Tomoaki Shiba

Nocturnal Intermittent Serious Hypoxia and Reoxygenation in Proliferative Diabetic Retinopathy Cases

PURPOSE To clarify the relationship between evaluation items of sleep-disordered breathing and diabetic retinopathy in detail. DESIGN Cross-sectional comparative study. METHODS Sixty-eight consecutive nonproliferative diabetic retinopathy and 151 proliferative diabetic retinopathy (PDR) cases who had undergone surgeries in our department were included in this study. Pulse oximetry was conducted overnight and mean oxygen saturation by pulse oximeter (SpO(2); %), the sleeping 4% oxygen desaturation index (4% ODI times/hour), lowest SpO(2) (%), and the cumulative percent time spent at SpO(2) < 90% (CT 90%) were calculated. The results were evaluated and compared between the 2 groups. In addition, these results and preoperative patient background factors were analyzed using logistic regression analysis to clarify risk factor of PDR. RESULTS 4% ODI and CT 90% in the PDR group were significantly higher than in the nonproliferative diabetic retinopathy group (4% ODI, 7.8 vs. 4.9; P = .007; CT 90%, 2.2 vs 0.8; P = .0006). Lowest SpO(2) was significantly lower in the PDR group than in the nonproliferative diabetic retinopathy groups (82.4 vs 87.0; P = .0006). Logistic regression analysis identified being younger, having a lower value for the lowest SpO(2), and a high hemoglobin A1c value to be risk factors for PDR (age: odds ratio, 0.90; 95% confidence interval, -0.86 to -0.94; P < .0001; lowest SpO(2): odds ratio, 0.93; 95% confidence interval, 0.88 to 0.99; P = .02; hemoglobin A1c: odds ratio, 1.00 to 1.69; P = .047). CONCLUSIONS This study indicated that PDR cases had episodes of nocturnal intermittent hypoxia and reoxygenation as a result of sleep-disordered breathing and that low-value lowest SpO(2) were the risk factors for PDR development.

Relationship between diabetic retinopathy and sleep-disordered breathing.

PURPOSE To clarify the relationships of sleep-disordered breathing (SDB) to nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). DESIGN Cross sectional case-control study. METHODS Forty-eight consecutive NPDR and 118 PDR cases that had undergone surgery in our hospital were included in this study. Pulse oximetry was conducted during the night and the sleeping 4% oxygen desaturation index (ODI) (number of oxygen desaturation events/hour exceeding 4%) and mean SpO(2)% were calculated. If 4% ODI > 5 times/hour, SDB was diagnosed. The results were evaluated and compared between the 2 groups. In addition, these results and preoperative patient background factors were analyzed using multiple regression analysis to identify correlations with the diagnosis of PDR. RESULTS Twenty-nine percent of the NPDR and 48% of the PDR patients were diagnosed as having SDB. The incidence of SDB and the 4% ODI/hour value were significantly higher in the PDR than in the NPDR group (P = .003 and .03, respectively). Multiple regression analysis showed younger age and a higher 4% ODI value to be factors independently contributing to a diagnosis of PDR (age, standard regression coefficient = -0.34; t value = -4.44; P < .0001; 4% ODI, standard regression coefficient = 0.20; t value = 2.15; P = .03, correlation coefficient (R) = 0.43). CONCLUSION Our results suggest that, in diabetic retinopathy patients with nocturnal desaturation, reoxygenation caused by SDB may relate to the development of PDR.

Changes in the blood flow of the optic nerve head induced by different concentrations of epinephrine in intravitreal infusion during vitreous surgery.

PURPOSE We investigated whether intravitreal infusion solution containing epinephrine affects optic nerve head (ONH) blood flow during vitreous surgeries. METHODS The subjects were 22 patients with epimacular membrane or idiopathic macular hole. During vitreous surgery, ONH blood flow was examined before and 10 minutes after intravitreal infusion of solution containing epinephrine, via a laser speckle flowgraphy (LSFG) technique modified for acquiring measurements in a supine position. Epinephrine concentration was set at 1.0 mg/500 mL (1:500,000) or 0.5 mg/500 mL (1:1,000,000), with each concentration assigned to 11 consecutive patients. Relative pupil diameter, IOP, blood pressure, and pulse rate also were measured. RESULTS A significant reduction in blood flow throughout the ONH was induced by intravitreal infusion of epinephrine at 1:500,000, but not at 1:1,000,000. Blood flow in ONH tissue was diminished at both concentrations, while that in vessels of the ONH was not altered significantly by either concentration. Both epinephrine concentrations induced significant pupillary dilatation, but no significant changes in IOP, blood pressure, or pulse rate. CONCLUSIONS This study suggests that epinephrine, used in combination with intravitreal infusion solution, may decrease ONH blood flow during vitreous surgeries, as indicated by measurements obtained via a modified LSFG technique. Attention must be paid to the effects of intravitreal infusion of epinephrine on ocular circulation, particularly ONH blood flow.

Relationship between Severity of Obstructive Sleep Apnea Syndrome and Retinal Nerve Fiber Layer Thickness

PURPOSE To determine whether there is a significant correlation among the peripapillary retinal nerve fiber layer (RNFL) thickness, foveal thickness, total macular volume, and severity of obstructive sleep apnea syndrome. DESIGN Prospective study. METHODS We studied 124 consecutive subjects who underwent polysomnography. Optical coherence tomography (OCT) was used to measure the peripapillary RNFL, foveal thickness, and total macular volume. The Pearson correlation coefficient was used to determine the relationship between the apnea-hypopnea index and OCT and other parameters. Multiple regression analysis was used to determine the independent factors for the RNFL sectors that were the most strongly correlated with the apnea-hypopnea index. RESULTS The apnea-hypopnea index was significantly and negatively correlated (right eye, r = -0.31, P = 0.0004; left eye, r = -0.39, P < 0.0001) with the nasal RNFL thickness (Pearson correlation analysis). The foveal thickness and total macular volume were not correlated. The intraocular pressure, body mass index, plaque score, and incidence of hypertension were negatively correlated, and the lowest oxygen saturation and mean oxygen saturation were positively correlated with the nasal RNFL thickness in the left eye. Multiple regression analysis showed that the apnea-hypopnea index and age were independent contributors to the nasal RNFL thickness in the left eye (apnea-hypopnea index, standard regression coefficient, -0.30, t value, -2.76, P = 0.007; age, -0.24, -2.36, 0.02, respectively). The nasal RNFL thickness in both eyes decreased significantly based on the severity of the obstructive sleep apnea syndrome. CONCLUSION Exacerbation of obstructive sleep apnea syndrome may produce unique retinal neurodegenerative disorders that decrease the nasal RNFL thickness.

Enhanced Circulating Soluble LR11 in Patients With Diabetic Retinopathy

PURPOSE To investigate the relationship of circulating levels of soluble form of LR11 (sLR11; also called SorLA or SORL1), with the progression of proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus. DESIGN Cross-sectional study. METHODS Fifty-four patients with type 2 diabetes mellitus were divided into 2 sex- and age-matched groups: one with PDR (n = 29) and the other with nonproliferative diabetic retinopathy (n = 25). The serum sLR11 levels were measured with an immunodetection system followed by chemifluorescence quantification. RESULTS The serum sLR11 levels were higher in the PDR group than in the nonproliferative diabetic retinopathy group (5.8 ± 1.2 U vs 3.7 ± 1.3 U; P < .01). A multivariate regression analysis showed that circulating sLR11 is a factor contributing to the prediction of PDR independent of other classical risk factors, and an area under the receiver operating characteristic curve analysis revealed that the sensitivity and the specificity were equivalent to or more than those of other factors. Among the classical risk factors for PDR, glycosylated hemoglobin levels showed the highest correlation coefficient (P < .01) for the sLR11 concentrations. CONCLUSIONS Serum sLR11 concentration may reflect the progression of PDR in patients with type 2 diabetes mellitus. sLR11, released from immature vascular cells and indicating the development of atherosclerosis, is expected to be a novel candidate biomarker indicating diabetic retinopathy in patients with type 2 diabetes mellitus.

Pulse-Wave Analysis of Optic Nerve Head Circulation Is Significantly Correlated with Kidney Function in Patients with and without Chronic Kidney Disease

Aim. To determine whether there is a significant correlation between the optic nerve head (ONH) circulation determined by laser speckle flowgraphy (LSFG) and kidney function. Materials. Seventy-one subjects were investigated. The estimated glomerular filtration rate (GFR) and serum creatinine, cystatin C, and urinary albumin excretion were measured. The ONH circulation was determined by an analysis of the pulse wave of LSFG, and this parameter was named blowout time (BOT). Chronic kidney disease (CKD) was defined to be present when the estimated GFR was <60 mL/min per 1.73 m2. Pearsons correlation coefficients were used to determine the relationship between the BOT and the kidney function. We also examined whether there were significant differences in all parameters in patients with and without CKD. Results. BOT was significantly correlated with the level of creatinine (r = −0.24, P = 0.04), the estimated GFR (r = 0.42, P = 0.0003), cystatin C (r = −0.29, P = 0.01), and urinary albumin excretion (r = −0.29, P = 0.01). The BOT level in subjects with CKD was significantly lower than that in subjects without CKD (P = 0.002). Conclusion. BOT in ONH by LSFG can detect the organ damage such as kidney dysfunction, CKD.

Relationship Between Sleep-Disordered Breathing and Iris and/or Angle Neovascularization in Proliferative Diabetic Retinopathy Cases

PURPOSE To investigate whether sleep-disordered breathing is a risk factor for iris and/or angle neovascularization in patients with proliferative diabetic retinopathy (PDR). DESIGN Cross-sectional comparative case series. SUBJECTS AND METHODS One hundred fifty-one consecutive patients with PDR who underwent surgery in our hospital were divided based on the presence of iris and/or angle neovascularization (NV group, 37 patients) or absence of NV (non-NV group, 114 patients). Pulse oximetry was conducted during the night and the mean SpO(2), 4% oxygen desaturation index (4% ODI times/hour), the lowest SpO(2)% during sleep (lowest SpO(2)), and the cumulative percentage of time at SpO(2) <90% in analysis times (CT90%) were calculated. When the 4% ODI exceeded 5 times/hour, sleep-disordered breathing was diagnosed. The results were compared between the 2 groups. Preoperative systemic parameters also were analyzed by logistic regression to clarify risk factors for the NV group. RESULTS A mean total of 50% (62% of the NV group and 46% of the non-NV group) was diagnosed with sleep-disordered breathing. The mean SpO(2) and lowest SpO(2) did not differ significantly between the 2 groups; the 4% ODI (12.3 vs 6.6) and CT90% (3.8 vs 1.7) were significantly higher in the NV group (P=.02, for both comparisons). Logistic regression analysis identified insulin therapy (odds ratio [OR], 3.01; 95% confidence interval [CI], 1.26∼7.20; P=.01); and 4% ODI (OR, 1.09; CI, 1.01∼1.16; P=.02) as risk factors for the NV group. CONCLUSIONS In patients with PDR, nocturnal intermittent hypoxia/reoxygenation resulting from sleep-disordered breathing may be a risk factor for iris and/or angle neovascularization.

Relevance of the serum apolipoprotein ratio to diabetic retinopathy

PurposeTo determine the correlations among apoA-1, apoB, and apoB/A-1, the ratio of the first two and their relation to the severity of diabetic retinopathy (DR).MethodsA total of 116 patients with type 2 diabetes, 34 with nonproliferative diabetic retinopathy (NPDR) and 82 with proliferative diabetic retinopathy (PDR), were included. The serum levels of apoA-1, apoB, and the apoB/A-1 ratio were compared. We performed multiple regression analyses to determine whether age, diabetes duration, glycohemoglobin level, estimated glomerular filtration rate, body mass index, or hypertension contribute to PDR.ResultsThe apoB levels were lower in the NPDR group than in the PDR group (90.8 ± 21.4 versus 102.5 ± 25.3 mg/dl) (P = 0.02). The apoA-1 levels did not differ between the groups. The apoA-1 was lower in the PDR group than in the NPDR group (136.9 ± 24.9 versus 145.6 ± 21.2 mg/dl) mg/dl (P = 0.08). The apoB/A-1 ratio differed significantly between groups (NPDR versus PDR, 0.64 ± 0.20 versus 0.77 ± 0.24) (P = 0.004). Age, apoB/A-1, and diabetes duration were independent risk factors for PDR (R = −3.49, 3.06, and 2.44; standard regression coefficient, −0.33, 0.28, and 0.23; P = 0.0007, P = 0.003, and P = 0.02, respectively). The PDR group had significantly higher serum levels of apoB and apoB/A-1 than the NPDR group.ConclusionsThe apoB/A-1 ratio may contribute to PDR progression in patients with DR. High apoB and apoB/A-1 values may be related to PDR development.

Reproducibility of Neonate Ocular Circulation Measurements Using Laser Speckle Flowgraphy.

Measuring the ocular blood flow in neonates may clarify the relationships between eye diseases and ocular circulation abnormalities. However, no method for noninvasively measuring ocular circulation in neonates is established. We used laser speckle flowgraphy (LSFG) modified for neonates to measure their ocular circulation and investigated whether this method is reproducible. During their normal sleep, we studied 16 subjects (adjusted age of 34–48 weeks) whose blood flow could be measured three consecutive times. While the subjects slept in the supine position, three mean blur rate (MBR) values of the optic nerve head (ONH) were obtained: the MBR-A (mean of all values), MBR-V (vessel mean), and MBR-T (tissue mean), and nine blood flow pulse waveform parameters in the ONH were examined. We analyzed the coefficient of variation (COV) and the intraclass correlation coefficient (ICC) for each parameter. The COVs of the MBR values were all ≤10%. The ICCs of the MBR values were all >0.8. Good COVs were observed for the blowout score, blowout time, rising rate, falling rate, and acceleration time index. Although the measurement of ocular circulation in the neonates was difficult, our results exhibited reproducibility, suggesting that this method could be used in clinical research.

Comparison of surgical procedures for vitreous surgery in diabetic macular edema

PurposeResults of vitreous surgery alone in patients with diabetic macular edema (Vit group) were compared with results of surgery combined with peeling of the internal limiting membrane (ILM group), and surgery combined with removal of the residual vitreous cortex after its visualization using triamcinolone acetonide (TA) and a postoperative intravitreal TA injection (TA group). Visual acuities after the operation, degree of improvement in visual acuity (VA), and intra- and postoperative complications were evaluated.MethodsThe study included 141 consecutive patients (168 eyes) who could be followed up for at least 12 months after the operation. The Vit group consisted of 66 eyes, the ILM group of 62 eyes, and the TA group of 40 eyes. Patient background factors, and visual acuities 6 and 12 months after operation were evaluated first, and at the final examination, the degree of improvement in VA, the incidences of intra- and postoperative complications, and the incidence of intraocular pressure ≥25 mmHg were studied.ResultsPreoperative VA was compared with the 6- and 12-month postoperative VA and the VA at the final examination. The preoperative to 6 months postoperative improvements and those between the 12-month postoperative and final examination did not differ among the three groups. However, the degree of improvement in VA between 6 and 12 months after the operation was significantly smaller in the TA group than in the other two groups. The incidences of intra- and postoperative complications did not differ among the three groups, but the incidence of intraocular pressure ≥25 mmHg was slightly higher in the TA group.ConclusionSurgical results did not differ among the three operative techniques examined in this study.