Cataract surgery induces retinal pro-inflammatory gene expression and protein secretion

To investigate the effect(s) of cataract surgery on the expression of pro-inflammatory genes and proteins in the retina using an experimental rodent model. An extracapsular lens extraction was performed in one eye of C57BL/6 mice (n=24); the contralateral unoperated eyes (n =24) as well as eyes from unoperated animals (n = 9) served as controls. The neurosensory retina and retinal pigment epithelium (RPE)/choroid were collected postoperatively. Expression of genes involved in the acute inflammatory/ injury response, including IL-1ß, fibroblast growth factor, transforming growth factor ß, chemokine CCL2, SDF-1, and complements C3, C4, and factor B (CFB), were examined by real-time PCR and, selectively, by immunohistochemistry. The expression of IL-1 ß and CCL2 genes was markedly upregulated (>0-fold, P >0.01) in the neurosensory retina 30 minutes postoperatively and maintained for the 2-week postoperative period of observation; IL-1 ß expression was also upregulated in RPE/choroid. The expression of complement C3 (>-fold) and CFB (>0-fold) genes in the neurosensory retina was also significantly upregulated (P

Paraquat-Induced Retinal Degeneration Is Exaggerated in CX3CR1-Deficient Mice and Is Associated with Increased Retinal Inflammation

PURPOSE:
To investigate the role of the Fractalkine receptor CX3CR1 pathway in oxidative insults-mediated retinal degeneration and immune activation.
METHODS:
A prooxidant, paraquat (0.75 µM) was injected into the vitreous of C57BL/6J, CX3CR1(gpf/+), and CX3CR1(gfp/gfp) mice. Retinal lesions were investigated clinically by topic endoscopic fundus imaging and fluorescence angiography, and pathologically by light- and electron microscopy. Retinal immune gene expression was determined by real-time RT-PCR. Microglial activation and immune cell infiltration were examined by confocal microscopy of retinal flatmounts.
RESULTS:
Intravitreal injection of paraquat (0.75 µM) resulted in acute retinal capillary nonperfusion within 2 days, which improved from 4 days to 4 weeks postinjection (p.i.). Panretinal degeneration was observed at 4 days p.i. and progressed further at 4 weeks p.i. In the absence of CX3CR1, retinal degeneration was exaggerated and was accompanied by increased TNF-a, iNOS, IL-1ß, Ccl2, and Casp-1 gene expression. Confocal microscopy of retinal flatmounts revealed microglial activation and CD44(+)MHC-II(+) monocyte and GR1(+) neutrophil infiltration in paraquat-injected eyes. The number of activated microglia and infiltrating leukocytes was significantly higher in CX3CR1(gfp/gfp) mice than in CX3CR1(gfp/+) mice.
CONCLUSIONS:
Our results suggest that the CX3CR1 signaling pathway may play an important role in controlling retinal inflammation under oxidative and ischemia/reperfusion conditions. In the absence of CX3CR1, uncontrolled retinal inflammation results in exaggerated retinal degeneration.

Screening tests for detecting open-angle glaucoma: systematic review and meta-analysis

PURPOSE: To assess the comparative accuracy of potential screening tests for open angle glaucoma (OAG).

METHODS: Medline, Embase, Biosis (to November 2005), Science Citation Index (to December 2005), and The Cochrane Library (Issue 4, 2005) were searched. Studies assessing candidate screening tests for detecting OAG in persons older than 40 years that reported true and false positives and negatives were included. Meta-analysis was undertaken using the hierarchical summary receiver operating characteristic model.

RESULTS: Forty studies enrolling over 48,000 people reported nine tests. Most tests were reported by only a few studies. Frequency-doubling technology (FDT; C-20-1) was significantly more sensitive than ophthalmoscopy (30, 95% credible interval [CrI] 0-62) and Goldmann applanation tonometry (GAT; 45, 95% CrI 17-68), whereas threshold standard automated perimetry (SAP) and Heidelberg Retinal Tomograph (HRT II) were both more sensitive than GAT (41, 95% CrI 14-64 and 39, 95% CrI 3-64, respectively). GAT was more specific than both FDT C-20-5 (19, 95% CrI 0-53) and threshold SAP (14, 95% CrI 1-37). Judging performance by diagnostic odds ratio, FDT, oculokinetic perimetry, and HRT II are promising tests. Ophthalmoscopy, SAP, retinal photography, and GAT had relatively poor performance as single tests. These findings are based on heterogeneous data of limited quality and as such are associated with considerable uncertainty.

CONCLUSIONS: No test or group of tests was clearly superior for glaucoma screening. Further research is needed to evaluate the comparative accuracy of the most promising tests.

Evaluation of quality of life and priorities of patients with glaucoma

PURPOSE: To investigate the quality of life and priorities of patients with glaucoma.

METHODS: Patients diagnosed with glaucoma and no other ocular comorbidity were consecutively recruited. Clinical information was collected. Participants were asked to complete three questionnaires: EuroQuol (EQ-5D), time tradeoff (TTO), and choice-based conjoint analysis. The latter used five-attribute outcomes: (1) reading and seeing detail, (2) peripheral vision, (3) darkness and glare, (4) household chores, and (5) outdoor mobility. Visual field loss was estimated by using binocular integrated visual fields (IVFs).

RESULTS: Of 84 patients invited to participate, 72 were enrolled in the study. The conjoint utilities showed that the two main priorities were "reading and seeing detail" and "outdoor mobility." This rank order was stable across all segmentations of the data by demographic or visual state. However, the relative emphasis of these priorities changed with increasing visual field loss, with concerns for central vision increasing, whereas those for outdoor mobility decreased. Two subgroups of patients with differing priorities on the two main attributes were identified. Only 17% of patients (those with poorer visual acuity) were prepared to consider TTO. A principal component analysis revealed relatively independent components (i.e., low correlations) between the three different methodologies for assessing quality of life.

CONCLUSIONS: Assessments of quality of life using different methodologies have been shown to produce different outcomes with low intercorrelations between them. Only a minority of patients were prepared to trade time for a return to normal vision. Conjoint analysis showed two subgroups with different priorities. Severity of glaucoma influenced the relative importance of priorities.