Alpinumisoflavone ameliorates choroidal neovascularisation and fibrosis in age-related macular degeneration in in vitro and in vivo models.

Age-related macular degeneration (AMD) is a major cause of vision loss in the elderly population. Anti-vascular endothelial growth factor (VEGF) antibody therapy is applicable to neovascularisation of AMD; however, the prevention of fibrosis after anti-VEGF monotherapy is an unmet medical need. Subretinal fibrosis causes vision loss in neovascular age-related macular degeneration (nAMD) even with anti-VEGF therapy. We report the anti-fibrotic and anti-neovascularisation effects of alpinumisoflavone (AIF), an isoflavonoid derived from unripe Maclura tricuspidata fruit, in in vitro and in vivo models. For in vitro study, we treated H2O2 or THP-1 conditioned media (TCM) following activation with phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS) in a human retinal pigment epithelial cell line (ARPE-19). Choroidal neovascularisation (CNV) was induced by laser photocoagulation in mice, immediately followed by intravitreal administration of 25 µg AIF. CNV area and fibrosis were measured 7 days after laser photocoagulation. AIF showed anti-fibrosis and anti-neovascularisation effects in both the models. The laser induced CNV area was reduced upon AIF administration in nAMD mouse model. Additionally, AIF decreased the levels of the cleaved form of crystallin alpha B (CRYAB), a chaperone associated with VEGF stabilisation and fibrosis. Our results demonstrate a novel therapeutic application of AIF against neovascularisation and fibrosis in nAMD.

USING RETeval SYSTEM FLICKER ELECTRORETINOGRAPHY FOR EVALUATION OF DENSE VITREOUS HEMORRHAGE.

PURPOSE: To determine whether the RETeval electroretinography (ERG) system can be used to evaluate eyes with dense vitreous hemorrhage (VH). METHODS: This retrospective case series study included 69 eyes of 69 patients with acute dense VH. Flicker ERGs were recorded by the RETeval system, an ERG device with adhesive skin electrodes. We evaluated the flicker ERG amplitudes in eyes with VH and the ratio of the VH eye amplitudes compared with the fellow eye amplitudes for each VH cause. RESULTS: In patients with rhegmatogenous retinal detachment, the amplitude ratios were extremely low (0.08 ± 0.03). To detect rhegmatogenous retinal detachment, the area under the receiver operating characteristic curve was 0.977 (95% confidence interval, 0.943-1.000) (best rhegmatogenous retinal detachment cutoff value, 0.14; sensitivity, 100.0%; and specificity, 95.4%). The flicker ERG amplitude was not significantly correlated with the initial visual acuity (ρ = -0.189, P = 0.120) but was positively correlated with the postoperative visual acuity in eyes with VH (ρ = -0.328, P = 0.006). CONCLUSION: The RETeval ERG system was found to be a useful diagnostic option in situations where dense VH precluded fundus examination or posterior vitreous detachment was indistinguishable from rhegmatogenous retinal detachment.

Development of a Fundus Image-Based Deep Learning Diagnostic Tool for Various Retinal Diseases.

Artificial intelligence (AI)-based diagnostic tools have been accepted in ophthalmology. The use of retinal images, such as fundus photographs, is a promising approach for the development of AI-based diagnostic platforms. Retinal pathologies usually occur in a broad spectrum of eye diseases, including neovascular or dry age-related macular degeneration, epiretinal membrane, rhegmatogenous retinal detachment, retinitis pigmentosa, macular hole, retinal vein occlusions, and diabetic retinopathy. Here, we report a fundus image-based AI model for differential diagnosis of retinal diseases. We classified retinal images with three convolutional neural network models: ResNet50, VGG19, and Inception v3. Furthermore, the performance of several dense (fully connected) layers was compared. The prediction accuracy for diagnosis of nine classes of eight retinal diseases and normal control was 87.42% in the ResNet50 model, which added a dense layer with 128 nodes. Furthermore, our AI tool augments ophthalmologist's performance in the diagnosis of retinal disease. These results suggested that the fundus image-based AI tool is applicable for the medical diagnosis process of retinal diseases.

Comparison of Retinal Layer Thickness and Capillary Vessel Density in the Patients with Spontaneously Resolved Acute Central Serous Chorioretinopathy.

We investigate retinal layer thickness and capillary vessel density (VD) in the patients with central serous chorioretinopathy (CSC) who recovered spontaneously and evaluate the correlation between the changes in these values and visual outcomes using swept-source optical coherence tomography (SS-OCT) and OCT angiography (OCTA). This retrospective case-control study included 34 eyes of 34 patients with spontaneously resolved acute CSC. The changes in retinal layer thickness and capillary VD were examined using SS-OCT and OCTA after complete resolution of subretinal fluid (SRF). The fellow eyes and 34 healthy eyes were used as controls. In the eyes with CSC, the outer retinal layer was significantly thinner than in the eyes of fellow and healthy controls. The foveal avascular zone area and VDs in the superficial and deep capillary plexus in the eyes with CSC were not significantly different from those in the eyes of fellow and healthy controls. The VD of the choriocapillaris in the eyes with CSC was significantly lower than that in the eyes of fellow and healthy controls. Correlation analyses revealed that the outer retinal layer thickness and initial visual acuity were positively correlated with the final visual acuity. Furthermore, the initial SRF area and height were negatively correlated with the outer retinal layer thickness after SRF resolution. Attenuation of outer retinal layer thickness and decreased VD of the choriocapillaris were observed in the eyes with spontaneously resolved acute CSC. The outer retinal layer thickness could be an important visual predictor of CSC.

Optical coherence tomography automated layer segmentation of macula after retinal detachment repair.

PURPOSE: To investigate the thickness of retinal layers and association with final visual acuity using spectral-domain optical coherence tomography (SD-OCT) in macular area of macula-off rhegmatogenous retinal detachment (RRD) patients after a successful macular re-attachment. METHODS: In retrospective study, a total 24 eyes with macula-off RRD were enrolled. All patients underwent vitrectomy to repair RRD. Outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor layer (PR), retinal pigment epithelium (RPE) thicknesses were measured by the Spectralis (Heidelberg Engineering, Heidelberg, Germany) SD-OCT with automated segmentation software. The relationship between the thicknesses of each retinal layer and postoperative logarithm of the minimum angle of resolution scale (LogMAR) visual acuity was analyzed. RESULTS: OPL and RPE thicknesses were not significantly different between the retinal detachment eyes and fellow eyes (P = 0.839, 0.999, respectively). The ONL and photoreceptor thickness were significantly thinner in the retinal detachment eyes (P <0.001 and 0.001, respectively). In the univariate regression analysis, preoperative best corrected visual acuity (BCVA), ONL thickness and photoreceptor thickness showed association with the postoperative BCVA (P = 0.003, <0.001 and 0.024, respectively). In final multiple linear regression model, ONL thickness was the only variable significantly associated with postoperative BCVA (P = 0.044). CONCLUSIONS: Segmented ONL and photoreceptor thickness of retinal detachment eyes were significantly thinner than fellow eyes. Segmental analysis of the retinal layer in macular region may provide valuable information for evaluation RRD. And ONL thickness can be used as a potential biomarker to predict visual outcome after RRD repair.

Direction-fixed and Direction-changing Positional Nystagmus in Ramsay Hunt Syndrome.

OBJECTIVES: To investigate the incidence of positional nystagmus (PN) using a head-roll test in patients with Ramsay Hunt syndrome with vertigo (RHS_V) and discuss possible mechanisms. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral academic medical center. PATIENTS: Twenty-eight patients with RHS_V were enrolled. MAIN OUTCOME MEASURE: Eye movements were recorded at positions of head roll to the right or left, and PN was classified as direction-fixed or direction-changing. Vestibular function tests including caloric test were performed. RESULTS: Direction-fixed nystagmus beating away from the affected side was the most common type of PN (61%), followed by direction-changing geotropic type (18%), direction-fixed nystagmus beating toward the affected side (14%), and direction-changing apogeotropic type (7%). The duration of nystagmus was longer than 60 seconds in all patients exhibiting direction-changing PN. Postcontrast T1-weighted internal auditory canal (IAC) magnetic resonance imaging showed enhancement of not only the facial and vestibulocochlear nerves, but also the inner ear structures or dura along the IAC, suggesting inflammatory changes within the labyrinthine membrane or IAC dura. CONCLUSION: Although direction-fixed PN was more commonly observed (75%), direction-changing PN was also observed in some RHS_V patients (25%). The mechanism of direction-changing PN may be, at least in part, explained by the alteration of specific gravity of the lateral semicircular canal cupula or endolymph due to inflammation in the inner ear membrane.