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Ophthalmic research [journal]
- Ocular Toxoplasmosis: Recent Aspects of Pathophysiology and Clinical Implications. [JOURNAL ARTICLE]
- Ophthalmic Res 2014 Sep 19; 52(3):116-123.
Toxoplasma gondii is an extremely successful opportunistic parasite which infects approximately one third of the human population worldwide. The impact of this parasite on human health becomes particularly manifest in congenital damage with infection and subsequent inflammation of neuronal tissues including the retina. Although advances in our understanding could be achieved in ocular toxoplasmosis, large gaps still exist on factors influencing the epidemiology and pathophysiology of this potentially blinding disease. We are only at the beginning of understanding the complex biology of this parasite and its mechanisms of invasion, virulence and interaction with the host's immune response. Since it is a preventable cause of blindness, it is necessary to assess factors that have the potential to control this disease in the future. This mini review will focus on recent advances in postnatal acquired ocular infection and the factors that may influence its prevalence and functional outcome. © 2014 S. Karger AG, Basel.
- Treatment of Dry Age-Related Macular Degeneration. [JOURNAL ARTICLE]
- Ophthalmic Res 2014 Sep 11; 52(3):107-115.
A number of different approaches are under development for treating nonexudative manifestations of age-related macular degeneration (AMD). Some interventions target specific pathways that are believed to play a role in AMD pathogenesis, e.g. oxidative damage, lipofuscin accumulation, chronic inflammation (including complement activation), extracellular matrix changes (e.g. β-amyloid accumulation), impaired choroidal blood flow, and apoptosis. In principle, these therapies can be combined ('combination therapy'), which may lead to synergistic effects that include better visual outcome, less likelihood for 'escape' (i.e. drug resistance), and less frequent treatment. © 2014 S. Karger AG, Basel.
- rs4711751 and rs1999930 Are Not Associated with Neovascular Age-Related Macular Degeneration or Polypoidal Choroidal Vasculopathy in the Chinese Population. [Journal Article]
- Ophthalmic Res 2014; 52(2):102-6.
rs1999930 and rs4711751 have recently been identified as novel variants associated with advanced age-related macular degeneration (AMD) in populations of European ancestry. We aimed to investigate whether these two single nucleotide polymorphisms (SNPs) were associated with neovascular AMD (nAMD) or with polypoidal choroidal vasculopathy (PCV), a variant of AMD in Asians, using a Chinese case-control study.A total of 900 subjects, including 300 controls, 300 cases with nAMD and 300 cases with PCV, were included in the present study. Genomic DNA was extracted from venous blood leukocytes. The allelic variants of rs1999930 and rs4711751 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The differences in allele distribution between cases and controls were tested by a χ(2) test, with additional adjustments for age and gender using logistic regression. The statistical power was also calculated. Values of p < 0.05 were considered statistically significant.No statistically significant association was observed between the two polymorphisms of nAMD or PCV phenotype (p > 0.05 for all comparisons). The difference remained insignificant after correction for age and gender (p > 0.05 for all comparisons). The statistical powers to detect the association between these two SNPs and nAMD or PCV range from 0.05 to 0.36, assuming conventional levels of statistical significance.In the present study, we could not replicate the reported association of these two SNPs and either nAMD or PCV in a Chinese population, suggesting that they are unlikely to be a major AMD and PCV susceptibility gene locus in the Chinese population. Considering the low power value, a large sample size is required to draw more reliable conclusions. © 2014 S. Karger AG, Basel.
- Influence of macular choroidal thickness on visual function in highly myopic eyes. [Journal Article]
- Ophthalmic Res 2014; 52(2):97-101.
To explore the retinal and choroidal thicknesses (RT, CT), as measured using enhanced depth imaging (EDI) optical coherence tomography (OCT, Spectralis) in highly myopic eyes and its relationship with visual function.Prospective, case-control, noninterventional clinical study. CT was measured by EDI-OCT in highly myopic eyes (≥6 dpt) without any macular diseases and age-matched control eyes. A complete ophthalmological examination, visual acuity assessment and MP1 microperimetry were obtained.38 myopic (15 M/23 F, mean age 51 ± 8.9 years) and 21 control eyes (5 M/16 F, mean age 50 ± 5.4 years) were included. The myopic mean refractive error was -13.3 ± 4.9 dpt and axial length 29.2 ± 2.2 mm. The mean best-corrected visual acuity (BCVA) was lower in highly myopic than in control eyes (77.3 ± 9.25 vs. 84.8 ± 0.6 letters, p = 0.0001, respectively) as was the mean retinal sensitivity (MRS; 16.32 ± 2.6 vs. 19.9 ± 0.2 dB, p < 0.0001). While RT was similar between groups (291.5 ± 24.2 vs. 283.6 ± 13.9 µm, p = 0.06, respectively), subfoveal CT was thinner in highly myopic compared to control eyes (114.3 ± 78.5 vs. 272.6 ± 110.2 µm, p < 0.0001). A significant relationship was found between subfoveal CT and MRS (R(2) = 0.22; p = 0.003) and BCVA (R(2) = 0.13; p = 0.027).Macular function is reduced in highly myopic eyes without any visible macular diseases compared to controls, and a significant proportion of the macular function variability seems to be related to a reduced CT. © 2014 S. Karger AG, Basel.
- Update of Intravitreal Steroids for the Treatment of Diabetic Macular Edema. [JOURNAL ARTICLE]
- Ophthalmic Res 2014 Aug 29; 52(2):89-96.
Diabetic macular edema is considered the most important factor related to visual impairment in patients with diabetic retinopathy. Together with the use of grid and focal laser photocoagulation, today the intravitreal administration of pharmacotherapies represents the standard of care for the treatment of this complication: anti-vascular endothelium growth factor agents and steroids are the drugs currently used for this aim. Differently from laser therapy, which prevents visual deterioration, the intravitreal approach allows the promotion of visual recovery. However, the intravitreal injections require to be repeated with high frequency, and this carries the risk of drug- and procedure-related adverse effects. © 2014 S. Karger AG, Basel.
- Thrombospondin-1 is produced by retinal glial cells and inhibits the growth of vascular endothelial cells. [Journal Article]
- Ophthalmic Res 2014; 52(2):81-8.
By the release of antiangiogenic factors, Müller glial cells provide an angiostatic environment in the normal and ischemic retina. We determined whether Müller cells produce thrombospondin-1 (TSP-1), a known inhibitor of angiogenesis.Secretion of TSP-1 by cultured Müller cells was determined with ELISA. Slices of rat retinas and surgically excised retinal membranes of human subjects were immunostained against TSP-1 and the glial marker vimentin. The effects of TSP-1 on the growth of bovine retinal endothelial cells (BRECs) and activation of ERK1/2 were determined with DNA synthesis and migration assays, and Western blotting, respectively.Cultured Müller cells secrete TSP-1 under normoxic and hypoxic (0.2% O2) conditions. Secretion of TSP-1 was increased in hypoxia compared to normoxia. In rat retinal slices, glial, retinal ganglion, and possibly horizontal cells were stained for TSP-1. Retinal glial cells in preretinal membranes from human subjects with nonhypoxic epiretinal gliosis (macular pucker) and proliferative diabetic retinopathy, respectively, were immunopositive for TSP-1. Exogenous TSP-1 reduced the VEGF-induced proliferation and migration of BRECs and decreased the phosphorylation level of ERK1/2 in BRECs.The data suggest that Müller cells are one major source of TSP-1 in the normal and ischemic retina. Glia-derived TSP1 may inhibit angiogenic responses in the ischemic retina. © 2014 S. Karger AG, Basel.
- Intravitreal functional plasminogen in eyes with branch retinal vein occlusion. [Journal Article]
- Ophthalmic Res 2014; 52(2):74-80.
To evaluate whether intravitreal functional plasminogen is elevated in eyes with branch retinal vein occlusion (BRVO) and to discover whether intravitreal plasminogen activities are correlated with the extent of blood-retina barrier (BRB) breakdown.Our study is a prospective case series of 20 consecutive patients with BRVO and 10 consecutive patients serving as controls. Vitreous taps were extracted from the central vitreous body and plasminogen was functionally determined in an innovative, ultrasensitive p-nitroanilide reaction after activation with streptokinase (100% of normal, %N = functional plasminogen in pooled normal citrated plasma). Intravitreal VEGF levels were assayed to estimate BRB breakdown.Intravitreal functional plasminogen was detected in all analyzed samples (n = 30) and mean (±SD) plasminogen activities were found to be 0.97 ± 1.06%N (range: 0.03-3.9%N). Patients suffering from BRVO exhibited significantly higher intravitreal plasminogen (1.35 ± 1.11%N) in comparison with controls (0.20 ± 0.21%N, p < 0.001). Intravitreal VEGF concentrations in the BRVO group (576 ± 547 pg/ml) were significantly higher than these in controls (111 ± 120 pg/ml, p = 0.003). There was a significant correlation between intravitreal functional plasminogen and intravitreal VEGF levels (r = 0.519, p = 0.003).Intravitreal functional plasminogen is significantly elevated in eyes suffering from BRVO and correlates with the extent of BRB breakdown. The induction of posterior vitreous detachment by using intravitreally administered recombinant tissue plasminogen activator (enzymatic vitreolysis) should be explored in further investigations. © 2014 S. Karger AG, Basel.
- Detection of Fovea-Threatening Diabetic Macular Edema by Optical Coherence Tomography to Maintain Good Vision by Prophylactic Treatment. [JOURNAL ARTICLE]
- Ophthalmic Res 2014 Jul 18; 52(2):65-73.
Background/Aims: To establish a screening and treatment method for fovea-threatening diabetic macular edema (DME) using spectral-domain optical coherence tomography (SD-OCT). In order to maintain good visual acuity (VA), focal/grid laser treatment for screened fovea-threatening DME was evaluated based on macular thickness map images produced by SD-OCT. Methods: In 66 diabetic eyes with no visual deterioration, the sensitivity and the specificity of SD-OCT without the use of mydriatics for the detection of fovea-threatening DME were determined. A definite diagnosis of DME was made under mydriasis, using slitlamp biomicroscopy with a contact lens. Eyes with fovea-threatening DME then underwent prophylactic focal/grid laser treatment. The main outcome measures were corrected VA and central macular thickness (CMT). Results: A definitive diagnosis of DME was made in 5 of the 66 eyes, while macular thickening above the 99th percentile was detected in 11 (Cirrus®) or 13 (RS-3000®) eyes by SD-OCT. The focal/grid laser treatment of the 5 eyes with fovea-threatening DME successfully maintained good VA, which was 0.91 ± 0.76 (average: 20/22; 0.04 ± 0.12 logMAR) before treatment and 0.89 ± 0.70 (average: 20/22; 0.05 ± 0.15 logMAR; p = 0.88) 1 year afterwards. The average CMT was stable before and after focal/grid lasering at 302 ± 29 and 329 ± 55 µm, respectively (p = 0.99). Conclusions: The detection of fovea-threatening DME is feasible by SD-OCT without using mydriatics. Prophylactic treatment, such as with focal/grid lasers, was effective in maintaining good VA by avoiding an otherwise highly likely foveal involvement. © 2014 S. Karger AG, Basel.
- Host-Derived Endothelial Regeneration of Corneal Transplants in a Rat Keratoplasty Model. [JOURNAL ARTICLE]
- Ophthalmic Res 2014 Jul 1; 52(2):60-64.
Background: It has been observed that formerly rejected opaque corneal transplants can regain clarity in the rat. We hypothesized that graft endothelium is regenerated by the host. Therefore, we used green fluorescent protein (GFP) transgenic rats to assess the origin of cells following keratoplasty. Methods: Allogeneic corneal transplantations were carried out between Fischer strain rats as graft donors and GFP-transgenic Lewis rats as recipients. In a second group, syngeneic transplantations were performed between GFP-negative Lewis donors and GFP-positive Lewis recipients, where endothelial-cell-free grafts after mechanical endothelial debridement were used. All grafts were followed up clinically for signs of opacity and rejection. After 6 weeks, corneal flatmounts counterstained with DAPI were analyzed by confocal microscopy. Results: Syngeneic transplantation of endothelial-cell-free grafts led to medium opacity levels without rejection and to subsequent clearing. All grafts showed a population of GFP-positive, host-derived endothelial cells on the graft after 6 weeks. In the allogeneic transplantation group, all grafts but one were rejected after a median of 17 days. While the graft that was not rejected maintained the GFP-negative transplant endothelium, all formerly rejected grafts showed GFP-positive endothelium on the transplant after 6 weeks, accompanied by clinical clearing of the graft. Conclusion: GPF positivity shows that in both a syngeneic and an allogeneic setting, the host-derived corneal endothelium can compensate for the endothelial cell loss of the graft. Following rejection, the grafts are repopulated by host-derived endothelial cells in the rat. This finding demonstrates a high regenerative capacity of the peripheral corneal endothelium in the rat, which should be considered whenever interpreting rat keratoplasty results. © 2014 S. Karger AG, Basel.
- Geographic Atrophy Progression in Eyes with Age-Related Macular Degeneration: Role of Fundus Autofluorescence Patterns, Fellow Eye and Baseline Atrophy Area. [JOURNAL ARTICLE]
- Ophthalmic Res 2014 Jun 27; 52(2):53-59.
Background/Objective: To evaluate if fundus autofluorescence (FAF) patterns around geographic atrophy (GA) and the status of the fellow eye have an impact on GA progression. Methods: We included 54 eyes of 35 patients with GA. Areas of GA were quantified by RegionFinder software. Results: GA progression rates in eyes with a diffuse trickling pattern (median 1.42 mm(2)/year) were significantly higher than in normal eyes (median 0.22 mm(2)/year) and eyes with other diffuse FAF patterns (median 0.46 mm(2)/year). Eyes with a banded pattern had a significantly higher progression rate (median 0.81 mm(2)/year) than those without any FAF abnormalities (p = 0.038). The group with baseline total atrophy of the eyes <1 disk area (DA; median 0.42 mm(2)) had an inverse relation with GA progression compared to the groups with baseline atrophy >1 DA (p < 0.05). Conclusion: Diffuse trickling and banded patterns may have an impact on GA progression and may serve as prognostic factors. © 2014 S. Karger AG, Basel.