Purpose: The purpose of this study is to compare the aqueous humor level of Silent Information Regulator T1 (SIRT1) between patients with Age-related Macular Degeneration (AMD) and cataract patients. Materials and Methods: Aqueous humor level of SIRT1 was measured by enzyme-linked immunosorbent assay in 13 patients with wet-type AMD (n=13, AMD group) and 13 patients with cataracts (cataract group). In addition, the thickness of each retinal layer was determined by optical coherence tomography. Results: The aqueous humor level of SIRT1 was significantly lower in the AMD group than in the cataract group (p=0.007). In the AMD group, the SIRT1 level was positively correlated with the thickness of the retinal ganglion cell layer (r=0.31) and the inner nuclear layer (r=0.76). Conclusion: The aqueous level of SIRT1 decreased as the ganglion cell layer and inner nuclear layer became thinner, suggesting that reduction of SIRT1 activity might be involved in the pathogenesis of this disease.

Purpose: To compare aqueous humor levels of various cytokines between patients with age-related macular degeneration (AMD) and cataract patients. Methods: Thirteen eyes with wet-type AMD (AMD group) and 14 eyes with cataract (cataract group) were studied. Aqueous humor levels of 11 factors (vascular endothelial growth factor receptors, growth factors, and inflammatory factors) were measured by the suspension array method. Results: Aqueous humor levels of vascular endothelial growth factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, sVEGFR-2, and inflammatory factors (monocyte chemotactic protein (MCP)-1, interleukin (IL)-6, and IL-8) were significantly higher in the AMD group than in the cataract group (all p < 0.05). In contrast, aqueous humor levels of placental growth factor (PGF), tumor necrosis factor-α, soluble intercellular adhesion molecule (sICAM)-1, IL-12 (p70), and IL-13 showed no significant difference between the two groups. There were significant correlations between sVEGFR-1 or sVEGFR-2 levels and some of the inflammatory molecules (PGF, sICAM-1, MCP-1, IL-6, and IL-8). Conclusions: These findings suggest that various cytokines/growth factors involved in inflammation and angiogenesis may be associated with the pathogenesis of AMD.

Purpose: Retinal adenosine triphosphate is mainly produced via glycolysis, so inhibition of glycolysis may promote the onset and progression of age-related macular degeneration (AMD). When glycolysis is inhibited, pyruvate is metabolized by lactic acid fermentation instead of entering the mitochondrial tricarboxylic acid (TCA) cycle. We measured urinary pyruvate and lactate levels in patients with AMD. Methods: Eight patients with typical AMD (tAMD group) and 9 patients with polypoidal choroidal vasculopathy (PCV group) were enrolled. Urinary levels of pyruvate, lactate, α-hydroxybutyrate, and β-hydroxybutyrate were measured in all patients. Results: The mean urinary levels of pyruvate and lactate were 8.0 ± 2.8 and 7.5 ± 8.3 μg/mg creatinine (reference values: 0.5-6.6 and 0.0-1.6), respectively, with the mean increase over the reference value being 83.6 ± 51.1% and 426.5 ± 527.8%, respectively. In 12 patients (70.6%), the lactate/pyruvate ratio was above the reference range. Urinary levels of α-hydroxybutyrate and β-hydroxybutyrate were decreased by -31.9 ± 15.2% and -33.1 ± 17.5% compared with the mean reference values. There were no significant differences of any of these glycolysis metabolites between the tAMD and PCV groups. Multivariate analysis revealed that none of the variables tested, including patient background factors (age, hypertension, diabetes, hyperlipidemia, cerebrovascular disease, alcohol, smoking, visual acuity, and AMD phenotype), were significantly associated with the lactate/pyruvate ratio. Conclusion: A high lactate/pyruvate ratio is a well-known marker of mitochondrial impairment, and it indicates poor oxidative function in AMD. Our results suggest that increased lactate levels may be implicated in the pathogenesis of AMD.

In this paper, we review current knowledge about the retinal neuroprotective effect of sirtuins. The sirtuins are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases that are involved in mammalian diseases of aging. The human genome encodes seven different sirtuins (SIRT1-7). SIRT1 is localized in the nucleus and cytoplasm of the cells making up all normal ocular structures, including the retina. Age-related macular degeneration (AMD) is a typical age-related condition due to the lifelong accumulation of molecular damage caused by reactive oxygen species (ROS). SIRT1 can decrease ROS levels and promotes cell survival under oxidative stress. Upregulation of SIRT1 has a protective effect against retinal degeneration in animal models. Resveratrol is a polyphenolic SIRT1 activator that has been shown to increase the lifespan and to protect various organs against aging, including oxidative stress-induced retinal damage. Anti-aging therapy with resveratrol could be an attractive treatment option for age-related macular degeneration.

BACKGROUND AND OBJECTIVETo evaluate the influence of serous retinal detachment (SRD) on the outcome of pars plana vitrectomy (PPV) for macular edema in patients with branch retinal vein occlusion (BRVO).PATIENTS AND METHODSIn an interventional case series, 20 patients (20 eyes) with BRVO and macular edema underwent PPV, including 12 patients with SRD and eight with cystoid macular edema (CME). Microperimetry of the macular region and optical coherence tomography were performed before and 6 months after PPV.RESULTSIn both the CME and SRD groups, the mean macular thickness and macular volume decreased significantly from baseline to 3 and 6 months after PPV (all P < .01), while visual acuity improved significantly in both groups (both P < .01). However, mean macular sensitivity only increased significantly in the SRD group (P < .05).CONCLUSIONPPV achieves greater improvement of macular sensitivity in BRVO patients with SRD than in those with CME.

The sirtuins are a highly conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases that helps regulate the lifespan of diverse organisms. The human genome encodes seven different sirtuins (SIRT1-7), which share a common catalytic core domain but possess distinct N- and C-terminal extensions. Dysfunction of some sirtuins have been associated with age-related diseases, such as cancer, type II diabetes, obesity-associated metabolic diseases, neurodegeneration, and cardiac aging, as well as the response to environmental stress. SIRT1 is one of the targets of resveratrol, a polyphenolic SIRT1 activator that has been shown to increase the lifespan and to protect various organs against aging. A number of animal studies have been conducted to examine the role of sirtuins in ocular aging. Here we review current knowledge about SIRT1 and ocular aging. The available data indicate that SIRT1 is localized in the nucleus and cytoplasm of cells forming all normal ocular structures, including the cornea, lens, iris, ciliary body, and retina. Upregulation of SIRT1 has been shown to have an important protective effect against various ocular diseases, such as cataract, retinal degeneration, optic neuritis, and uveitis, in animal models. These results suggest that SIRT1 may provide protection against diseases related to oxidative stress-induced ocular damage, including cataract, age-related macular degeneration, and optic nerve degeneration in glaucoma patients.

Central retinal vein occlusion (CRVO) is a common retinal vascular disease that often results in macular oedema, which is the most frequent cause of visual impairment in these patients [1]. Therefore, it is important to understand the vascular and haemodynamic abnormalities that underlie the progression of macular oedema in CRVO. Remky et al. [2] found that the perifoveal blood flow velocity (BFV) was significantly reduced in CRVO patients compared with healthy subjects by using scanning laser ophthalmoscopy with fluorescein angiography (FA) to measure BFV in the perifoveal capillaries based on the movement of fluorescent dots. However, the relationship between perifoveal BFV and macular oedema in CRVO patients remains unclear. Accordingly, we investigated the relation between perifoveal capillary BFV and retinal thickness at the central fovea in CRVO patients with macular oedema, healthy volunteers, and patients who had branch retinal vein occlusion (BRVO) with macular oedema [3].

Purpose: To investigate whether vascular endothelial growth factor, soluble intercellular adhesion molecule-1 (sICAM-1), and pigment epithelium-derived factor are associated with serous retinal detachment (SRD) secondary to branch retinal vein occlusion.Methods: The subjects were 44 branch retinal vein occlusion patients with macular edema and 16 controls. Patients were divided into 2 groups by optical coherence tomography findings, that is, 18 patients with SRD and 26 with cystoid macular edema. The area of capillary nonperfusion was measured with fluorescein angiography and Scion Image software. Vitreous fluid samples obtained during pars plana vitrectomy were examined by enzyme-linked immunosorbent assay.Results: The incidence of major branch retinal vein occlusion was significantly higher in SRD patients (17/18, 94%) than in cystoid macular edema patients (15/26, 58%, P = 0.007), while the nonperfused retinal area was significantly larger in SRD patients (P = 0.006). Vitreous fluid levels of vascular endothelial growth factor and soluble intercellular adhesion molecule-1 (sICAM-1) showed a significant increase across the 3 groups (control group, cystoid macular edema group, and SRD group) (P-trend, 0.001 and P-trend, 0.001, respectively), while the pigment epithelium-derived factor level showed a significant decrease across the 3 groups (P-trend, 0.001).Conclusion: An excessive increase of vascular permeability secondary to upregulation of vascular endothelial growth factor and soluble intercellular adhesion molecule-1 (sICAM-1) along with downregulation of pigment epithelium-derived factor may contribute to the development of SRD in BRVO patients. RETINA 32:86-91, 2012

Purpose: To evaluate functional and morphological changes of the macula after intravitreal injection of triamcinolone acetonide (IVTA) for macular edema with branch retinal vein occlusion (BRVO). Methods: Twenty patients with BRVO (mean age: 69.7±9.8 years; 14 women and 6 men) received IVTA. Macular function was documented by microperimetry and best-corrected visual acuity (BCVA) was determined. Retinal thickness and retinal volume were measured by optical coherence tomography, and mean retinal sensitivity was calculated for each of 9 macular subfields. Results: Mean BCVA significantly improved 6 months after IVTA. Mean retinal sensitivity, retinal thickness, and retinal volume significantly improved after 6 months in 4, 8, and 8 subfields, respectively. On multivariate analysis, improvement of retinal sensitivity was significantly correlated with the percent changes of both retinal thickness and retinal volume in 2 subfields [superior inner (the occlusion site) and temporal outer], although improvement of visual acuity was not significantly correlated with the percent change of macular edema in any of the 9 subfields. Conclusions: These findings suggest that IVTA can improve both functional and morphological changes due to macular edema in BRVO patients, and that morphological improvement after IVTA might be useful for assessing the functional prognosis of BRVO with macular edema.

Vitreous surgery has improved remarkably with various advances in surgical instruments and techniques. The two most important breakthrough in recent years have been the introduction of small-gauge pars plana vitrectomy (PPV) systems and new illumination devices. Compared with traditional 20-gauge PPV, sutureless small-gauge PPV appears to be safer, with a shorter operating time, less postoperative inflammation, less patient discomfort, and more rapid recovery of visual acuity. This article reviews recent progress in the surgical management of vitreous disease with a historical perspective.

Purpose: To investigate the effect of intravitreal triamcinolone acetonide (TA) on aqueous humor levels of vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule 1 (sICAM-1), and pigment epithelium-derived factor (PEDF) in patients with central retinal vein occlusion (CRVO) and macular edema. Methods: We measured VEGF, sICAM-1, and PEDF levels in aqueous humor samples from 2 eyes of 2 CRVO patients during injection of TA. Results: In both patients, the VEGF and sICAM-1 levels in aqueous humor samples obtained during initial injection of TA were higher than at the time of reinjection. Conversely, the initial PEDF levels were lower than those at reinjection. Conclusions: Aqueous humor levels of VEGF and sICAM-1 were decreased by TA treatment in 2 CRVO patients, while PEDF was increased. Intravitreal TA could be an option for CRVO patients with a low PEDF level and/or moderate VEGF and sICAM-1 levels.

Background: To evaluate the relationships among vitreous fluid levels of soluble vascular endothelial growth factor receptor-2 (sVEGFR-2), vascular endothelial growth factor (VEGF), and the severity of macular oedema secondary to branch retinal vein occlusion (BRVO). Methods: Twenty-five BRVO patients with macular oedema were enrolled. Vitreous fluid samples were obtained during vitreoretinal surgery to measure the levels of sVEGFR-2 and VEGF. Macular oedema was examined by optical coherence tomography. Results: The vitreous fluid levels of VEGF and sVEGFR-2 were significantly correlated with the severity of macular oedema (ρ = 0.54, p = 0.008 and ρ = 0.40, p = 0.047, respectively). The sVEGFR-2 × VEGF product was also significantly correlated with the severity of macular oedema (ρ = 0.62, p = 0.003). Conclusions: The severity of macular oedema was more closely associated with sVEGFR-2 × VEGF than sVEGFR-2 or VEGF alone, suggesting that macular oedema in BRVO patients may be influenced by both VEGF and sVEGFR-2.

To investigate the correlation between the perifoveal capillary blood flow velocity (BFV) and the vitreous level of pigment epithelium-derived factor (PEDF) in patients with branch retinal vein occlusion (BRVO) and macular edema. In a retrospective interventional study of patients with BRVO and macular edema, undiluted vitreous specimens were obtained from 12 eyes of 12 patients. The level of PEDF was then measured in vitreous samples by an enzyme-linked immunosorbent assay. Before vitreous fluid sampling, perifoveal capillary BFV was measured by fluorescein angiography with a scanning laser ophthalmoscope and the tracing method. Subsequently, the relationship between perifoveal capillary BFV and the vitreous level of PEDF was investigated. There was a significant positive correlation between BFV and the vitreous level of PEDF in the 12 patients (ρ = 0.75, p = 0.013). The vitreous level of PEDF may influence macular microcirculation in patients with BRVO and macular edema.

BACKGROUND/AIMS:Branch retinal vein occlusion (BRVO) leads to retinal ischaemia, which then induces upregulation of various inflammatory factors, including vascular endothelial growth factor (VEGF). The aim of this study was to determine whether there was a correlation between inflammatory factors and components of the electroretinogram (ERG) in patients with BRVO.METHODS:In 19 BRVO patients with macular oedema, vitreous fluid samples were obtained during vitreoretinal surgery to measure the levels of four inflammatory factors (VEGF, soluble intercellular adhesion molecule-1 (sICAM-1), interleukin (IL)-6 and monocyte chemotactic protein (MCP)-1). The amplitude and implicit time of the a-wave cone, b-wave cone and 30 Hz flicker were calculated automatically from the ERG. Correlations between the different components of the ERG and the four inflammatory factors were investigated.RESULTS:Vitreous fluid levels of two factors (IL-6 and MCP-1) were significantly correlated with the implicit time of the cone b-wave (p=0.035 and p=0.016, respectively). Vitreous fluid levels of all four factors (VEGF, sICAM-1, IL-6, and MCP-1) were significantly correlated with the implicit time of 30 Hz flicker (p=0.047, p=0.031, p=0.002 and p=0.009, respectively). Vitreous fluid levels of VEGF, sICAM-1, IL-6, and MCP-1 were significantly higher in patients with an implicit time ≥36 ms than with an implicit time <36 ms (p=0.042, p=0.048, p=0.003 and p=0.024, respectively).CONCLUSIONS:These findings suggest that the implicit times of the cone b-wave and 30 Hz flicker can be used to detect BRVO patients with macular oedema who have a high risk of ischaemia.

Concentrations of inflammatory factors were measured in 40 patients with macular edema due to major branch retinal vein occlusion (BRVO) or macular BRVO who were treated by pars plana vitrectomy. Vitreous fluid levels of vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule-1 (sICAM-1), and pigment epithelium-derived factor (PEDF) were determined. Visual acuity and central macular thickness were significantly improved at 6 months in both groups. Vitreous fluid levels of VEGF and sICAM-1 were higher in the major BRVO group than the macular BRVO group, while the PEDF level was lower in the major group than the macular group. The mean visual acuity and central macular thickness at 6 months were not significantly different between the macular and major groups. In conclusion, patients with major BRVO had higher vitreous levels of inflammatory factors and lower vitreous levels of anti-inflammatory PEDF. Accordingly, regulating inflammatory factors might be more important in major BRVO than macular BRVO.

PURPOSE:To evaluate the changes of macular sensitivity, thickness, and total macular volume after intravitreal injection of triamcinolone acetonide to treat macular edema with branch retinal vein occlusion. METHODS:Seventeen eyes of 17 patients with branch retinal vein occlusion with macular edema received intravitreal triamcinolone acetonide. Using capillary nonperfusion on fluorescein angiography, patients were classified into nonischemic or ischemic groups. Microperimetry was used to measure macular sensitivity within the central 4°, 10°, and 20° fields. Macular thickness and macular volume within these fields were measured by optical coherence tomography. RESULTS:The mean macular thickness within the central 4°, 10°, and 20° fields decreased significantly after intravitreal therapy (all Ps < 0.001) as did total macular volume (all Ps < 0.001). Visual acuity was significantly better at 3 and 6 months (P = 0.002) as was the mean macular sensitivity within the three fields (all Ps < 0.05). There were no significant differences in the trend profile of macular thickness and volume within the three fields between the ischemic and nonischemic groups. There were also no significant differences in the trend profile of visual acuity and macular sensitivity. CONCLUSION:Intravitreal triamcinolone acetonide may improve macular sensitivity and morphology in patients with ischemic and nonischemic branch retinal vein occlusion.