Dilation of porcine retinal arterioles to nobiletin, a polymethoxyflavonoid: Roles of nitric oxide and voltage-dependent potassium channel.

We examined the effects of nobiletin, a polymethoxyflavonoid, on the retinal microvascular diameter to determine if they depend on the endothelium and/or smooth muscle to reveal the signaling mechanisms involved in this vasomotor activity. Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Video microscopic techniques recorded diametric responses to nobiletin. The retinal arterioles dilated in a nobiletin concentration-dependent (100 pM-10 µM) manner and decreased by 50% after endothelial removal. The nitric oxide (NO) synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), reduced nobiletin-induced vasodilation comparable to denudation. Blockade of soluble guanylyl cyclase by 1H-[1,2,4] oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) produced a similar inhibitory effect as that by L-NAME. Nobiletin-induced vasodilation was also inhibited by the nonselective potassium channel inhibitor, tetraethylammonium (TEA), and the voltage-gated K (Kv) inhibitor, 4-aminopyridine. Co-administration of L-NAME and TEA almost eliminated nobiletin-induced vasodilation. Nobiletin elicits both endothelium-dependent and -independent dilation of retinal arterioles mediated by NO release and Kv channel activation, respectively.

Long-Term Follow-Up Changes of Central Choroidal Thickness Thinning after Repeated Anti-VEGF Therapy Injections in Patients with Central Retinal Vein Occlusion-Related Macular Edema with Systemic Hypertension.

PURPOSE: We investigated the thinning of central choroidal thickness (CCT) following intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs to treat central retinal vein occlusion (CRVO)-related macular edema in patients with and without systemic hypertension (HT) to assess the influence of repeated anti-VEGF therapy and HT on the choroid in CRVO eyes. METHODS: We conducted a retrospective study involving 27 patients with CRVO-related macular edema from January 2014 to July 2017, with follow-ups exceeding 18 months. Visual acuity (VA), central retinal thickness (CRT), and CCT were evaluated before and after initial anti-VEGF drug treatment during follow-up. RESULTS: The mean follow-up period was 35.2 months. Seventeen (63.0%) patients had HT. At 1 month after treatment, VA had improved in 21 (77.8%) patients, and CRT had decreased in 25 (92.6%). At the final visit, 22 (81.5%) showed improved VA, 19 (70.4%) had resolved macular edema, and the CCT had gradually become thinner with additional drug injections in all the patients. Furthermore, the mean CCT in HT patients (209.0 µm) was significantly lower than in non-HT patients (256.1 µm), and the mean injections were 7.8 and 5.3, respectively (p = 0.2067). CONCLUSION: The CCTs were thinner in eyes with HT than in eyes without HT both before and after the repeated anti-VEGF injections.

Cotton Wool Spots after Anti-Vascular Endothelial Growth Factor Therapy for Macular Edema Associated with Central Retinal Vein Occlusion.

PURPOSE: To report a case series, whereby we encountered a transient increase in retinal cotton wool spots (CWS) following anti-vascular endothelial growth factor (anti-VEGF) therapy for the treatment of macular edema secondary to central retinal vein occlusion (CRVO). METHODS: Eighteen eyes were treated with intravitreal aflibercept (IVA), and 5 were treated with intravitreal ranibizumab (IVR). Fundus photographs obtained 1 month after initial IVA or IVR injections were retrospectively evaluated for the presence of CWS. RESULTS: Twenty-one (91.3%) patients had the following systemic diseases: hypertension, diabetes mellitus without retinopathy, dyslipidemia, or chronic renal failure requiring dialysis. One month after treatment, reduced macular edema was observed in 21 (91.3%) eyes. Initial injections facilitated complete resolution in 14 eyes, and CWS gradually became fainter with additional injections. CONCLUSION: Some eyes with CRVO-related macular edema can show a transient increase in CWS after initial anti-VEGF therapy; however, macular edema, retinal hemorrhage, and visual acuity were improved in almost every case.

Impairment of flicker-induced increase in retinal blood flow in diabetic pigs.

PURPOSE: To evaluate retinal blood flow (RBF) regulation in response to RBF stress in maturity-onset diabetes of the young type 3 (MODY3) pigs. STUDY DESIGN: Case-control study. METHODS: MODY3 pigs (diabetes mellitus [DM] group, n = 8) transfected with the human mutant hepatocyte nuclear factor-1⍺ and normal pigs of the same age (normal group, n = 8) were used as subjects. After confirming DM onset, the experiment was performed under inhalation anesthesia with isoflurane at 2 months of age before the cataract progressed. Ocular blood flow was assessed by calculating the optic papillary mean blur rate using laser speckle flowgraphy, modified for pig eye measurements. After baseline ocular blood flow measurements, flicker stimulation (12 Hz, 3 min) was applied, and ocular blood flow was measured over time. RESULTS: Blood glucose was 81.8 ± 5.1 mg/dL in the normal group and 311.4 ± 23.1 mg/dL in the DM group (mean ± standard error). The percent change in ocular blood flow at 3 min after flicker stimulation was +31.0 ± 10.9% in the normal group and -6.6 ± 6.5% in the DM group compared to the preload value, and the difference was statistically significant (Mann-Whitney test, P = 0.015). CONCLUSION: RBF response to flicker stimulation is reduced at 2 months of age in MODY3 pigs, suggesting that retinal neurovascular coupling is impaired from the early onset of DM.

Association of electroretinogram and morphological findings in branch retinal vein occlusion with macular edema.

The objective of this study is to evaluate the relations among electroretinogram parameters (cone a-wave, cone b-wave, and 30-Hz flicker), retinal thickness, and retinal volume in patients with branch retinal vein occlusion (BRVO) and macular edema. We prospectively examined 33 patients (33 eyes) with BRVO and macular edema. The amplitude and implicit time of the a-wave cone, b-wave cone, and 30-Hz flicker were calculated automatically from the ERG. Retinal thickness and volume were measured by optical coherence tomography (OCT) in nine macular subfields. Then, correlations between the ERG parameters and morphological parameters were analyzed. The 30-Hz flicker amplitude was significantly smaller in the eyes with BRVO and macular edema than in the unaffected contralateral eyes. Thirty-hertz flicker and cone b-wave implicit times were significantly longer in the eyes with macular edema than in the unaffected eyes. The implicit time of the cone b-wave was correlated with both retinal thickness and retinal volume in the temporal subfields. Thirty-hertz flicker amplitude was correlated with both retinal thickness and volume in the temporal and superior outer (site of occlusion) subfields, while 30-Hz flicker implicit time was correlated with retinal thickness and volume in the outer temporal subfield. Multiple regression analysis demonstrated that the retinal thickness and volume of the temporal subfields were significant "determinants" of the implicit time for the cone b-wave and 30-Hz flicker, as well as the 30-Hz flicker amplitude. These findings suggest that OCT parameters of the temporal region may reflect postreceptoral cone pathway function in BRVO patients with macular edema.

Functional-morphologic correlates in patients with branch retinal vein occlusion and macular edema.

PURPOSE: To investigate the relations among best-corrected visual acuity, retinal sensitivity, retinal thickness, and retinal volume in patients with branch retinal vein occlusion, and macular edema. METHODS: In 49 consecutive patients with branch retinal vein occlusion (mean age, 68.2 ± 9.9 years; 25 women and 24 men), macular function was documented by microperimetry and best-corrected visual acuity was determined on the logarithm of the minimum angle of resolution scale. Retinal thickness and retinal volume were measured by optical coherence tomography, and mean retinal sensitivity was calculated for each of nine macular subfields on the retinal map obtained by optical coherence tomography. Pearson correlation coefficients were calculated and multiple linear regression analysis was performed with 7 variables (age, gender, hypertension, hyperlipidemia, duration of branch retinal vein occlusion, nonperfused retinal area, and serous retinal detachment). RESULTS: On multivariate analysis, best-corrected visual acuity was significantly correlated with both retinal thickness and volume in 4 of 9 retinal subfields (fovea, superior inner, inferior outer, and nasal inner). In contrast, retinal sensitivity was correlated with both retinal thickness and volume in all 9 retinal subfields. CONCLUSION: Retinal thickness and retinal volume are more closely associated with retinal sensitivity than with best-corrected visual acuity. Measurement of retinal sensitivity may be useful for assessing branch retinal vein occlusion patients with macular edema.

[Case of retinal ischemia and retinal arteritis secondary to intravitreal nuclear drop].

BACKGROUND: A rare case of retinal arteritis and retinal ischemia as an incomplete branch retinal artery occlusion is reported following dropped lens fragments into the vitreous body. CASE: A 69 year-old-woman had a cataract OD with corrected visual acuity of 0.4. When she underwent phacoemulsification on March 11, the posterior capsule was damaged and nucleus fragments dropped into a vitreous body. A few days later, the vitreous opacity increased. The corrected visual acuity OD dropped to 0.06 due to anterior chamber inflammation and the intraocular pressure increased to 26 mmHg. During a pars plana vitrectomy on May 7, some retinal whitening were observed and incomplete branch retinal artery occlusion was confirmed by fluorescence fundus angiography. The corrected visual acuity finally improved to 0.3, but the right visual field defect remained. CONCLUSION: Incomplete branch retinal artery occlusion caused by phacoanaphylactic endophthalmitis secondary to lens fragments in the vitreous cavity seems to be a rare condition related to retinal whitening. The timing of pars plana vitrectomy should be considered before retinal arterial sheathing or retinal whitening can be noted.

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.

Aqueous humor levels of vasoactive molecules correlate with vitreous levels and macular edema in central retinal vein occlusion.

PURPOSE: Aqueous levels of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) are associated with the severity of macular edema in patients with central retinal vein occlusion (CRVO). We investigated whether aqueous and vitreous levels of these molecules were correlated in CRVO patients. METHODS: Aqueous and vitreous samples were obtained during cataract surgery and vitreous surgery from 17 patients (17 eyes) with CRVO and macular edema. The levels of VEGF and IL-6 in aqueous humor, vitreous fluid, and plasma were determined by enzyme-linked immunosorbent assay. RESULTS: The aqueous levels of VEGF and IL-6 were significantly correlated with the vitreous levels of these molecules (rho=0.8799, p=0.0004 and rho=0.8088, p=0.0012, respectively). Vitreous levels of VEGF and IL-6 were significantly higher in CRVO patients with retinal ischemia than in those without ischemia (p=0.0013 and p=0.0009, respectively), as were the aqueous levels of VEGF and IL-6 (p=0.0026, p=0.0120, respectively). Furthermore, both the aqueous and vitreous levels of VEGF and IL-6 were significantly correlated with the severity of macular edema (rho=0.7181, p=0.0041; rho=0.8260, p=0.0010; rho=0.5564, p=0.0260; and rho=0.6599, p=0.0039, respectively). CONCLUSIONS: Our results suggest that aqueous levels of VEGF and IL-6 may reflect the vitreous levels of these molecules. Measurement of VEGF and IL-6 in the aqueous humor may be clinically useful to assess the severity of macular edema in patients with CRVO.

[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.

Subarachnoid hemorrhage-negative Terson syndrome after intracranial artery treatment with a flow diverter device.

PURPOSE: To report a case of subarachnoid hemorrhage-negative Terson syndrome following intracranial artery treatment with flow diverter stents. OBSERVATIONS: A 40-year-old Asian woman presented with floaters in her right eye after treatment of an intracranial aneurysm with flow diverter stents. Vitreous hemorrhage and sub-inner limiting membrane (sub-ILM) hemorrhage were present in her right eye. On fluorescein angiography, contrast perfusion and vascular occlusion were not noted. Magnetic resonance imaging (MRI) did not show any evidence of subarachnoid hemorrhage (SAH). We hypothesize that the bleeding was due to Terson syndrome associated with intracranial treatment with the flow diverter stents. During follow-up, the vitreous hemorrhage and sub-ILM hemorrhage disappeared, and the floaters in her vision improved. CONCLUSIONS AND IMPORTANCE: This is the first reported case of vitreous hemorrhage and sub-ILM hemorrhage that should be considered to be Terson syndrome, after flow diverter stents treatment in the absence of SAH.

Vitreous levels of interleukin-6 and vascular endothelial growth factor in macular edema with central retinal vein occlusion.

OBJECTIVE: To investigate whether interleukin (IL)-6 or vascular endothelial growth factor (VEGF) influences macular edema in patients with central retinal vein occlusion (CRVO). DESIGN: Retrospective case-control study. PARTICIPANTS: Twenty-seven patients who had macular edema with CRVO and 16 patients with nonischemic ocular diseases (control group). METHODS: Retinal ischemia was evaluated by measuring the area of capillary nonperfusion using fluorescein angiography and the public domain Scion Image program, and macular edema was examined by optical coherence tomography. Vitreous fluid samples were obtained at pars plana vitrectomy. VEGF and IL-6 levels in vitreous fluid and plasma were determined with enzyme-linked immunosorbent assay kits. MAIN OUTCOME MEASURES: Vitreous fluid levels of IL-6 and VEGF. RESULTS: The vitreous fluid levels of VEGF (median: 435 pg/ml) and IL-6 (median: 51.2 pg/ml) were significantly higher in the patients with CRVO than in the control group (median: 62.4 pg/ml and 1.07 pg/ml, respectively; P = 0.0046 and P<0.0001, respectively). The vitreous fluid level of VEGF was significantly correlated with that of IL-6 (P = 0.0029). Vitreous fluid levels of both VEGF and IL-6 were significantly higher in patients with CRVO who had retinal ischemia than in those without ischemia (P<0.0001 and P = 0.0003, respectively). Vitreous fluid levels of VEGF and IL-6 were also significantly correlated with the severity of macular edema (P = 0.0014 and P = 0.0047, respectively). CONCLUSIONS: Both IL-6 and VEGF were elevated in the vitreous fluid of patients with ischemic CRVO and macular edema. VEGF may increase vascular permeability in patients with macular edema and CRVO, whereas IL-6 may also contribute by acting together with or via VEGF. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Macular autofluorescence in eyes with cystoid macula edema, detected with 488 nm-excitation but not with 580 nm-excitation.

BACKGROUND: Fundus autofluorescence (AF) derives from lipofuscin in the retinal pigment epithelium (RPE). Because lipofuscin is a by-product of phagocytosis of photoreceptors by RPE, AF imaging is expected to describe some functional aspect of the retina. In this study we report distribution of AF in patients showing macular edema. METHODS: Three eyes with diabetic macular edema (DME) and 11 with retinal vein occlusion (RVO), associated with macular edema (ME) were examined. ME was determined by standard fundus examination, fluorescein angiography (FA) and optical coherence tomography (OCT). AF was recorded using a Heidelberg confocal scanning laser ophthalmoscope (cSLO) with 488 nm laser exciter (488 nm-AF), and a conventional Topcon fundus camera with halogen lamp exciter and 580 nm band-pass filter (580 nm-AF). Color fundus picture, FA image and these two AF images were analyzed by superimposing all images. RESULTS: All subjects presented cystoid macular edema (CME) with petaloid pattern hyperfluorescence in FA. In 488 nm-AF, all eyes (100%) showed macular autofluorescence of a similar shape to that of the CME in FA. In contrast, in 580 nm-AF only one eye (7%) presented this corresponding petaloid-shaped autofluorescence. In all cases, peripheral retinal edemas did not show autofluorescence corresponding to the leakage in FA. CONCLUSIONS: In eyes with CME, analogous hyperautofluorescence to the CME was always observed in 488 nm-AF, while it was rarely observed in 580 nm-AF. Moreover, this CME hyperautofluorescence was only seen in the macular area. We hypothesize that autofluorescence from CME may be considered as a "pseudo" or "relative" autofluorescence, due to macular stretching following CME that may result in lateral displacement of macular pigments (MPs) and subsequent reduction of MPs density, as MPs block 488 nm-AF more intensely than 580 nm-AF. Although this phenomenon may not directly indicate change of RPE function, it may be used as a method to assess or track CME non-invasively.

The effect of topical diclofenac on choroidal blood flow in early postoperative pseudophakias with regard to cystoid macular edema formation.

PURPOSE: To study the chronological change in choroidal blood flow (ChBFlow), disruption of the blood-aqueous barrier, and incidence of cystoid macular edema (CME) in early postoperative pseudophakic eyes, as well as the effect of nonsteroidal anti-inflammatory drug (NSAID) eye drops on these phenomena. METHODS: Fifty patients who underwent phacoemulsification and foldable intraocular lens (IOL) implantation were randomized to receive either topical diclofenac or fluorometholone for 5 postoperative weeks. An additional 20 subjects, with long-standing pseudophakia served as the control. The blood-aqueous barrier was examined by laser flarimetry and choroidal blood velocity (ChBVel), volume (ChBVol), and ChBFlow by laser Doppler flowmetry (LDF) at 2 days and 1, 2, and 5 weeks after surgery. The incidence and severity of CME were evaluated by fluorescein angiography at 2 and 5 weeks after surgery. RESULTS: Compared with patients taking diclofenac, those receiving fluorometholone showed significantly reduced ChBVol at 2 weeks (0.38 +/- 0.08 vs. 0.32 +/- 0.07, P = 0.022) and ChBFlow at 1 (11.01 +/- 1.74 vs. 9.35 +/- 1.51, P = 0.003) and 2 (11.15 +/- 1.43 vs. 8.47 +/- 1.27, P = 0.000) weeks after surgery, as well as a significantly elevated amount of anterior flare at 1 (8.9 +/- 2.2 vs. 24.4 +/- 18.9, P = 0.001) and 2 (9.2 +/- 3.5 vs. 16.7 +/- 12.3, P = 0.025) weeks after surgery. The ChBVol and ChBFlow in the fluorometholone group, however, returned to normal and was not different from the diclofenac group at 5 weeks after surgery. The incidence of fluorescein angiographic CME trended to be higher (P = 0.08) at 2 weeks and was significantly higher (P = 0.001) at 5 weeks after surgery in eyes with fluoromethalone than with diclofenac. CONCLUSIONS: Reduction of ChBFlow, disruption of the blood-aqueous barrier, and incidence of CME in early postsurgical pseudophakic eyes were more effectively prevented chronologically in eyes treated with diclofenac than in those treated with fluorometholone.

Relationship of macular microcirculation and retinal thickness with visual acuity in diabetic macular edema.

PURPOSE: To assess perifoveal capillary blood flow velocity (BFV), capillary occlusion, and retinal thickness at the central fovea in diabetic patients with or without clinically significant macular edema; to examine the relationships of these variables with visual acuity (VA); and to identify their contributions to visual outcome and diabetic macular edema. DESIGN: Comparative cross-sectional prospective study. PARTICIPANTS AND CONTROLS: Diabetic patients with clinically significant macular edema (CSME) (n = 22), matched diabetic patients without CSME (n = 22), and healthy volunteers (n = 16). METHODS: Capillary BFV was measured by fluorescein angiography using a scanning laser ophthalmoscope and was analyzed by the tracing method. Severity of perifoveal capillary abnormalities was classified by the size and outline of the foveal avascular zone (FAZ) and extent of foveal capillary loss. Macular thickness was measured by optical coherence tomography. Each subject underwent a complete ophthalmic evaluation, and best-corrected VA (BCVA) was converted to the logarithm of the minimum angle of resolution scale. MAIN OUTCOME MEASURES: Relationship of perifoveal capillary BFV, capillary occlusion, and foveal thickness with VA. RESULTS: Best-corrected VA significantly differed among all 3 groups (P<0.0001). Best-corrected VA correlated negatively with BFV (r = -0.644, P<0.0001) among all subjects and positively with retinal thickness at the central fovea in diabetic patients with CSME (r = 0.640, P = 0.0013). There was a positive correlation between BCVA and severity in the size of the FAZ (r = 0.484, P = 0.0015), outline of the FAZ (r = 0.542, P = 0.0004), and extent of foveal capillary loss (r = 0.585, P = 0.0001) among all diabetic subjects. Multiple regression analysis showed that retinal thickness at the central fovea was the only variable that significantly predicted VA (standardized regression coefficient, 0.635; P = 0.0001). CONCLUSIONS: Best-corrected VA was associated with perifoveal capillary BFV, severity of perifoveal capillary occlusion, and retinal thickness at the central fovea in diabetic patients, but the greatest contributing factor was only the retinal thickness.

[Quantification of metamorphopsia in the course of branch retinal vein occlusion with M-CHARTS].

PURPOSE: To evaluate visual function disorder in patients with branch retinal vein occlusion by quantifying the degree of metamorphopsia. DESIGN: prospective interventional case series. SUBJECTS AND METHODS: The subjects were 12 patients(12 eyes) whose fovea was involved with branch retinal vein occlusion within a month after noticing their symptoms. The best-corrected visual acuity, and vertical and horizontal metamorphopsia scores were obtained within one month, and at 3 months and 6 months after the onset of symptoms regardless of therapy. The metamorphopsia scores were measured with M-CHARTS. RESULTS: Although the average best-corrected visual acuity at 6 months was significantly better than that within a month of noticing symptoms, the average metamorphopsia scores did not improve after 6 months, and were not related to the average best-corrected visual acuity in either vertical or horizontal lines. CONCLUSIONS: The degree of metamorphopsia measured with M-CHARTS is an important parameter in addition to the best-corrected visual acuity for evaluating visual function in patients with branch retinal vein occlusion.

[Transient increased retinal hemorrhage and the retinal venous blood flow change in the course of non-ischemic central retinal vein occlusion treated with an anticoagulant].

PURPOSE: To investigate transient increased retinal hemorrhage during anticoagulant therapy and changes in the retinal venous blood flow in the course of non-ischemic central retinal vein occlusion (CRVO). METHODS: Seventeen patients(eighteen eyes) with non-ischemic CRVO were studied. The retinal vein diameter, blood velocity, and blood flow were determined by the laser Doppler method in seven patients. RESULTS: The retinal hemorrhage increased in nine eyes (50%); however, the retinal hemorrhage was transient and it finally decreased without vision loss in seven of the eyes. The retinal hemorrhage increased in the other two eyes and they became ischemic. The vessel diameter decreased and both velocity and blood flow increased in six of the seven patients two weeks after the treatment. There was no significant change in blood flow in cases which showed a transient increase in retinal hemorrhage, and they did not show a decrease in vision; however, only one eye which became ischemic showed a decrease in blood flow. CONCLUSION: We can judge whether an increase in retinal hemorrhage is transient or the clinical condition is getting worse in an early stage by measuring the retinal vein blood flow quantitatively by laser Doppler flowmetry.

Relationship between macular microcirculation and progression of diabetic macular edema.

PURPOSE: To investigate the relationship between blood flow velocity in perifoveal capillaries and retinal thickness at the central fovea in diabetic patients with clinically significant macular edema to elucidate the pathogenesis of diabetic macular edema. DESIGN: Comparative, cross-sectional, prospective study. PARTICIPANTS: Participants included diabetic patients with clinically significant macular edema (n = 22), matched diabetic patients without clinically significant macular edema (n = 22), and healthy volunteers (n = 16). METHODS: Perifoveal capillary blood flow velocity was measured with fluorescein angiography using a scanning laser ophthalmoscope and was analyzed by the tracing method. The severity of perifoveal capillary abnormalities among diabetic patients without clinically significant macular edema was classified by the size and outline of the foveal avascular zone and extent of foveal capillary loss at the baseline by the use of fluorescein angiograms. Retinal thickness at the central fovea was measured by optical coherence tomography. MAIN OUTCOME MEASURES: Relationship between perifoveal capillary blood flow velocity and retinal thickness at the central fovea. RESULTS: Perifoveal capillary blood flow velocity was significantly slower in the patients with clinically significant macular edema (0.94+/-0.09 mm/second) compared with the patients without clinically significant macular edema (1.22+/-0.20 mm/second) and the healthy volunteers (1.49+/-0.11 mm/second; P<0.0001). Capillary blood flow velocity negatively correlated with retinal thickness at the central fovea (r = -0.4018, P<0.0001). Capillary blood flow velocity varied among diabetic patients without clinically significant macular edema, and there were significant negative correlations between capillary blood flow velocity and the size of the foveal avascular zone (r = -0.52, P = 0.01), the outline of the foveal avascular zone (r = -0.44, P = 0.04), and the extent of foveal capillary loss (r = -0.51, P = 0.01). CONCLUSIONS: The reduction of perifoveal capillary blood flow velocity may occur before the increase of retinal thickness at the central fovea in the diabetic patients. It is possible that long-term reduction of blood flow velocity increases retinal thickness of the macula and may play an important role in the development and the progression of diabetic macular edema.

Tracing method in the assessment of retinal capillary blood flow velocity by fluorescein angiography with scanning laser ophthalmoscope.

PURPOSE: To evaluate the feasibility of a new method (the tracing method) for measuring perifoveal capillary blood flow velocity (BFV). METHODS: The BFV in the perifoveal capillaries was measured in 12 eyes of healthy subjects and 12 eyes of patients with clinically significant macular edema (CSME) by fluorescein angiography using a scanning laser ophthalmoscope by either the tracing method or the conventional method. A randomized crossover design was employed to assign the subjects to each method. RESULTS: The number of capillaries recognized by the tracing method in healthy subjects and in patients with CSME was significantly higher than that recognized with the conventional method (P = 0.0134 and P = 0.0108, respectively). The number of fluorescent dots detected by the tracing method in healthy subjects and in patients with CSME was also significantly higher than that detected with the conventional method (P = 0.0002 and P = 0.0137, respectively). Accurate detection of the movement of fluorescent dots and analysis of BFV were possible with the tracing method. The BFV varied within each perifoveal capillary, and the mean BFV also varied according to capillary location in the macula. CONCLUSION: The new tracing method is useful for analyzing the retinal capillary BFV in healthy subjects and in patients with CSME.

Modified technique to create retinal detachment during macular translocation surgery.

PURPOSE: To report a modified technique for creating total retinal detachment during macular translocation surgery with a 360-degree retinotomy. DESIGN: Interventional case series. METHODS: After vitrectomy, BSS Plus (Alcon, Fort Worth, TX, USA) was injected into the subretinal space with a 39-gauge needle to create a small retinal detachment. The tip of a 20-gauge silicone-tipped needle was then placed in the hole created by the needle, and BSS Plus was injected subretinally at a high flow rate. RESULTS: In 10 eyes (10 patients), we created one iatrogenic retinal hole in seven eyes and two holes in three eyes. The time needed to create total retinal detachment was decreased. CONCLUSIONS: Our technique seems to make creation of a total retinal detachment easier compared with the previous standard procedure and may reduce postoperative complications following macular translocation surgery with a 360-degree retinotomy.