Evolution and visual outcomes of outer foveolar lucency after surgery for large idiopathic macular hole.

PURPOSE: To explore the evolution of outer foveolar lucency (OFL) after vitrectomy and the correlation between OFL and visual acuity (VA) outcome in eyes with large idiopathic macular hole (IMH). METHODS: In this retrospective study, 244 eyes of 233 subjects with large IMH (diameter > 400 µm), who underwent vitrectomy, were included. Preoperative clinical data, postoperative optical coherence tomography (OCT) images, and VA at 1-, 4-, and 10-month visits were documented. The prevalence, incidence, and width of OFL and their correlation with postoperative VA were analyzed. RESULTS: The prevalence of OFL was 10.4% (24/231) at 1 month and significantly increased to 30.4% (55/181) at 4 months (P < 0.001) and 34.2% (25/73) at 10 months (P < 0.001). The incidence was 26.1% (40/153) and 22.0% (9/41) at 4 and 10 months, respectively. OFL appeared at 1 month while disappeared at 4 or 10 months in 8 eyes (50.0%). The presence of OFL at 1 month was negatively associated with IMH diameter (Nagelkerke R2 = 0.06; P = 0.02). Eyes with OFL at 4 months had better VA at their 4-month visit than eyes without OFL (P = 0.02). Eyes with early-developed OFLs had better VA at 10 months than those with later-developed ones (P = 0.02). Width of OFL was not associated with postoperative VA at any point. CONCLUSIONS: OFL is not rare in eyes with large IMH after surgery. It can occur gradually and remain during the 10-month follow-up. The presence of OFL appears to have no negative impact on the postoperative VA and it may represent the remodeling of foveal photoreceptors.

Hole diameter ratio for prediction of anatomical outcomes in stage III or IV idiopathic macular holes.

BACKGROUND: To determine whether preoperative hole diameter ratio (HDR) is a predictive factor for postoperative anatomical outcome for stage III or IV idiopathic macular holes (IMHs). METHODS: One-hundred and one eyes with stage III or IV IMH were included in this retrospective case series study. All cases were treated with vitrectomy combined with internal limiting membrane (ILM) peeling and room air tamponade. The macular hole (MH) minimum and maximum diameter was measured on preoperative optical coherence tomography (OCT) images. The HDR was defined as the minimum to maximum diameter ratio. RESULTS: Eighty-one eyes (80.2%) got a Type I closure after surgery (group A). Postoperative unclosed MHs were found in 20 eyes (19.8%) (group B). The preoperative minimal diameter (703.6 ± 116.1 µm vs. 597.6 ± 120.1 µm, P < 0.01) and HDR (0.6 ± 0.1 vs. 0.5 ± 0.1, P = 0.01) were both significantly smaller in postoperative closed eyes. The closure rate of IMHs with HDR < 0.6 was significantly higher than those with HDR ≥ 0.6 (90.2% vs. 65.0%P = 0.002) . CONCLUSIONS: Preoperative HDR < 0.6 is predictive for a good postoperative anatomical outcome in stage III or IV IMHs.

Effect of internal limiting membrane peeling on normal retinal function evaluated by microperimetry-3.

BACKGROUND: To evaluate the effect of internal limiting membrane (ILM) peeling surrounding macular holes (MH) for the function of retina by microperimetry-3(MP-3). METHODS: This is a prospective, cohort study which included patients with MHs who were treated by 23-gauge 3-port pars plana vitrectomy and ILM peeling with air tamponade. Color fundus photography, retinal optical coherence tomography and MP-3 were performed 1 week before, 1 and 4 months after the operation. In MP-3 examination, a customized follow-up pattern with 45 spots in the central 8° visual field was used. The spots corresponding to the retina surrounding macular holes were selected for comparison of pre- and post-operative function. RESULTS: We incuded 44 eyes of 44 patients with best corrected visual acuity (BCVA) of 1.06 ± 0.40 (logMAR). All eyes achieved an anatomical success at 4 months. BCVA significantly improved at 1 month (0.53 ± 0.30, P < 0.01) and 4 months (0.31 ± 0.24, P < 0.01), respectively. Mean retinal sensitivity (MRS, dB) of the retina surrounding macular hole was 23.46 ± 3.01 dB at baseline, and significantly increased at 1 month (26.25 ± 2.31 dB, u = - 4.88, P < 0.01) and 4 months (27.14 ± 2.45 dB, t = - 6.29, P < 0.01). Patients with increased MRS are significantly younger than those with deceased MRS (59.72 ± 3.22 years vs. 65.60 ± 8.19 years, P < 0.01). After ILM peeling, the increasing extent of MRS was significantly higher in inferior and nasal retina than in superior and temporal retina at 1 and 4 months (P < 0.05). CONCLUSION: ILM peeling in normal retina will not decrease the retinal function in a short-term after surgery.

COMPARISON OF 3 MM × 3 MM VERSUS 6 MM × 6 MM OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY SCAN SIZES IN THE EVALUATION OF NON-PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To evaluate the utility of different optical coherence tomography angiography scan protocols in evaluating retinal changes in non-proliferative diabetic retinopathy. METHODS: Patients were imaged with the RTVue XR Avanti OCT 3 mm × 3 mm and 6 mm × 6 mm "Angio Retina" scan protocols. Ability to clearly delineate the foveal avascular zone (FAZ), FAZ remodeling, microaneurysms, capillary nonperfusion, motion, and doubling artifacts were evaluated. RESULTS: Forty-six eyes from 27 patients were enrolled. Eighty-nine percent of 3 mm × 3 mm versus 59% of 6 mm × 6 mm scans clearly delineated the FAZ (P = 0.001). Eighty percent of 3 mm × 3 mm versus 43% of 6 mm × 6 mm scans demonstrated FAZ remodeling (P = 0.0002). Microaneurysms were detected by 57% of 6 mm × 6 mm and 35% of 3 mm × 3 mm scans (P = 0.003). Capillary nonperfusion was detected in 87% of 3 mm × 3 mm scans versus 89% of 6 mm × 6 mm scans (P = 0.99). No significant differences were noted in the incidence of artifacts between the scan sizes (motion artifact P = 0.29 and doubling artifact P = 0.29). CONCLUSION: 3 mm × 3 mm scan delineated FAZ and remodeling better than 6 mm × 6 mm scan, likely because of its higher scan density. 6 mm × 6 mm scans detected microaneurysms more readily than 3 mm × 3 mm, likely because of its larger scan area. There were utility for both 3 mm × 3 mm and 6 mm × 6 mm scans when evaluating these patients.

REDUCED GANGLION CELL VOLUME ON OPTICAL COHERENCE TOMOGRAPHY IN PATIENTS WITH GEOGRAPHIC ATROPHY.

PURPOSE: Geographic atrophy (GA) is the sequelae of macular degeneration. Automated inner retinal analysis using optical coherence tomography is flawed because segmentation software is calibrated for normal eyes. The purpose of this study is to determine whether ganglion cell layer (GCL) volume is reduced in GA using manual analysis. METHODS: Nineteen eyes with subfoveal GA and 22 controls were selected for morphometric analyses. Heidelberg scanning laser ophthalmoscope optical coherence tomography images of the optic nerve and macula were obtained, and the Viewing Module was used to manually calibrate retinal layer segmentation. Retinal layer volumes in the central 3-mm and surrounding 6-mm diameter were measured. Linear mixed models were used for statistics. RESULTS: The GCL volume in the central 3 mm of the macula is less (P = 0.003), and the retinal nerve fiber layer volume is more (P = 0.02) in patients with GA when compared with controls. Ganglion cell layer volume positively correlated with outer nuclear layer volume (P = 0.020). CONCLUSION: The patients with geographic atrophy have a small significant loss of the GCL. Ganglion cell death may precede axonal loss, and increased macular retinal nerve fiber layer volumes are not indicative of GCL volume. Residual ganglion cell stimulation by interneurons may enable vision in patients with GA.

Long Non-Coding RNA-MALAT1 Mediates Retinal Ganglion Cell Apoptosis Through the PI3K/Akt Signaling Pathway in Rats with Glaucoma.

BACKGROUND/AIMS: The aim of the present study is to investigate the effect of long non-coding RNA-MALAT1 (LncRNA-MALAT1) on retinal ganglion cell (RGC) apoptosis mediated by the PI3K/Akt signaling pathway in rats with glaucoma. METHODS: RGCs were isolated and cultured, and monoclonal antibodies (anti-rat Thy-1, Brn3a and RBPMS) were examined by immunocytochemistry. An overexpression vector MALAT1-RNA activation (RNAa), gene knockout vector MALAT1-RNA interference (RNAi), and control vector MALAT1-negative control (NC) were constructed. A chronic high intraocular pressure (IOP) rat model of glaucoma was established by episcleral vein cauterization. The RGCs were divided into the RGC control, RGC pressure, RGC pressure + MALAT1-NC, RGC pressure + MALAT1-RNAi and RGC pressure + MALAT1-RNAa groups. Sixty Sprague-Dawley (SD) rats were randomly divided into the normal, high IOP, high IOP + MALAT1-NC, high IOP + MALAT1-RNAa and high IOP + MALAT1-RNAi groups. qRT-PCR and western blotting were used to detect the expression levels of LncRNA-MALAT1 and PI3K/Akt. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and flow cytometry were used to detect RGC apoptosis. RESULTS: Immunocytochemistry revealed that the cultured RGCs reached 90% purity. Compared with the RGC pressure + MALAT1-NC group, the RGC pressure + MALAT1-RNAa group exhibited elevated expression levels of MALAT1, lower total protein levels of PI3K and Akt and decreased RGC apoptosis, while these expression levels were reversed in the RGC pressure + MALAT1-RNAi group. RGC numbers and PI3K/Akt expression levels in the high IOP model groups were lower than those in the normal group. In the high IOP + MALAT1-RNAa group, the mRNA and protein expression levels of PI3K/Akt were reduced but higher than those in the other three high IOP model groups. Additionally, RGC numbers in the high IOP + MALAT1-RNAa group were lower than those in the normal group but higher than those in the other three high IOP model groups. CONCLUSION: Our study provides evidence that LncRNA-MALAT1 could inhibit RGC apoptosis in glaucoma through activation of the PI3K/Akt signaling pathway.

OCT angiography quantifying choriocapillary circulation in idiopathic macular hole before and after surgery.

PURPOSE: To investigate the choriocapillary circulation in the macular area for eyes with unilateral idiopathic macular hole (IMH) before and after vitrectomy using optical coherence tomography angiography (OCTA). METHODS: A prospective study of 25 patients with unilateral IMH who underwent vitrectomy and 30 age- and sex-matched healthy controls were recruited. Choriocapillary circulation was measured by OCTA to obtain two measurements: flow area and parafovea vessel density. RESULTS: Flow area and parafovea vessel density of choriocapillaris in the macular area were significantly smaller and lower in IMH eyes than unaffected fellow eyes and healthy control eyes (p < 0.001), while no difference was found between unaffected fellow eyes and the healthy control eyes. One month after vitrectomy, the choriocapillary flow area and parafovea vessel density of IMH eyes significantly increased compared to the peroperative measurements (p < 0.001). Association analysis found that choriocapillary circulation measurements were negatively correlated with macular hole diameters in IMH eyes (p < 0.001), but was independent with best-corrected visual acuity (BCVA). CONCLUSIONS: The macular choriocapillary flow area and parafovea vessel density in IMH eyes were lower than those of normal controls. In addition, the choriocapillary circulation was negatively correlated with macular hole diameter. Our findings suggested that choroidal circulation in the macular area might be affected by the intact structure of the fovea.

INTEGRITY OF OUTER RETINAL LAYERS AFTER RESOLUTION OF CENTRAL INVOLVED DIABETIC MACULAR EDEMA.

PURPOSE: To evaluate the integrity of outer retina layers after resolution of central involved diabetic macular edema (DME) and to demonstrate the effect of various baseline factors for the final vision and final external limiting membrane (ELM) integrity. METHODS: Fifty-nine eyes of 48 patients with resolved DME were included. Several optical coherence tomography parameters including central subfield thickness, maximum foveal thickness, foveal center point thickness, and the extent of the ellipsoidal (ISe) layer and ELM damage were assessed at the time of DME and after resolution of DME. Eyes having laser scars near the fovea were excluded. Final visual acuity was classified as good (Snellen≥20/40, logarithm of the minimum angle of resolution ≤0.3) or impaired (Snellen <20/40, logarithm of the minimum angle of resolution >0.3) for the logistic regression analysis. Zero Inflated Poison Regression model was used to find the best predictors for post-treatment ELM damage. RESULTS: External limiting membrane and inner segment ellipsoidal band layers were disrupted in 16 eyes (27.2%) and 21 eyes (35.5%) at the final visit, respectively. Baseline ELM damage (p=0.001), baseline impaired vision (p= 0.013), and the most recent glycosylated hemoglobin level (p=0.018) were the best set of parameters for having impaired final visual acuity. Baseline vision, severity of diabetic retinopathy, absence of intravitreal injection, central subfield thickness, and history of extrafoveal macular laser (not within 1 mm of fovea) (p<0.001, for all parameters) were independent predictors for the final ELM damage. CONCLUSION: Outer retinal layers may be damaged even after complete resolution of DME, where inner segment ellipsoidal band layer damage appeared to be more common than ELM damage. Poorly controlled diabetic patients with damaged ELM and worse vision at the time of DME were more likely to have ELM damage and subsequent impaired vision after complete resolution of DME.

REPRODUCIBILITY OF VESSEL DENSITY MEASUREMENT WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN EYES WITH AND WITHOUT RETINOPATHY.

PURPOSE: To determine the intravisit and intervisit reproducibility of optical coherence tomography angiography measurements of macular vessel density in eyes with and without retinal diseases. METHODS: Fifteen healthy volunteers and 22 patients with retinal diseases underwent repeated optical coherence tomography angiography (Angiovue Imaging System, Optovue Inc) scans after pupil dilation on 2 separate visit days. For each visit day, the eyes were scanned twice. Vessel density defined as the proportion of vessel area with flowing blood over the total measurement area was calculated using Angiovue software. Intravisit and intervisit reproducibility were summarized as coefficient of variations and intraclass correlation coefficients were calculated from variance component models. RESULTS: The coefficient of variations representing the intravisit reproducibility of the superficial macular vessel density measurements for different quadrants on 3 mm × 3-mm scans varied from 2.1% to 4.9% and 3.4% to 6.8% for healthy and diseased eyes, respectively, and for the intervisit it was 2.9% to 5.1% and 4.0% to 6.8%, respectively. The coefficient of variations were lower in healthy eyes than in diseased eyes, lower for intravisit than for intervisit, lower on 3 mm × 3-mm scans than on 6 mm × 6-mm scans, and lower for paracentral subfields than for central subfield. CONCLUSION: The evidence presented here demonstrates good reproducibility of optical coherence tomography angiography for measurement of superficial macula vessel density in both healthy eyes and eyes with diabetic retinopathy without diabetic macular edema.

[Comparative analysis of the characteristics of bilateral rhegmatogenous retinal detachment].

OBJECTIVE: To investigate the characteristics of bilateral rhegmatogenous retinal detachment (RRD) in a hospital-based population. METHODS: Six hundred and three patients diagnosed with bilateral RRD in the Beijing Tongren Hospital between January 2000 and January 2014 were identified and included into the study. The clinical features including the age when retinal detachment occurrence, time interval between the occurrence of the bilateral RRDs, predisposing characteristics such as myopia, trauma, et al. were recorded by a chart review. RESULTS: Out of 8 283 patients treated for primary RRD in the study period, (7.30±2.45)%(603 patients) developed a RRD in the contralateral eye, with a mean age of (30.76 ± 15.31)years (range: 2-68) when the first RRD occurred. 4.8% of the patients primarily presented with a simultaneous bilateral RRD. Most RRD occurred firstly in the left eye (52.90%). Compared with the follow eye, the first RRD occurred with more macula detachment (P=0.03, OR: 1.59, 95%CI: 1.04-2.45) and retinal proliferation (P=0.04, OR: 1.57, 95% CI: 1.02-2.42), the visual outcome was more worse. Mean interval between the bilateral RRDs was (3.73±7.05) years (mean±standard deviation, range: 0-56 years) The younger, more severe symptoms of the firstly occurred RRD, the shorter interval between the bilateral RRD. Time interval between the bilateral RRD was shorter in those RRD firstly occurred with macula detachment, giant tears, horse-shoe tear, located in the temporal superior region, or with retinal degeneration. Compared with highly myopic eyes, the interval between the bilateral RRD were shorter in moderately myopic eyes. CONCLUSIONS: For patients newly diagnosed with RRD, regardless of age, are required to a lifelong follow-up for the contralateral eye, especially within one year. Patients who were young, with heavier symptoms, low to moderate myopia or present with retinal degeneration, should be closely followed up in a short time after the first RRD occurred.

Risk Factors of Myopic Shift among Primary School Children in Beijing, China: A Prospective Study.

OBJECTIVE: To evaluate factors associated with myopic shift among primary school children. METHODS: In a one-year prospective school-based study, 5052 children from ten schools were enrolled using a multi-stage random cluster approach. The baseline examination included non-cycloplegic auto-refractometry and questionnaire interview. Measurements were repeated at the follow-up. RESULTS: Among 5052 students at baseline investigated, 4292 students (85.0%) returned for the follow-up examination. The mean refractive error (-1.13±1.57 diopters) had changed -0.52±0.73 diopters from the baseline to the follow-up examination. 2170 (51.0%) had a rate of significant myopic shift (significant myopic shift is defined as the change of spherical equivalent of the refraction ≤ -0.50D between the follow-up and baseline measures). We confirmed that common associated factors (older age, parental myopia, lower refractive status at baseline, shorter reading distance and lower frequency of outdoor activities during class recesses) were associated with greater shift towards myopia. After controlling for age, sex, region of habitation, parental myopia and refractive status at baseline, greater shift towards myopia was independently associated with distance from near-work (OR=1.48 , 95% CI=1.26-1.74, P<0.001) and longer time outdoors for leisure (OR=0.87, 95% CI=0.78-0.97, P<0.013). CONCLUSION: Greater shift towards myopia was independently associated with modifiable factors (distance from near-work and longer time outdoors for leisure) might suggest that encouraging children to go outside for outdoor activities during class recess and after school may be a promising and feasible intervention against myopia development.

Primary extranodal marginal zone B-cell lymphoma with diffuse uveal involvement and focal infiltration of the trabecular meshwork: a case report and review of literature.

BACKGROUND: Primary extranodal marginal zone lymphoma (EMZL) of the uvea is a rare condition and diagnosis may be challenging. We aim to report the clinical, histopathologic and immunohistochemical findings in a case of primary EMZL with diffuse uveal involvement and focal infiltration of the trabecular meshwork. CASE PRESENTATION: A 38-year-old male presented with 2-year progressive vision loss in the right eye. Fundus examination showed choroidal thickening with diffuse retinal pigment epithelium (RPE) changes and inferior exudative retinal detachment. Ultrasonography revealed low-reflective masses with diffuse thickening of the choroid involving the optic nerve and orbit. Despite treatment with steroids, his symptoms progressed over time. One year later, visual acuity of the right eye markedly decreased to no light perception and enucleation was performed. Histopathological findings revealed infiltrates of malignant cells in the choroid, iris, ciliary body and trabecular meshwork. Immunohistochemistry confirmed the diagnosis of primary uveal EMZL. CONCLUSIONS: This is the first case reporting primary EMZL diffusely involving the uvea with focal infiltration of the trabecular meshwork.

Optical Coherence Tomographic Features and Visual Prognosis after Treatment for Idiopathic Choroidal Neovascularization.

BACKGROUND: The aim of this study was to determine whether pretreatment spectral-domain optical coherence tomographic (SD-OCT) features are associated with visual prognosis after treatment for idiopathic subfoveal choroidal neovascularization (ISCNV) with intravitreal ranibizumab. METHODS: We retrospectively evaluated SD-OCT images of eyes with ISCNV undergoing treatment with intravitreal ranibizumab with a mean follow-up of 7 months. RESULTS: This study included 22 patients (22 eyes) with a mean age of 32.7 ± 8.1 years. In univariate analysis, better final visual acuity expressed in logMAR units was significantly associated with a lower amount of pretreatment ellipsoid zone defects (p = 0.03; standardized correlation coefficient ß = 0.46) and a lower amount of pretreatment external limiting membrane (ELM) damage (p = 0.007; ß = 0.56). All other SD-OCT parameters were not significantly associated with final visual acuity. A higher improvement in visual acuity was marginally significantly associated with larger pretreatment ellipsoid zone defects (p = 0.049; ß = -0.43). CONCLUSIONS: The integrity of the outer retinal layers at baseline, in particular of the ELM, is of importance in predicting the final visual outcome in patients undergoing intravitreal medical therapy for ISCNV.

Subfoveal choroidal thickness change after intravitreal ranibizumab for idiopathic choroidal neovascularization.

PURPOSE: To investigate changes in subfoveal choroidal thickness (SFCT) after intravitreal injections of ranibizumab for idiopathic subfoveal choroidal neovascularization (ISCNV). METHODS: The prospective consecutive case series study included 16 patients with unilateral ISCNV. All eyes with ISCNV were treated with a single intravitreal injection of 0.5 mg ranibizumab followed by as-needed dosing. Subfoveal choroidal thickness was measured using enhanced depth imaging optical coherence tomography. RESULTS: The mean total follow-up time was 4.9 ± 1.5 months, and the follow-up after the last intravitreal ranibizumab injection was 4.4 ± 1.3 months. In the treated eyes, the SFCT decreased significantly from 354 ± 84 µm at baseline to 328 ± 79 µm at 1 month later (P < 0.001) and reincreased (P = 0.02) to 342 ± 75 µm at the final visit (P = 0.15 versus baseline value). Change in SFCT was marginally (P = 0.11) associated with the change in retinal foveal thickness. In the contralateral unaffected eyes, the SFCT did not change significantly during follow-up (P = 0.76). CONCLUSION: In patients with unilateral ISCNV, intravitreal ranibizumab therapy was associated with a thinning of an abnormally thick subfoveal choroid, marginally in association with a parallel decrease in retinal foveal thickness. It remained elusive whether the choroidal thinning was due to a direct pharmacological effect of ranibizumab or whether it was secondary due to the foveal retinal thinning. In view of the significant differences in SFCT between affected eyes and unaffected contralateral eyes at baseline and in view of the significant therapy-associated decrease in SFCT, the potential role of SFCT as an additional marker for the diagnosis and follow-up of ISCNV and other neovascular maculopathies may be examined in future studies.

Choroidal thickness in idiopathic subfoveal choroidal neovascularization.

PURPOSE: To evaluate choroidal thickness in patients with idiopathic choroidal neovascularization. METHODS: The observational case series study included patients who were consecutively diagnosed with idiopathic unilateral choroidal neovascularization as demonstrated by ophthalmoscopy, fluorescein angiography and enhanced depth imaging optical coherence tomography (EDI-OCT). Using EDI-OCT, choroidal thickness was measured at the fovea and at locations in a distance of 500, 1,000 and 1,500 µm temporal and nasal to the fovea. RESULTS: Mean subfoveal choroidal thickness was significantly (p = 0.002) thicker in the study group than in the control group (357 ± 99 vs. 316 ± 83 µm). In a parallel manner, the differences between the study group and the control group in choroidal thickness were significant for all other measurement points, except for the examination at 1,500 µm nasal to the fovea (p = 0.09). The results remained unchanged after adjusting for axial length and age. CONCLUSIONS: Idiopathic unilateral choroidal neovascularization is associated with a thickening of the choroid.

[Subfoveal choroidal thickness of Chinese aged over 50 years and patients with diabetes mellitus and glaucoma].

OBJECTIVE: To investigate the subfoveal choroidal thickness (SFCT) and its relationship to associated diseases, including diabetes mellitus, diabetic retinopathy, and glaucoma. METHODS: The population-based cross-sectional Beijing Eye Study 2011 included 3 468 individuals with a mean age of (64.6 ± 9.8) years. A detailed ophthalmic examination was performed including spectral-domain optical coherence tomography with enhanced depth imaging model (EDI SD-OCT). 246 patients with diabetes and 128 patients with glaucoma were enrolled in the study. Statistical analysis was performed by SPSS 20.0 to examined the mean values of SFCT and the prevalence rate of associated diseases; an univariate and multivariate linear regression to analyse the relationship between SFCT and ocular or general factors. RESULTS: Mean SFCT was (253.8 ± 107.4)µm. In multivariate analysis, SFCT was significantly associated with younger age (b = -4.12, P < 0.001), shorter axial length (b = -44.7, P < 0.001), male gender (b = -28.5, P < 0.001), deeper anterior chamber depth (b = 39.3, P < 0.001), thicker lens (b = 26.8, P < 0.001), flatter cornea (b = 46.0, P < 0.001) and better best corrected visual acuity (b = -48.4, P = 0.001). Mean SFCT in diabetes mellitus group was (266 ± 108) µm. In multivariate analysis, SFCT was significantly related to presence of diabetes mellitus (b = 21.2, P = 0.001); but neither presence (P = 0.61) nor stage (P = 0.14)of diabetic retinopathy was significantly associated with SFCT. Mean SFCT in glaucoma group was (201.4 ± 102.4.1) µm. Mean SFCT in glaucoma group was (201.4 ± 102.4.1) µm; for open angle glaucoma, mean SFCT was (210.1 ± 104.7) µm; for primary close angle glaucoma, mean SFCT was (184.2 ± 93.6 )µm. In multivariate analysis, SFCT was significantly associated with close angle glaucoma (b = -32.3, P = 0.04), but was not related to open angle glaucoma (P = 0.44). CONCLUSIONS: Mean SFCT was (253.8 ± 107.4)µm. SFCT was increased with age and myopic refractive error; and associated with male gender, anterior chamber depth, lens thickness, flatter cornea , best corrected visual acuity. SFCT in patients of diabetes mellitus was slightly thicker than normal people; but the presence and development of diabetic retinopathy were not related to SFCT. SFCT in patients with close angle glaucoma was thinner than control group; but for open angle glaucoma, SFCT was similar to the normal people.

Multi-Plexus Nonperfusion Area Segmentation in Widefield OCT Angiography Using a Deep Convolutional Neural Network.

Purpose: To train and validate a convolutional neural network to segment nonperfusion areas (NPAs) in multiple retinal vascular plexuses on widefield optical coherence tomography angiography (OCTA). Methods: This cross-sectional study included 202 participants with a full range of diabetic retinopathy (DR) severities (diabetes mellitus without retinopathy, mild to moderate non-proliferative DR, severe non-proliferative DR, and proliferative DR) and 39 healthy participants. Consecutive 6 × 6-mm OCTA scans at the central macula, optic disc, and temporal region in one eye from 202 participants in a clinical DR study were acquired with a 70-kHz OCT commercial system (RTVue-XR). Widefield OCTA en face images were generated by montaging the scans from these three regions. A projection-resolved OCTA algorithm was applied to remove projection artifacts at the voxel scale. A deep convolutional neural network with a parallel U-Net module was designed to detect NPAs and distinguish signal reduction artifacts from flow deficits in the superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Expert graders manually labeled NPAs and signal reduction artifacts for the ground truth. Sixfold cross-validation was used to evaluate the proposed algorithm on the entire dataset. Results: The proposed algorithm showed high agreement with the manually delineated ground truth for NPA detection in three retinal vascular plexuses on widefield OCTA (mean ± SD F-score: SVC, 0.84 ± 0.05; ICP, 0.87 ± 0.04; DCP, 0.83 ± 0.07). The extrafoveal avascular area in the DCP showed the best sensitivity for differentiating eyes with diabetes but no retinopathy (77%) from healthy controls and for differentiating DR by severity: DR versus no DR, 77%; referable DR (rDR) versus non-referable DR (nrDR), 79%; vision-threatening DR (vtDR) versus non-vision-threatening DR (nvtDR), 60%. The DCP also showed the best area under the receiver operating characteristic curve for distinguishing diabetes from healthy controls (96%), DR versus no DR (95%), and rDR versus nrDR (96%). The three-plexus-combined OCTA achieved the best result in differentiating vtDR and nvtDR (81.0%). Conclusions: A deep learning network can accurately segment NPAs in individual retinal vascular plexuses and improve DR diagnostic accuracy. Translational Relevance: Using a deep learning method to segment nonperfusion areas in widefield OCTA can potentially improve the diagnostic accuracy of diabetic retinopathy by OCT/OCTA systems.

The impact of intraocular pressure on optical coherence tomography angiography: A review of current evidence.

A scoping review of 45 peer-reviewed manuscripts involving intraocular pressure (IOP) change and concurrent optical coherence tomography angiography (OCTA) assessments was performed to aggregate knowledge, summarize major findings, and identify gaps in literature and methodology relating to the effect of IOP change on OCTA. Articles were identified through PubMed/Medline, Google Scholar, Cochrane, Web of Science, and article reference lists. A total of 838 results were identified, and 45 articles met the inclusion and exclusion criteria for detailed analysis. OCTA metrics including vessel density (VD), perfusion density, and flow density of the superficial capillary plexus and the radial peripapillary capillaries were analyzed in relation to relative temporal IOP changes. Overall, IOP changes were found to affect superficial vascular plexus (VD) measurements on OCTA, especially when IOP elevated above the physiologic normal range (10-21 mmHg). No significant association was found between diurnal IOP variation and OCTA metrics. Cataract surgery improved the whole-image signal strength and VD regardless of changes in IOP. Beta-blockers were associated with paradoxically reduced vessel density in normal tension glaucoma patients in two studies. Although glaucoma surgical intervention studies were inconsistent and limited by scan quality and low sample sizes, patients requiring glaucoma surgery exhibited attenuated postoperative superficial VD recovery despite significant IOP reductions with surgical intervention. In addition to ensuring near-perfect signal strength with minimal media opacities and controlling for high myopia, central corneal thickness, and the presence of retinopathy, clinicians should consider the statistically significant impact of IOP on OCTA metrics when interpreting results.

PDLIM1 inhibits cell migration and invasion in diabetic retinopathy via negatively regulating Wnt3a.

The injury of vascular endothelial cells is a crucial factor in the development of diabetic retinopathy (DR). PDLIM1 (a member of the PDZ and LIM protein family) has been reported to exert an essential function in vascular diseases. This study aimed to elucidate the role of PDLIM1 on retinal vascular endothelial cells in DR. Immunofluorescence staining was used to localize the expression of PDLIM1 in the mouse retina. In some tumor diseases, PDLIM1 has been reported to play a key role in regulating the Wnt pathway. However, no in-depth reports have been found in DR. Retinal capillary endothelial cells (RCECs) were treated with high-glucose and high-lipid (HG/HL) culture medium, and siRNA transfection to investigate the role of PDLIM1 in DR. PDLIM1 and Wnt3a expression was confirmed by qRT-PCR and western blotting. Flow cytometry, Transwell assay, and scratch assay were used to test the ability of cell apoptosis, migration, and invasion. PDLIM1 was mainly expressed in the retinal pigment epithelium (RPE), ganglion cell layer (GCL), inner plexus layer (IPL), and outer plexus layer (OPL). HG/HL increased Wnt3a levels and promoted cell's ability of apoptosis, migration, and invasion, which were reversed by the knockdown of PDLIM1. PDLIM1 was found to play a protective role in diabetic retinopathy by counter-regulating Wnt3a. PDLIM1 ameliorates cell apoptosis, migration, and invasion by negatively regulating Wnt3a in RCECs of DR, which suggests that PDLIM1 might be a promising therapeutic target for DR treatment.

Tetradecanoylphorbol-13-acetate (TPA) significantly increases AAV2/5 transduction of human neuronal cells in vitro.

Recombinant adeno-associated virus type 2 (AAV2) vectors have shown great promise in current ophthalmology clinical trials targeting gene delivery to the retinal pigment epithelium (RPE). To treat the majority of retinal diseases, however, gene delivery would need to be targeted to photoreceptor neurons of the outer retina. AAV2 pseudotyped with the AAV5 capsid (AAV2/5) has shown far greater transduction efficiency in photoreceptors compared to standard AAV2 vectors. For clinical trial applications using gene therapy, it is helpful to generate pre-clinical data in human cells wherever possible. There is however very little data, indeed some controversy, as to whether AAV2/5 can be used effectively in differentiated neurons in culture. In this study we show that transduction of the human neuroblastoma cell line SH-SY5Y with recombinant AAV2/5 expressing GFP is well tolerated. Furthermore, we explore the mechanism whereby exposure to retinoic acid (RA) and the phorbol ester 12-O-Tetradecanoylphorbol-13- acetate (TPA) can induce this cell line to differentiate into a stable population of human neurons, with significantly increased levels of AAV2/5 transduction. These observations may be helpful for assessing AAV2/5 vectors in vitro, particularly where it is necessary to generate pre-clinical data for clinical trials of gene therapy to the human central nervous system.