[Association between age and chorioretinal hemodynamics in normal volunteers examined with laser speckle flowgraphy].

PURPOSE: To investigate the relationship between age and chorioretinal hemodynamics in normal volunteers examined with Laser speckle flowgraphy (LSFG-NAVI). SUBJECTS AND METHODS: 107 eyes of 107 healthy volunteers aged from 21 to 78 years old were included. Laser speckle flowgraphy measurements of relative blood velocity (mean blur rate: MBR), skewness in the wave of blood velocity (Skew) and blowout score (BOS), which indicates ease of blood flow, were obtained as parameters of chorioretinal hemodynamics. MBR and BOS were measured on the optic disc and macula, and BOS and Skew were measured in retinal arteries and veins. RESULTS: There was a negative correlation between age and MBR on the optic disc and macula. There was a negative correlation between age and BOS on the optic disc, macula, retinal arteries and retinal veins. CONCLUSION: There was a negative correlation between MBR, BOS and age in all measurement areas. MBR and BOS may serve as indexes for a new interpretation of fundus pathology including age-related arterial sclerosis.

Intravitreal injection of erythropoietin protects against retinal vascular regression at the early stage of diabetic retinopathy in streptozotocin-induced diabetic rats.

A single intravitreal injection of erythropoietin (EPO) (50 ng/eye) or phosphate-buffered saline was administered to 5-week-old Sprague-Dawley rats at the onset of diabetes mellitus (DM) to determine and evaluate the protective effect of EPO on retinal microvessels. DM was induced by an intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body weight). Morphological changes in microvessels in flat retinal preparations were evaluated during the subsequent 4 weeks by three-dimensional imaging of all blood vessels stained with fluorescein isothiocyanate-conjugated tomato lectin, following immunofluorescence techniques. No marked differences were observed in the shape or density of retinal vessels and the number of retinal capillary branches of the four groups [control, EPO, DM, and DM/EPO] up to 4 weeks after STZ administration. We also observed unique type IV collagen-positive filamentous structures that lacked both cellular elements and blood circulation (lectin-/type IV+ acellular strands), suggesting regressed vessel remnants. The lectin-/type IV+ acellular strands were detected soon after the onset of DM in the diabetic rats, and the number of these structures increased in the DM group (P < 0.01). A single intravitreal injection of EPO caused a significant reduction in the number of lectin-/type IV+ acellular strands to levels observed in the control group. However, the lectin-/type IV+ acellular strands were observed in the central area of the retina near the optic disc in all four groups. Intravitreal injection of EPO resulted in downregulation of the EPO receptor, vascular endothelial growth factor (VEGF), and VEGF receptor at 4 weeks. We conclude that EPO may play a primary role against the progression of diabetic retinopathy by reducing blood vessel degeneration at a very early disease stage.

Choroidal detachment after uncomplicated small incision cataract surgery.

BACKGROUND AND PURPOSE: Angioedema is a well-recognized side effect of angiotensin-converting enzyme inhibitors, but is rarely associated with angiotensin II receptor blockers (ARB). Here, we report the first case of a patient on ARB therapy (telmisartan) for hypertension who developed serous choroidal detachment localized to the posterior pole after sub-Tenon anesthesia for small incision cataract surgery. METHODS AND RESULTS: An 82-year-old Japanese woman who received oral medications for hypertension underwent cataract surgery with sub-Tenon anesthesia using 2% Xylocaine(®) on her left eye. Her corrected distance visual acuity improved to 20/25 on the first day after the surgery. On the fifth day, however, it decreased to 20/40 and choroidal detachment was detected at the posterior pole. We suspected an increase of choroidal vascular permeability and started oral steroid therapy. After 1 week, the area of detachment was smaller and her acuity improved to 20/20. Subsequently, she underwent cataract surgery without sub-Tenon anesthesia on her right eye, and no choroidal detachment occurred. CONCLUSION: This is the first published case of ARB-induced choroidal detachment after uncomplicated small incision cataract surgery. Sub-Tenon anesthesia may aggravate angioedema associated with ARB therapy, so ophthalmologists should be aware of this rare complication.

Macular microcirculation in patients with epiretinal membrane before and after surgery.

BACKGROUND: To investigate blood flow velocity (BFV) in the perifoveal capillaries before and after vitreous surgery for patients with epiretinal membrane (ERM). METHODS: Twenty-one eyes in patients with ERM and 16 eyes in healthy subjects were involved in this study. Fluorescein angiography was performed using a scanning laser ophthalmoscope and BFV was analyzed by the tracing method. Foveal thickness (FT) was measured by optical coherence tomography. RESULTS: BFV was significantly slower in the ERM patients (1.04 ± 0.10 mm/s) than in the healthy subjects (1.49 ± 0.11 mm/s ) (p = 0.0010). BFV in the ERM patients 6 months after vitreous surgery (6 M) (1.21 ± 0.02 mm/s) significantly increased compared with BFV before surgery (0 M) (1.04 ± 0.10 mm/s) (p = 0.0061). BFV 1 year after vitreous surgery (1 Y) significantly increased (1.38 ± 0.02 mm/s) compared with BFV(6 M) (1.21 ± 0.02 mm/s) (p = 0.0235). FT was significantly greater in the ERM patients (351.7 ± 87.1 µm) than in the healthy subjects (158.9 ± 16.9 µm) (p = 0.0011). FT (6 M) significantly decreased (285.3 ± 36.9 µm) compared with FT before surgery (0 M) (351.7 ± 87.1 µm) (p = 0.0212). FT did not show significant differences between (6 M) and (1 Y). No significant correlation was found between BFV and FT before surgery. CONCLUSIONS: Perifoveal capillary BFV in patients with ERM was slower than that in the healthy subjects, and significantly improved after vitreous surgery as time progressed. It can be said that perifoveal capillary BFV is related to the development and improvement of ERM in the long term.

Multicenter randomized clinical trial of retinal photocoagulation for preproliferative diabetic retinopathy.

PURPOSE: To evaluate the effectiveness of selective photocoagulation (S-PC) for nonperfusion areas (NPA) in preproliferative diabetic retinopathy (PPDR). SUBJECTS AND METHODS: A multicenter randomized controlled clinical trial of 69 patients with PPDR showing NPA comparable to or larger than those on reference photographs. The patients were assigned to 2 groups; one was treated with S-PC (PC group: 32 patients), while the other did not receive S-PS (non-PC group: 37 patients). In the non-PC group, panretinal photocoagulation (PRP) was performed whenever proliferative diabetic retinopathy (PDR) developed. In the PC group, S-PC of the NPA was performed followed by additional coagulation whenever the NPA extended, and PRP was performed whenever PDR developed. The primary outcome was the development of PDR. RESULTS: During the entire course, PDR developed in 18 (26%) of the 69 patients. The incidence was significantly higher in the non-PC group than in the PC group. Comparison of the visual acuity at the time of registration and after 36 months showed no significant differences between the two groups. CONCLUSIONS: S-PC for NPA in PPDR is effective at preventing PDR development.

Soluble vascular endothelial growth factor receptor-2 and inflammatory factors in macular edema with branch retinal vein occlusion.

PURPOSE: To investigate relationships among vitreous fluid levels of soluble vascular endothelial growth factor receptor-2 (sVEGFR-2), vascular endothelial growth factor (VEGF), and soluble intercellular adhesion molecule 1 (sICAM-1) in patients with branch retinal vein occlusion (BRVO) and macular edema or patients with idiopathic macular hole. DESIGN: Retrospective case-control study. SETTING: Tokyo Women's Medical University and Eguchi Eye Hospital. PATIENT POPULATION: Forty-nine Japanese patients who underwent unilateral vitrectomy (27 with BRVO and 22 with macular hole). OBSERVATION PROCEDURES: Vitreous fluid samples were obtained during vitreoretinal surgery to measure the levels of sVEGFR-2, VEGF, and sICAM-1. Retinal ischemia was evaluated from capillary nonperfusion on fluorescein angiography. Macular edema was examined by optical coherence tomography. MAIN OUTCOME MEASURES: Vitreous fluid levels of the 3 molecules and severity of macular edema. RESULTS: BRVO patients had a significantly higher vitreous fluid level of sVEGFR-2 (median, 1670 pg/mL; interquartile range [IQL], 1205 to 2225 pg/mL) than macular hole patients (median, 1265 pg/mL; IQR, 731 to 1800 pg/mL; P = .017), as was the case for VEGF (median, 237 pg/mL; IQR, 42.2 to 1305 pg/mL; vs median, 15.6 pg/mL; IQR, 15.6 to 15.6 pg/mL; P < .001) and sICAM-1 (median, 10.1 ng/mL; IQR, 6.3 to 22.5 ng/mL; vs median, 4.1 ng/mL; IQR, 3.3 to 6.0 ng/mL; P < .001). In BRVO patients, there was a significant positive correlation between vitreous fluid levels of sVEGFR-2 or VEGF and sICAM-1, but not between sVEGFR-2 and VEGF. Vitreous fluid levels of all 3 molecules were correlated significantly the with severity of macular edema in BRVO patients. CONCLUSIONS: sVEGFR-2 may induce an increase of vascular permeability together with or via sICAM-1, or both with and via sICAM-1, in BRVO patients with macular edema.

Chronic refractory uveitis in a patient with childhood-onset cyclic neutropenia.

We report a rare case of chronic refractory uveitis in a patient with childhood-onset cyclic neutropenia (CN). A 19-year-old woman, who had a history of CN beginning at age 2, presented with bilateral chronic nongranulomatous uveitis, complicated cataract, retinal vasculitis, cystoids macular edema, and vitreous hemorrhage. She had recurrent episodes of oral ulcers, tonsillitis, genital ulcers, and folliculitis during neutropenic nadir. After the resumption of granulocyte colony-stimulating factor therapy for her CN, vitreous hemorrhage in both eyes followed. Her eyes were treated with topical corticosteroids, retinal photocoagulation, and cataract surgery. Blood and bone marrow test results confirmed the diagnosis of CN. She also fulfilled the diagnostic criteria of Behçet's disease, though clinical features of her uveitis were dissimilar to those found in that disease.

Vitreous inflammatory factors in macular edema with central retinal vein occlusion.

PURPOSE: To 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). METHODS: Twenty-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. RESULTS: The 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). CONCLUSIONS: VEGF and sICAM-1 may both increase vascular permeability in CRVO patients with macular edema, with sICAM-1 acting together with and/or via VEGF.

Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in macular edema with central retinal vein occlusion.

PURPOSE: To investigate whether pigment epithelium-derived factor (PEDF) or vascular endothelial growth factor (VEGF) influences macular edema in patients with central retinal vein occlusion (CRVO). MATERIALS AND METHODS: In 27 patients who had CRVO with macular edema and 21 patients with nonischemic ocular diseases (control group), retinal ischemia was evaluated by measuring the area of capillary nonperfusion on fluorescein angiography and macular edema was examined by optical coherence tomography. Vitreous fluid samples were obtained during pars plana vitrectomy. RESULTS: The vitreous level of VEGF was significantly higher in the CRVO patients than in the controls (median: 366 vs. 15.6 pg/ml, P < 0.0001), while the vitreous level of PEDF was significantly lower in the patients than in the controls (median: 17.5 vs. 28.4 ng/ml, P = 0.0298). Vitreous levels of VEGF were significantly higher in CRVO patients with retinal ischemia than in those without ischemia (P < 0.0001), while PEDF levels did not show a significant difference. Vitreous levels of VEGF and PEDF were related to the retinal thickness at the central fovea (P = 0.0059 and P = 0.0308, respectively). CONCLUSIONS: VEGF and PEDF may independently influence retinal vascular permeability in CRVO patients with macular edema.

[Long-term outcome of vitrectomy combined with internal limiting membrane peeling for idiopathic macular holes].

PURPOSE: To elucidate the long-term outcome of internal limiting membrane (ILM) peeling on visual function during vitrectomy for idiopathic macular holes using scanning laser ophthalmoscope (SLO) microperimetry. DESIGN: Prospective uncontrolled study. PATIENTS AND METHODS: We studied 31 eyes (29 patients) with idiopathic macular holes. All patients underwent vitrectomy with ILM peeling. The SLO microperimetry was performed preoperatively, and once a year for 3 years postoperatively to detect scotomas in and around the macular holes, and both within and in close vicinity to the areas of ILM peeling. RESULTS: Closure of macular holes after one surgery was confirmed in all cases except for 2 with second surgery. The visual acuity by logarithmic minimum angle of resolution (logMAR) averaged 0.71 +/- 0.36 before surgery, 0.23 +/- 0.31 one year, 0.14 +/- 0.27 two years and 0.12 +/- 0.26 three years after surgery. There was significant improvement up to 2 years after the surgery. All scotomas detected before surgery in the holes, and 77.4% of those detected around the holes decreased gradually. No scotomas were detected in or around the area of ILM peeling either before or after surgery. CONCLUSION: ILM peeling in vitrectomy for idiopathic macular holes successfully improved visual acuity and did not influence retinal sensitivity in and around the area of ILM peeling. The scotomas detected in and around the holes before surgery gradually reduced or disappeared.

Use of the laser speckle flowgraphy in posterior fundus circulation research.

OBJECTIVE: To review articles aiming to present an overview of the principles, progress, uses and limitations of laser speckle flowgraphy (LSFG) in posterior fundus circulation research. DATA SOURCES: The data used in this review was obtained mainly from the studies reported in PubMed using the key terms "laser speckle", "ocular blood flowmetry" and "retinal imaging". STUDY SELECTION: Relevant literatures on studies of LSFG were selected. RESULTS: LSFG is a unique, noninvasive imaging instrument to quantitatively visualize posterior fundus circulation in vivo. This review delineates the LSFG principles and development, demonstrates its extensive applicability for measurement of retina, choroid and optic nerve head circulation, compares it with other retinal imaging technologies and discusses unresolved issues. CONCLUSIONS: LSFG is a noninvasive, two-dimensional objective diagnostic technique that has become a powerful method for the clinical and scientific assessment of posterior fundus circulation. Further studies may help to develop a more comprehensive evidence-based measurement and facilitate the correlation with other methods for chorioretinal circulation assessment.

Influence of macular microcirculation and retinal thickness on visual acuity in patients with branch retinal vein occlusion and macular edema.

PURPOSE: To investigate perifoveal capillary blood flow velocity and retinal thickness at the central fovea in patients with branch retinal vein occlusion (BRVO) and macular edema and to assess their relation with visual acuity and visual prognosis. METHODS: Eighteen patients with BRVO and 16 healthy volunteers were compared. Perifoveal capillary blood flow velocity was measured on fluorescein angiograms with a scanning laser ophthalmoscope by the tracing method. Retinal thickness was measured at the central fovea by optical coherence tomography. Best-corrected visual acuity (BCVA) was determined. RESULTS: BCVA differed significantly between patients and controls (P < 0.0001). Among patients, BCVA was negatively correlated with perifoveal capillary blood flow velocity by univariate analysis (r = -0.7916, P < 0.0001), and positively correlated with retinal thickness at the central fovea (r = 0.8970, P < 0.0001). Multivariate analysis showed that retinal thickness at the central fovea was the only independent determinant of BCVA (P < 0.0001). CONCLUSIONS: In patients with BRVO, BCVA was more strongly influenced by retinal thickness at the central fovea than by perifoveal capillary blood flow velocity.

[Pathogenesis of macular edema associated with branch retinal vein occlusion and strategy for treatment].

We summarize the pathogenesis and the treatment strategy for macular edema in patients with branch retinal vein occlusion (BRVO), focusing on the role of the cytokines. Various cytokines are involved in the pathogenesis of macular edema associated with BRVO. When BRVO occurs, it leads to retinal ischemia that induces the production of cytokines such as vascular endothelial growth factor (VEGF) by retinal cells such as glial cells and vascular endothelial cells in the occluded region affected by anoxia. These cytokines interact with each other (cytokine network) and this results in impairment of the blood-retinal barrier and an increase of vascular permeability, considered important in the development of macular edema associated with BRVO. Treatment for this condition includes triamcinolone acetonide, anti-VEGF antibody, laser therapy and vitrectomy, all of which lead to the suppression of cytokine production. To manage macular edema associated with BRVO, it is important to control cytokine production with a combination of treatments.

Pigment epithelium-derived factor and vascular endothelial growth factor in branch retinal vein occlusion with macular edema.

BACKGROUND: We investigated whether pigment epithelium-derived factor (PEDF) or vascular endothelial growth factor (VEGF) influence macular edema in patients with branch retinal vein occlusion (BRVO). This investigation aimed to clarify the influence of PEDF in the vitreous fluid on retinal vascular permeability in patients with macular edema secondary to BRVO. The findings were expected to be useful for the treatment of macular edema in BRVO patients. METHODS: This was a retrospective cross-sectional comparative case series. Thirty-three BRVO patients with macular edema and 24 control patients with nonischemic ocular diseases were enrolled. Retinal ischemia was evaluated by measuring the area of capillary nonperfusion on fluorescein angiography with Scion Image software. Macular edema was examined by optical coherence tomography. Vitreous fluid samples were obtained via pars plana vitrectomy, and the VEGF and PEDF levels were determined by enzyme-linked immunosorbent assay. RESULTS: The vitreous level of VEGF was significantly higher in BRVO patients than controls (P < 0.001). The vitreous PEDF level was significantly lower in BRVO patients than controls (P = 0.026). In BRVO patients, vitreous levels of PEDF and VEGF showed a significant negative correlation with each other (P < 0.001). Additionally, the vitreous VEGF level had a significant positive correlation (P < 0.001) and the vitreous PEDF level had a significant negative correlation (P < 0.001) with the nonperfused retinal area in BRVO patients. Furthermore, vitreous levels of VEGF and PEDF showed significant positive (P = 0.001) and negative (P = 0.014) correlations, respectively, with macular edema in BRVO patients. CONCLUSIONS: VEGF and PEDF may inversely influence retinal vascular permeability in patients with ischemic BRVO and macular edema. However, prospective validation will be needed to confirm these observations.

[Case of traumatic chiasmal syndrome].

BACKGROUND: Traumatic neuropathy of the optic chiasm is a rare finding which occurs after severe blunt head trauma. It is often accompanied by dysfunction of the pituitary gland and hypothalamus and called traumatic chiasmal syndrome. We report a patient with traumatic chiasmal syndrome caused by a severe traffic accident. CASE: A 25 year-old woman was referred for bitemporal visual field defects caused by a traffic accident two months before. Corrected visual acuity was 0.05 in the right eye and 1.2 in the left eye. Bilateral optic atrophy and relative afferent pupillary defect in the right eye were found. Magnetic resonance imaging revealed an enlarged optic chiasm. Computed tomography disclosed many fractures in the skull including the back wall of the sphenoid sinuses. She also suffered from diabetes insipidus and anosmia. CONCLUSION: Traumatic optic neuropathy of the optic chiasm is a rare condition which can be differentiated from neuropathy in the optic canal by considering the patterns of visual field defects and their accompanying signs.

[Strategy for treatment of diabetic retinopathy].

This paper conducts an analysis and discussion of the pathogenesis and treatment strategies for diabetic retinopathy, a major cause of blindness. Histological examination of experimental and biopsied material found that the pericyte necrosis and basement membrane thickening were responsible for sclerosis of retinal microvessels. The macrophages were noted in the pathogenesis of retinopathy. The cytokines of intraocular fluid were analyzed, and the vascular endothelial growth factor and intercellular adhesion molecule-1 were found to be closely related to retinopathy and macular edema. These findings suggest that the inflammation lead to the complex pathology of retinopathy. Anti-inflammatory drugs need to be included in the therapeutic strategy. The Diabetic Eye Notebook is an important source of information for patients who were lost to followup.