Narsing A. Rao

Background: The aim of this study was to determine the clinical significance of posterior choroidal thickness and vascular changes in the convalescent stage of Vogt-Koyanagi-Harada disease (VKH). Macular spectral domain optical coherence tomography (SD-OCT) images of 22 eyes of 13 consecutive patients with VKH at the convalescent stage were compared to 17 eyes of 9 age/sex/refraction-matched normal subjects. The choriocapillaris layer, medium choroidal vessels (Sattler's layer), and large choroidal vessels (Haller's layer) were assessed in foveal SD-OCT scans. The presence and the extent of disruption of outer retinal structures were also noted. Inner and outer choroid boundaries were manually drawn on horizontal raster SD-OCT scans, and choroidal thickness and volume maps were generated. Correlation analysis was run to assess the association of the above parameters in the VKH patients compared to the normal subjects. Results: In the eyes with convalescent stage of VKH, mean choroidal thickness in the foveal central subfield (200 ± 60 μm) was lower than in matched controls (288 ± 40 μm) (P < 0.0001). A thinner sub-macular choroid correlated with a lower visual acuity in uveitis eyes (Pearson correlation, r = -0.5089, P = 0.005). While the choriocapillaris layer was continuous and intact in all control eyes, various degrees of choriocapillaris loss were observed in 11 eyes (50%) with VKH (P < 0.0001). In these patients, the presence of outer retinal disruption was associated with a lower visual acuity (Spearman correlation, P < 0.001). Conclusions: The choroid is significantly thinner and the choriocapillaris layer is disrupted in the eyes with convalescent stage of VKH. Evaluation of the choriocapillaris in SD-OCT scans may be a useful surrogate marker for visual function in the convalescent stage of VKH.

Purpose: To evaluate temporal changes of epiretinal membrane (ERM) in uveitis. Methods: Six consecutive eyes with uveitis and ERM documented by spectral-domain – optical coherence tomography (SD-OCT) in 6 ± 1-month intervals during a 2-year follow-up (FU) period were included. Clinical information and SD-OCT data were noted at all FU visits. ERM thickness maps were created. The main outcome measures were BCVA, central subfield thickness (CST) and ERM thickness at baseline and FU visits. The correlation between ERM thickness and BCVA was analyzed. Results: Intraocular inflammation was inactive during the study period. Mean ERM thickness at the fovea increased 2.3 µm at 12-month and 2.4 µm at 24-month FU (p < .05). The increase in foveal ERM thickness was associated with foveal structural changes (p = .03). Visual acuity did not change during the FU. Conclusion: In well-controlled intraocular inflammation, increase in the ERM thickness does not lead to loss of vision in a 2-year FU period.

Unlike its constitutive isoforms, including neuronal and endothelial nitric oxide synthase, inducible nitric oxide synthase (iNOS) along with a series of cytokines are generated in inflammatory pathologic conditions in retinal photoreceptors. In this study, we constructed transgenic mice overexpressing iNOS in the retina to evaluate the effect of sustained, intense iNOS generation in the photoreceptor damage. For construction of opsin/iNOS transgene in the CMVSport 6 expression vector, the 4.4 kb Acc65I/Xhol mouse rod opsin promoter was ligated upstream to a 4.1 kb fragment encoding the complete mouse cDNA of iNOS. From the four founders identified, two heterozygote lines and one homozygote line were established. The presence of iNOS in the retina was confirmed and the pathologic role of iNOS was assessed by detecting nitrotyrosine products and apoptosis. Commercial TUNEL kit was used to detect DNA strand breaks, a later step in a sequence of morphologic changes of apoptosis process. The insertion and translation of iNOS gene were demonstrated by an intense single 130 kDa band in Western blot and specific immunolocalization at the photoreceptors of the retina. Cellular toxicity in the retinas of transgenic animals was detected by a post-translational modification product, tyrosine-nitrated protein, the most significant one of which was nitrated cytochrome c. Following the accumulation of nitrated mitochondrial proteins and cytochrome c release, marked apoptosis was detected in the photoreceptor cell nuclei of the retina. We have generated a pathologic phenotype with sustained iNOS overexpression and, therefore, high output of nitric oxide. Under basal conditions, such overexpression of iNOS causes marked mitochondrial cytochrome c nitration and release and subsequent photoreceptor apoptosis in the retina. Therefore, the modulation of pathways leading to iNOS generation or its effective neutralization can be of significant therapeutic benefit in the oxidative stress-mediated retinal degeneration, a leading cause of blindness.