Retinal damage extends beyond the border of the detached retina in fovea-on retinal detachment

Purpose: The aim of this study was to investigate the preoperative and postoperative change in retinal sensitivity in relation to the distance to the retinal detachment (RD) in patients with fovea-on RD. Methods: We prospectively evaluated 13 patients with fovea-on RD and a healthy control eye. Preoperatively, OCT scans of the RD border and the macula were obtained. The RD border was highlighted on the SLO image. Microperimetry was used to assess the retinal sensitivity at the macula, the RD border and the retina around the RD border. At 6 weeks, 3 and 6 months postoperatively, follow-up examinations of OCT and microperimetry were performed in the study eye. Microperimetry was performed once in control eyes. Microperimetry data were overlaid on the SLO image. The shortest distance to the RD border was calculated for each sensitivity measurement. The change in retinal sensitivity was calculated as control-study. The relation between the change in retinal sensitivity and the distance to the RD border was assessed using a locally weighted scatterplot smoothing curve. Results: Preoperatively, the greatest loss in retinal sensitivity was 21 dB at 3° inside the RD which decreased linearly, through the RD border, and reached a plateau of 2 dB at 4°. For 6 weeks and 3 months postoperatively, the greatest retinal sensitivity loss remained at 3° inside the RD but was 4 dB and sensitivity loss decreased linearly to a plateau of 0 dB at 5° outside the RD. At 6 months postoperatively, the greatest sensitivity loss was 2 dB at 3° inside the RD, and decreased linearly to a plateau of 0 dB at 2° outside the RD. Conclusions: Retinal damage extends beyond the detached retina. Retinal sensitivity loss of the attached retina decreased drastically as the distance to the RD increased. Postoperative recovery occurred for both attached and detached retina.</p

Cyclic GMP in the pig vitreous and retina after experimental retinal detachment

Purpose: Earlier studies have revealed a decreased level of cGMP in vitreous fluid obtained from patients with a retinal detachment. To further investigate this phenomenon, we developed an experimental retinal detachment model in pigs. Methods: Experimental unilateral retinal detachments were induced in pig eyes by subretinal injection of 0.25% sodium hyaluronate. Fourteen days later the vitreous and retinas were analyzed for cGMP expression. Following enucleation, the retinas were incubated in the presence of a nonselective phosphodiesterase inhibitor (IBMX), and the particulate guanylyl cyclase stimulator atrial natriuretic peptide (ANP) or the soluble guanylyl cyclase stimulator sodium nitroprusside (SNP). cGMP was visualized in retinal wholemounts by immunochemistry combined with a computer based stereology system. cGMP levels in vitreous were determined by ELISA. Results: The mean vitreous cGMP level in pig eyes with a retinal detachment (1.45 pmol/ml) was significantly lower compared to the mean level of cGMP in healthy pig eyes (4.61 pmol/ml; p= 0.028 was considered significant). In the inner retina, ANP as well as SNP induced cGMP immunoreactivity in both detached and healthy retinas. After incubation with ANP, cGMP could also be detected in the outer nuclear layer of the detached retina, whereas this was not the case in the normal retina. Conclusions: Experimental retinal detachment in the pig eye leads to a decrease of cGMP levels in vitreous similar to that observed in clinical studies. This model may be helpful to analyze the mechanisms involved in cGMP dynamics following retinal detachment

Postoperative aqueous humour flare as a surrogate marker for proliferative vitreoretinopathy development

Purpose: As some surgical procedures have been shown to increase postoperative flare values and thus contribute to blood-ocular barrier breakdown, retinal reattachment surgery might influence the risk of developing proliferative vitreoretinopathy (PVR). Therefore, we investigated whether postoperative aqueous flare values are a surrogate marker for the development of postoperative PVR. Methods: We prospectively included 195 patients with primary rhegmatogenous retinal detachment (RRD) and measured aqueous laser flare preoperatively, and at 2 and 6 weeks postoperatively. Postoperative PVR was defined as reoperation for redetachment due to PVR membranes, within 6 months of initial surgery. Logistic regression and receiver operating characteristic (ROC) analysis determined whether higher postoperative flare values were associated with an increased risk of developing PVR later on. Results: Reoperation for postoperative PVR was needed in 12 (6.2%) patients; in 18 (9.2%), reoperation was not related to PVR. The median flare value for patients who would develop PVR was significantly higher than that of patients who would not develop PVR, both at 2 weeks (p = 0.001) and 6 weeks (p < 0.001) postoperatively. Logistic regression analyses showed that a higher flare value significantly increased the odds of developing PVR, either at 2 weeks [odds ratio (OR) 1.027; 95% CI: 1.010-1.044] or 6 weeks (OR 1.076; 95% CI: 1.038-1.115). Conclusion: Flare values both at 2 and 6 weeks postoperatively seem a good surrogate marker in terms of sensitivity and specificity for the development of postoperative PVR but have only a modest positive predictive value. The 2-week value would be more useful in terms of early recognition of high-risk patients and hence give the possibility to better study effects of treatment methods

Two autocrine pathways to regulate cyclic GMP synthesis in cultured human retinal pigment epithelial cells

AIM: To investigate the role of two separate enzymatic pathways [soluble (sGC) vs. particulate (pGC) guanylyl cyclase] in the synthesis of cyclic GMP (cGMP) in cultured human retinal pigment epithelial (RPE) cells. METHODS: cGMP accumulation was evaluated by quantitative analysis of cGMP immunoreactivity. RPE cells were also stained for inducible nitric oxide synthase (iNOS), ANP and beta(1)- and alpha(2)-subunits of sGC. RESULTS: We showed nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity and iNOS immunoreactivity in RPE cells. Incubation of the cells in the presence of 1 mM IBMX to inhibit phosphodiesterase activity, and the simultaneous inhibition of NOS activity with L-NAME suggested the involvement of sGC in maintaining a low level of cGMP in the RPE cells. The involvement of sGC was further supported by detection of the beta(1)- and alpha(2)-subunits of sGC. Incubation of the cells in the presence of atrial natriuretic peptide (ANP) to stimulate pGC strongly increased cGMP immunoreactivity. We also demonstrated the presence of ANP in all RPE cells. CONCLUSION: Cultured human RPE cells are capable of producing cGMP after stimulation of sGC or pGC. The presence of iNOS and ANP in all cells suggests two different autocrine pathways of stimulating cGMP production in these cells. The possible role of cGMP in the regulation iNOS gene expression and in the regulation of ANP is discussed

Cyclic GMP synthesis by human retinal pigment epithelial cells is mainly mediated via the particulate guanylyl cyclase pathway

BACKGROUND/AIMS: Cyclic 3',5'-guanosine monophosphate (cGMP), a central molecule in the phototransduction cascade, is also involved in a number of other physiological processes in the retina, like stimulating the absorption of subretinal fluid by activating the retinal pigment epithelium (RPE) cell pump. The aim of this study was to quantify cGMP synthesis by RPE cells and to investigate the role of two separate enzymatic pathways (soluble versus particulate guanylyl cyclase) in its production. METHODS: cGMP expression was evaluated by immunochemistry and radioimmunoassay following culture of the D407 RPE cell line in the presence of a nonselective phosphodiesterase inhibitor (IBMX), in combination with the particulate guanylyl cyclase stimulator atrial natriuretic peptide (ANP) or the soluble guanylyl cyclase stimulator sodium nitroprusside (SNP). RESULTS: Stimulation of the particulate guanylyl cyclase in RPE cells with ANP resulted in high intra- and extracellular cGMP levels. Stimulation of the soluble guanylyl cyclase by SNP resulted in a slight elevation of cGMP levels compared to controls. CONCLUSIONS: These results show that cultured human RPE cells are capable of producing cGMP and that most cGMP is generated following stimulation of the particulate guanylyl cyclase pathway