In HRPE cells, C3a induces decreased proteasome-mediated proteolytic activity, whereas in a mouse model of age-related RPE atrophy, the immunoproteasome was upregulated, indicating a possible role for complement-driven posttranslational alterations in proteasome activity in the cascade of pathologic events that result in AMD.

PurposeTo study a novel and fast optical coherence tomography (OCT) device for home-based monitoring in age-related macular degeneration (AMD) in a small sample yielding sparse OCT (spOCT) data and to compare the device to a commercially available reference device.MethodsIn this prospective study, both eyes of 31 participants with AMD were included. The subjects underwent scanning with an OCT prototype and a spectral-domain OCT to compare the accuracy of the central retinal thickness (CRT) measurements.ResultsSixty-two eyes in 31 participants (21 females and 10 males) were included. The mean age was 79.6 years (age range, 69–92 years). The mean difference in the CRT measurements between the devices was 4.52 μm (SD ± 20.0 μm; range, −65.6 to 41.5 μm). The inter- and intrarater reliability coefficients of the OCT prototype were both >0.95. The laser power delivered was <0.54 mW for spOCT and <1.4 mW for SDOCT. No adverse events were reported, and the visual acuity before and after the measurements was stable.ConclusionThis study demonstrated the safety and feasibility of this home-based OCT monitoring under real-life conditions, and it provided evidence for the potential clinical benefit of the device.Translational RelevanceThe newly developed spOCT is a valid and readily available retina scanner. It could be applied as a portable self-measuring OCT system. Its use may facilitate the sustainable monitoring of chronic retinal diseases by providing easily accessible and continuous retinal monitoring.

PurposeFeasibility testing of a novel volume renders technology to display optical coherence tomography data (OCT) in a virtual reality (VR) environment.MethodsA VR program was written in C++/OpenGL to import and display volumetric OCT data in real time with 180 frames per second using a high-end computer and a tethered head-mounted display. Following exposure, participants completed a Simulator Sickness Questionnaire (SSQ) to assess for nausea, disorientation, and oculomotor disturbances. A user evaluation study of this software was conducted to explore the potential utility of this application.ResultsFifty-seven subjects completed the user testing (34 males and 23 females). Mean age was 48.5 years (range, 21–77 years). Mean acquired work experience of the 35 ophthalmologists (61.40%) included in the group was 15.46 years (range, 1–37 years). Twenty-nine participants were VR-naïve. The SSQ showed a mean total score of 5.8 (SD = 9.44) indicating that the system was well tolerated and produced minimal side effects. No difference was reported between VR-naïve participants and experienced users. Overall, immersed subjects reported an enjoyable VR-OCT presence effect.ConclusionsA usable and satisfying VR imaging technique was developed to display and interact with original OCT data.Translational RelevanceAn advanced high-end VR image display method was successfully developed to provide new views and interactions in an ultra high-speed projected digital scenery using point-cloud OCT data. This represents the next generation of OCT image display technology and a new tool for patient engagement, medical education, professional training, and telecommunications.

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Purtscher-like retinopathy, a rare manifestation of systemic thrombotic microangiopathy, is a potentially visually debilitating condition with no effective proven treatment. Distinct pathogenic pathways have been proposed as etiological factors. We revisit the etiology of Purtscher-like retinopathy based on the rapid response and profound visual improvement after initiation of systemic intravenous eculizumab, an inhibitor of the complement cascade, in a patient with Purtscher-like retinopathy secondary to familial atypical hemolytic uremic syndrome (aHUS) due to a mutation in complement factor H. We hypothesize that the efficacy of eculizumab in this patient provides evidence for pathogenic events in the retina similar to those encountered in the renal microvasculature of aHUS patients, namely complement-mediated thromboembolization as a result of activation of the complement cascade in endothelial cells with release of tissue factor and development and amplification of a procoagulant state. To the best of our knowledge, this is the first report in the literature of eculizumab as an effective therapeutic strategy in Purtscher-like retinopathy.

Emerging evidence suggests that dysfunction of the ubiquitin-proteasome system is involved in the pathogenesis of numerous senile degenerative diseases including retinal disorders. The aim of this study was to assess whether there is a link between proteasome regulation and retinal pigment epithelium (RPE)-mediated expression of extracellular matrix genes. For this purpose, human retinal pigment epithelial cells (ARPE-19) were treated with different concentrations of transforming growth factor-β (TGFβ), connective tissue growth factor (CTGF), interferon-γ (IFNγ) and the irreversible proteasome inhibitor epoxomicin. First, cytotoxicity and proliferation assays were carried out. The expression of proteasome-related genes and proteins was assessed and proteasome activity was determined. Then, expression of fibrosis-associated factors fibronectin (FN), fibronectin EDA domain (FN EDA), metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinases-1 (TIMP-1) and peroxisome proliferator-associated receptor-γ (PPARγ) was assessed. The proteasome inhibitor epoxomicin strongly arrested cell cycle progression and down-regulated TGFβ gene expression, which in turn was shown to induce expression of pro-fibrogenic genes in ARPE-19 cells. Furthermore, epoxomicin induced a directional shift in the balance between MMP-2 and TIMP-1 and was associated with down-regulation of transcription of extracellular matrix genes FN and FN-EDA and up-regulation of the anti-fibrogenic factor PPARγ. In addition, both CTGF and TGFβ were shown to affect expression of proteasome-associated mRNA and protein levels. Our results suggest a link between proteasome activity and pro-fibrogenic mechanisms in the RPE, which could imply a role for proteasome-modulating agents in the treatment of retinal disorders characterized by RPE-mediated fibrogenic responses.

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Background: Detection of a relative afferent pupillary defect (RAPD) by the swinging-light test can be challenging in clinical practice (dark eyes, anisocoria). We developed a new method of RAPD quantification based on the recording of the Infrared Pupillary Asymmetry (IPA) with a standard optical coherence tomography (OCT) device. Methods:The diagnostic value of the IPA for detection of the RAPD was determined by Receiver Operating Characteristic (ROC) curves, Area Under the Curve (AUC).Results: Twenty-nine subjects were included in this study (17 controls, 12 unilateral optic neuropathies). The IPA was significantly greater in unilateral optic neuropathies (0.39) compared to controls (0.18, p = 0.001). The diagnostic value was good with a ROC-AUC of 0.843. Importantly, the IPA correlated significantly with the inter-eye difference of the macular ganglion cell-inner plexiform layer (mGCIPL) thickness (R = 0.53, p = 0.01). Assessment of the IPA took less than 30 seconds. Conclusion:Present data show that the IPA is a practical and rapid test that can be applied in a clinical setting. The IPA may be a valuable functional outcome measure for clinical trials, complementing structural retinal OCT data in a biological meaningful way. The IPA should be further investigated for suitability for optic neuritis treatment trials.