Shuichiro Eguchi

Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema.

PURPOSE To investigate whether interleukin-6 (IL-6) or vascular endothelial growth factor (VEGF) is related to diabetic macular edema (DME) in subjects without posterior vitreous detachment (PVD). DESIGN Retrospective case-control study. PARTICIPANTS Twenty-six subjects who had DME without PVD and 12 subjects who had nondiabetic ocular disease (the control group). METHODS Vitreous fluid samples were obtained at vitreoretinal surgery, and the IL-6 and VEGF levels in vitreous fluid and plasma were measured by enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES Vitreous levels of IL-6 and VEGF in DME subjects without PVD. RESULTS The vitreous levels of both IL-6 and VEGF were significantly higher in the subjects with DME than in control subjects (P<0.0001 and P<0.0001, respectively). The vitreous level of IL-6 was significantly correlated with that of VEGF (P<0.0001). Vitreous levels of both IL-6 and VEGF were significantly higher in subjects with hyperfluorescent DME than in those with minimally fluorescent DME (P = 0.0008 and P = 0.0038, respectively). CONCLUSIONS We found that the levels of both IL-6 and VEGF were elevated in the vitreous fluid of subjects with hyperfluorescent DME. Our results suggest that IL-6 and VEGF may promote an increase of vascular permeability in DME subjects without PVD. Interleukin-6 may possibly induce an increase of vascular permeability through a paracrine effect on VEGF in these subjects.

Association of vitreous inflammatory factors with diabetic macular edema.

PURPOSE To evaluate the association between vitreous inflammatory factors and the severity of diabetic macular edema (DME). DESIGN Retrospective case-control study. PARTICIPANTS Fifty-three patients with DME, 15 patients with nondiabetic ocular disease, and 8 diabetic patients without retinopathy. METHODS Vitreous fluid samples were obtained during vitreoretinal surgery, and the levels of vascular endothelial growth factor (VEGF), intercellular adhesion molecule (ICAM)-1, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, and pigment epithelium-derived factor (PEDF) were measured by enzyme-linked immunosorbent assay. Multivariate analysis was performed to assess the association of these factors with the severity of DME. MAIN OUTCOME MEASURES Vitreous fluid levels of inflammatory factors. RESULTS Vitreous fluid levels of VEGF, ICAM-1, IL-6, and MCP-1 were significantly higher in patients with DME than in nondiabetic patients (P<0.05, all respectively) or diabetic patients without retinopathy (P<0.05, all respectively). In contrast, the PEDF level was significantly lower in patients with DME than in nondiabetic patients (P<0.05) or diabetic patients without retinopathy (P<0.05). Vitreous levels of VEGF, ICAM-1, IL-6, and MCP-1 were significantly higher in patients with hyperfluorescent DME than in those with minimally fluorescent DME (P = 0.0018, P = 0.0022, P = 0.0032, and P = 0.0053, respectively). Conversely, the vitreous level of PEDF was significantly lower in hyperfluorescent DME than in minimally fluorescent DME (P = 0.0134). Vitreous levels of VEGF, ICAM-1, IL-6, MCP-1, and PEDF were significantly correlated with the retinal thickness at the central fovea (P<0.0001, P<0.0001, P = 0.0282, P = 0.0009, and P = 0.0466, respectively). VEGF and ICAM-1 had a stronger influence on the severity of DME than the other factors (P = 0.0004 and P = 0.0372, respectively). CONCLUSIONS Vitreous fluid levels of VEGF, ICAM-1, IL-6, MCP-1, and PEDF were related to retinal vascular permeability and the severity of DME. VEGF and ICAM-1 had a stronger influence than the other factors. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any materials discussed in this article.

Non-contact, two-dimensional measurement of tissue circulation in choroid and optic nerve head using laser speckle phenomenon

A new apparatus has been developed using the laser speckle phenomenon for non-contact, two-dimensional analysis of tissue circulation in the choroid and optic nerve head (ONH). The fundus was illuminated by a diode laser spot and its image speckle was detected by an image sensor. The difference between the average of the speckle intensity (Imean) and the speckle intensity for successive scannings was calculated, and the ratio of Imean to this difference was defined as normalized blur (NB), which is a quantitative index of blood velocity. The results were displayed on color graphic monitors showing the two-dimensional variation of the NB level in the measurement field. In the rabbit, this apparatus was used to study the relationship between the results of NB measurement and the choroidal blood flow determined by the microsphere technique, the relationship between NB obtained from the ONH tissue free of visible surface vessels and the ocular perfusion pressure (OPP) after a lethal injection of pentobarital, and the effect of intraocular pressure (IOP) on the NB in the choroid or in the ONH. A stepwise reduction in the OPP was introduced by elevating the IOP manometrically. The relative decrease in the average NB over the field measured, NBav, in the choroid with the reduction in OPP showed a significant correlation with the relative change in the blood flow rate determined using the microsphere technique (r = 0.60, P < 0.001). NBav in the ONH had a good correlation with the OPP after a lethal injection of pentobarbital (r = 0.98, P < 0.001). NBav in the choroid decreased with reduction in the OPP. Although NBav in the ONH was little affected by OPP change when OPP was above 40 mmHg, at OPP levels below 40 mmHg, NBav in the ONH decreased along with a reduction in the OPP. These results suggest that by using the present apparatus, the blood velocity in the choroid or ONH under various conditions can be studied non-invasively in the living eye.

Quantitative analysis of regular and irregular astigmatism induced by pterygium.

PURPOSE To quantitatively evaluate the influence of pterygium and its removal surgery on both regular and irregular corneal astigmatism. METHODS In 19 eyes of 19 patients undergoing pterygium surgery, videokeratographic measurements were taken before and 1 month after surgery. Using Fourier harmonic analysis, dioptric data on mire rings were decomposed into spherical, regular astigmatism, and irregular astigmatism (decentration and higher order irregularity) components. The distance between the line of sight and the advancing edge of pterygium was measured, and the eyes were classified into two groups: large pterygium group (the distance <2.0 mm, n = 7) and small pterygium group (> or =2.0 mm, n = 12). Fifteen eyes of 15 subjects served as age-matched normal control eyes. RESULTS Before surgery, the magnitudes of regular astigmatism and higher order irregular astigmatism showed significant correlation with the size of pterygium. Regular astigmatism, asymmetry, and higher order irregularity in the large pterygium group were significantly greater than those of normal control eyes. The pterygium removal surgery significantly improved these changes, but regular astigmatism and higher order irregularity in the large pterygium group still remained significantly greater than those in the normal control eyes. CONCLUSION Pterygium induces a significant amount of regular and irregular astigmatism in proportion to its size. The removal surgery can improve these changes, but corneal distortion does not normalize completely in eyes with advanced pterygium.

Comparative study of intraoperative mitomycin C and beta irradiation in pterygium surgery.

AIMS To compare the rate of recurrence and complication after surgery for primary pterygium performed by one surgeon using either intraoperative mitomycin C or β irradiation. METHODS A retrospective study was performed of 164 eyes in 164 patients who had undergone primary pterygium surgery. After the pterygium was excised, the bare sclera was covered by sliding adjacent superior conjunctiva. 103 eyes received intraoperative mitomycin C (0.04%, 150 seconds) and 61 eyes β irradiation (total dose 21.6 Gy). The mean follow up period was 20.2 (SD 17.9) months (range 1–66 months). Recurrence was defined as the postoperative regrowth of fibrovascular tissue crossing the corneoscleral limbus. RESULTS The recurrence rate after mitomycin C and β irradiation was 8.74% and 23.0% of eyes, respectively, after mean follow up of 17.9 and 31.2 months, respectively. The Kaplan–Meier survival analysis revealed a significantly better outcome for those who had intraoperative mitomycin C (Mantel–Cox log rank analysis, p=0.031). The mean interval to recurrence was not significantly different between the two groups. During the follow up, none of the patients showed side effects or reactions related to mitomycin C or β irradiation. CONCLUSIONS The intraoperative administration of 0.04% mitomycin C is more effective than β irradiation as an adjunctive treatment for pterygium surgery in the patient population examined in this study.

Association of inflammatory factors with macular edema in branch retinal vein occlusion.

OBJECTIVE To evaluate the association between vitreous fluid levels of inflammatory factors and macular edema in patients with branch retinal vein occlusion (BRVO). METHODS In 39 patients with BRVO and macular edema and 21 individuals with idiopathic macular hole (MH) serving as controls, vitreous fluid samples were obtained during vitreoretinal surgery, and the levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor 2 (sVEGFR-2), soluble intercellular adhesion molecule 1 (sICAM-1), interleukin 6 (IL-6), monocyte chemotactic protein 1 (MCP-1), pentraxin 3 (PTX3), and pigment epithelium-derived factor (PEDF) were measured by enzyme-linked immunosorbent assay. Macular edema was examined by optical coherence tomography. RESULTS Vitreous fluid levels of sVEGFR-2, VEGF, sICAM-1, IL-6, MCP-1, and PTX3 were significantly higher in the patients with BRVO than in those with MH; however, the PEDF level was significantly lower in the BRVO group. Vitreous fluid levels of all 7 factors were significantly correlated with the retinal thickness at the central fovea. There were also significant correlations of sVEGFR-2 with sICAM-1, IL-6, MCP-1, and PTX3 but no correlation with VEGF. However, there were significant correlations of VEGF with sICAM-1, IL-6, MCP-1, and PEDF in the BRVO group. CONCLUSIONS Vitreous fluid levels of sVEGFR-2, VEGF, sICAM-1, IL-6, MCP-1, PTX3, and PEDF are strongly correlated with retinal vascular permeability and the severity of macular edema in patients with BRVO. These findings may be useful for understanding macular edema and developing new treatments for BRVO.

Creating cataract in a pig eye.

The purpose of this study was to create a uniform, reproducible hardened lens nucleus and an anterior capsule in a pig eye that approximate those in the human eye for use in cataract surgery training. The lens nuclei was hardened and anterior capsule elasticity was reduced in pig eyes by injecting the lens with mixtures of formalin and alcohol (ethanol, 2-propanol, or both). A 30 gauge needle was used to pierce the lens 3.0 mm from the limbus. Then, 0.2 mL of the formalin and alcohol mixture was injected. The most effective mixture was formalin, ethanol, and 2-propanol in the ratio 4:3:3. Fifteen minutes after this mixture was injected, the pig eye had nuclear cataract with grade III hardness and an anterior capsule that approximated the capsule in a human cataractous eye. The cataract created by this method will be useful in teaching continuous curvilinear capsulorhexis, divide and conquer and phaco chop phacoemulsification, and nuclear hydrodelineation and rotation.

Analysis of liquid accumulated in the distended capsular bag in early postoperative capsular block syndrome

PURPOSE To analyze the transparent liquid between the posterior lens capsule and the posterior chamber intraocular lens (PC IOL) in early postoperative capsular block syndrome and discuss the mechanism of posterior capsule distention. SETTING Department of Ophthalmology, Tokyo University School of Medicine, and Tokyo Research Institute, Seikagaku Corporation, Tokyo, Japan. METHODS This study evaluated 3 cases of capsular block syndrome presenting with transparent liquid in the distended capsular bag 1 day after cataract surgery. The transparent liquid material between the posterior capsule and PC IOL was aspirated and analyzed using high-performance liquid chromatography (HPLC). Also, sodium hyaluronate was diluted using a dialyzer to determine whether the aqueous humor was drawn into the capsular bag by an osmotic gradient across the capsule. RESULTS The elution time of the samples was almost the same as that of sodium hyaluronate 1.0% (Healon) The concentration of the samples ranged from 3.29 to 9. 01 mg/mL by HPLC analysis. The sodium hyaluronate absorbed the physiological salt solutions through the dialyzer and expanded to 1. 9 times its original volume. CONCLUSIONS These results indicate that the main ingredient of the transparent liquid in capsular bags is sodium hyaluronate and that the distention is caused by aqueous humor being drawn into the capsular bag by an osmotic gradient across the capsule when the capsulorhexis diameter is smaller than that of the PC IOL and by viscoelastic material retained and trapped in the bag intraoperatively.

Effects of scleral buckling and encircling procedures on human optic nerve head and retinochoroidal circulation

AIMS To study the effects of segmental scleral buckling and encircling procedures on tissue circulation in the human optic nerve head (ONH) and choroid and retina. METHODS Using the laser speckle method, the normalised blur (NB) value, a quantitative index of tissue blood velocity, was measured every 0.125 seconds and averaged over three pulses in the optic nerve head (NBONH) and choroid and retina (NBch-ret) in 10 patients with unilateral rhegmatogenous retinal detachment (mean age 52 (SD 17)). NBONH, NBch-ret, and intraocular pressure (IOP) in both eyes, and blood pressure (BP) were measured before, and 1, 4, and 12 weeks after the scleral buckling and encircling procedure. RESULTS NBch-reton the buckled side was significantly reduced after surgery and smaller than that in the unoperated contralateral eye throughout the study period (ANOVA, p<0.0001). NBch-ret on the unbuckled side, in the foveal area, NBONH, IOP, and BP showed no significant change. CONCLUSIONS It was indicated that the segmental scleral buckling procedure with encircling elements decreased tissue blood velocity in the choroid and retina on the buckled side but caused no significant change on tissue circulation in other areas of the fundus or ONH.

Vitreous inflammatory factors in macular edema with central retinal vein occlusion

PurposeTo investigate the correlation of soluble intercellular adhesion molecule 1 (sICAM-1) and vascular endothelial growth factor (VEGF) with macular edema in patients with central retinal vein occlusion (CRVO).MethodsTwenty-nine patients who had CRVO with macular edema and 16 patients with non-ischemic ocular diseases (control group) participated. Retinal ischemia was evaluated by measuring the area of capillary non-perfusion with fluorescein angiography and the public domain Scion Image program. Macular edema was examined by optical coherence tomography. Vitreous samples were obtained during pars plana vitrectomy. VEGF and sICAM-1 levels in vitreous fluid and plasma were determined by enzyme-linked immunosorbent assay.ResultsThe median vitreous levels of VEGF and sICAM-1 were significantly higher in the CRVO patients than in the control group [366 vs. 15.6 pg/ml (P < 0.001) and 20.5 vs. 5.0 ng/ml (P < 0.001), respectively]. Vitreous levels of both VEGF and sICAM-1 were also significantly higher in the CRVO patients who had retinal ischemia than in those without ischemia (P < 0.001 and P = 0.011, respectively). Vitreous levels of VEGF and sICAM-1 were also significantly correlated with the severity of macular edema (P = 0.004 and P = 0.012, respectively).ConclusionsVEGF and sICAM-1 may both increase vascular permeability in CRVO patients with macular edema, with sICAM-1 acting together with and/or via VEGF.