mice were generated by homologous recombination. Histamine H(2) receptor-null mice, which developed normally and were fertile and healthy into adulthood, exhibited markedly enlarged stomachs and marked hypergastrinemia. The former was due to hyperplasia of gastric gland cells (small-sized parietal cells, enterochromaffin-like cells and mucous neck cells which were rich in mucin), but not of gastric surface mucous cells, which were not increased in number as compared with those in wild-type mice despite the marked hypergastrinemia. Basal gastric pH was slightly but significantly higher in histamine H(2) receptor-null mice. Although carbachol but not gastrin induced in vivo gastric acid production in histamine H(2) receptor-null mice, gastric pH was elevated by both muscarinic M(3) and gastrin antagonists. Thus, both gastrin and muscarinic receptors appear to be directly involved in maintaining gastric pH in histamine H(2) receptor-null mice. Interestingly, gastric glands from wild-type mice treated with an extremely high dose of subcutaneous lansoprazole (10 mg/kg body weight) for 3 months were very similar to those from histamine H(2) receptor-null mice. Except for hyperplasia of gastric surface mucous cells, the findings for gastric glands from lansoprazole-treated wild-type mice were almost identical to those from gastric glands from histamine H(2) receptor-null mice. Therefore, it is possible that the abnormal gastric glands in histamine H(2) receptor-null mice are secondary to the severe impairment of gastric acid production, induced by the histamine H(2) receptor disruption causing marked hypergastrinemia. Analyses of the central nervous system (CNS) of histamine H(2) receptor-null mice revealed these mice to be different from wild-type mice in terms of spontaneous locomotor activity and higher thresholds for electrically induced convulsions. Taken together, these results suggest that (1) gastrin receptors are functional in parietal cells in histamine H(2) receptor-null mice, (2) abnormal gastric glands in histamine H(2) receptor-null mice may be secondary to severe impairment of gastric acid production and secretion and (3) histamine H(2) receptors are functional in the central nervous system.

Use of telemedicine in periodic screening of diabetic retinopathy.

Telemedicine was used for taking ocular fundus images of diabetic patients, which were subsequently sent by electronic mail to experienced ophthalmologists at a university hospital. The ophthalmologists provided reports on the patients to the internists. The objective of the study was to evaluate the effectiveness of this telemedicine system. A total of 279 diabetic patients were admitted to the Third Department of Internal Medicine of Yokohama City University Hospital, School of Medicine, for blood sugar control or for education on lifestyle between April, 1999, and October, 2000. The subjects did not have eye disease nor diabetic retinopathy when evaluated by an ophthalmologist (at either Yokohama City University Hospital or other facility) within 3 months before enrollment in the study. After dilation of the pupil, fundus images were taken of each eye from four angles using a nonmydriatic fundus camera. The images were transmitted by electronic mail to the Division of Ophthalmology of Tokyo University Branch Hospital along with other patient information. The ophthalmologists there evaluated the images on the screen according to Fukudas classification of diabetic retinopathy. They sent ophthalmologic reports to the internists at the Third Department of Internal Medicine of Yokohama City University Hospital, School of Medicine, and recommended whether the patient should be seen by his/her regular ophthalmologist earlier than the next scheduled visit. Fundus images were obtained at the time of admission, at 1, 3, and 6 months after discharge, and at every 6 months thereafter. Out of the images of 1170 eyes obtained at various time points from the 279 patients, 1076 (92.0%) were successfully evaluated by the ophthalmologists at the University of Tokyo, while 60 (5.1%) could not be evaluated and there was a communication problem for the images of 34 eyes. The ophthalmologists determined that 5 eyes of 3 patients required further evaluation by the patients regular ophthalmologist based on the images transferred by telemedicine. No patient dropped out during the study period.

Relationship between anterior capsule contraction and posterior capsule opacification after cataract surgery in patients with diabetes mellitus

Purpose: To prospectively assess the relationship between contraction of the anterior capsule opening and posterior capsule opacification (PCO) after cataract surgery in patients with diabetes mellitus. Setting: Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Kaiya Eye Clinic, Hamamatsu, and Department of Ophthalmology, Institute of Clinical Medicine, University of Tsukuba, Ibaragi, Japan. Methods: This study comprised 45 patients (45 eyes) with diabetes mellitus who had cataract surgery. In all eyes, the anterior capsule opening area and degree of PCO were determined by diaphanoscopy using an anterior eye segment analysis system (EAS‐100, Nidek, Inc.) 1 day and 1 year postoperatively. Results: There was no correlation between the size of the anterior capsule opening area 1 day after surgery and the degree of PCO 1 year after surgery (Pearson correlation coefficient [r] = 0.041; P = .79). The percentage reduction in the anterior capsule opening area from 1 day to 1 year after surgery did not correlate with the degree of PCO 1 year after surgery (r = −0.08; P = .60). Conclusion: Contraction of the anterior capsule opening and PCO after cataract surgery cannot be explained by a common mechanism.

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.

Effect of subconjunctival steroid injection on intraocular inflammation and blood glucose level after cataract surgery in diabetic patients

Purpose: To prospectively evaluate the usefulness of a subconjunctival steroid injection given at the completion of cataract surgery in patients with diabetes mellitus. Setting: University of Tokyo School of Medicine, Tokyo, Kaiya Eye Clinic, Hamamatsu, and Jyosai Hospital, Tokyo, Japan. Methods: One hundred four eyes of 104 diabetic patients having routine small incision cataract surgery were randomized into 2 groups. One group received a subconjunctival injection of dexamethasone and the other group did not. Aqueous flare intensity was measured with the laser flare meter preoperatively and 1, 2, 5, 7, and 14 days postoperatively. Another 19 diabetic patients having routine cataract surgery were randomized to receive a subconjunctival steroid injection or not; blood glucose concentration was measured 4 times a day for 3 days postoperatively. Results: There was no significant difference between the 2 groups in aqueous flare values at any postoperative time. The subconjunctival steroid injection induced a transient but significant increase in blood glucose on the day of surgery. Conclusion: A subconjunctival steroid injection given at the completion of cataract surgery in diabetic patients had no beneficial effects.

Influence of subconjunctival steroid injection on blood glucose profile in diabetic rats.

Purpose The influence of subconjunctival steroid injection on blood glucose concentration was investigated in rats with streptozotocin (STZ)-induced diabetes.Methods Adult male Wistar rats with STZ-induced diabetes (n = 10) and normal controls (n = 10) received subconjunctival injections of 0.1 ml of 0.4% dexamethasone or saline. Blood glucose concentrations were measured before and 3, 6, 12, 18 and 24 h after treatment.Results In the STZ group, subconjunctival injection of steroids (p = 0.0013) or saline (p = 0.0037) significantly increased the blood glucose level 3 h after treatment. In the control group, the blood glucose concentration was not elevated by subconjunctival injection. In both STZ and control groups, the blood glucose concentration was significantly higher after steroid injection than after saline injection throughout the 24 h study period.Conclusions Subconjunctival steroid injection induced a significant blood glucose increase in both diabetic and control rats. For diabetic rats, the subconjunctival injection itself constituted stress that resulted in glucose elevation.

Screening for diabetic retinopathy using new mydriasis-free, full-field flicker ERG recording device

Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Therefore, it is important to detect DR accurately during mass screening. The purpose of this study was to determine whether a small, hand-held, mydriasis-free, full-field flicker electroretinographic (ERGs) device called RETeval can be used to screen for DR. To accomplish this, we recorded full-field flicker ERGs with this device from 48 normal eyes and 118 eyes with different severities of DR in patients with diabetes mellitus (DM). This system delivered a constant flash retinal luminance by adjusting the flash luminance that compensated for changes in the pupil size. Our results showed that there were significant correlations between the severity of DR and the implicit times (P < 0.001; r = 0.55) and the amplitudes (P = 0.001; r = −0.29). When the implicit time was used for the index, the area under the receiver operating characteristic curve was 0.84 for the detection of DR, and was 0.89 for the detection of DR requiring ophthalmic treatments. These results suggest that the implicit times of the flicker ERGs recorded by the small, mydryasis-free ERG system can be used as an adjunctive tool to screen for DR.