Purpose: Keratoconus (KC) can lead to severe vision loss, impacting daily life. The etiology of KC is not yet clear, and early diagnosis and treatment are crucial for prognosis. This study aimed to explore basement membrane (BM)-related gene signatures for the diagnosis and therapy of KC and provide novel insights into its pathogenesis. Methods: Based on the public datasets GSE112155 and GSE151631 in the GEO database, we obtained the differentially expressed genes (DEGs) of KC and downloaded BM-related genes based on the GeneCards database. Through a combination of bioinformatics methods, primarily weighted gene coexpression network analysis (WGCNA) and machine learning such as random forest (RF) and support vector machine (SVM), BM-related genes were identified as biomarkers for KC diagnosis. Subsequently, we further validated these findings using unsupervised clustering analysis, nomogram, and ROC curve analysis. Results: Through the analysis of two KC-related datasets, 227 DEGs were screened out and intersected with BM-related genes to obtain 195 intersecting genes. By applying WGCNA and two machine learning algorithms, we identified four key genes, namely, CRY2, RNF19B, PPP1R18, and PFKFB3. These genes were significantly expressed in the normal control group. According to the ROC analysis, all four genes demonstrated excellent diagnostic performance in internal validation, with AUC values all exceeding 0.8. In external validation, CRY2, RNF19B, and PPP1R18 showed good predictive performance, each with AUC values greater than 0.6. Unsupervised clustering and nomogram also supported the good diagnostic capabilities of these genes. In addition, unsupervised clustering analysis also indicated that these four genes were mainly distributed in subtype A of KC. Immune infiltration analysis and functional enrichment analysis further suggested that immune inflammation, metabolism, and apoptosis were also involved in KC. Conclusion: Using bioinformatics analysis, we found three novel hub genes, CRY2, RNF19B, and PPP1R18, which are beneficial for the diagnosis and therapy of KC.

Translocator protein (18 kDa) (TSPO) plays an important role in retinal neuroinflammation in the early stage of diabetic retinopathy (DR). Studies have found that a FGF1 variant (FGF1ΔHBS) with reduced proliferative potency exerts excellent anti-inflammatory effects and potential therapeutic value for diabetic complications. In this study, intravitreal injection of FGF1ΔHBS was administrated every week for one month in db/db mice, which are genetically predisposed to develop type 2 diabetes mellitus and early retinopathy. Changes in retinal function and structure in the animal models were detected by electrophysiology (ERG) and optical tomography coherence (OCT). TSPO expression and retinal inflammation were analyzed by immunofluorescence, Western blot and real-time qPCR. In the retina of T2D (db/db) mice, FGF1 was significantly down-regulated while FGFR1 was up-regulated (both p < 0.05). TSPO and retinal inflammatory factors were all up-regulated. TSPO and FGFR1 were mainly co-stained in the inner retina. After FGF1ΔHBS treatment, ERG showed that the total amplitude of dark-adapted b-wave and oscillating potentials (Ops) was significantly improved, and OCT showed that the thickness of the retina around the optical nerve head was significantly preserved in T2D mice (all p < 0.05). The TSPO signal was significantly suppressed by FGF1ΔHBS. The activation of NF-κB p65 and the expression of inflammatory factors such as TNF-α, IL-1β, IL-6, COX-2, MIP-1α, and iNOS were all significantly down-regulated (all p < 0.05). Collectively, our current data demonstrated that intravitreal FGF1ΔHBS treatment can effectively inhibit retinal inflammation via suppressing TSPO signal and to preserve retinal function and structure in a T2D mouse model.

BackgroundWhile several studies have noted a higher SII correlates with multiple diseases, research on the association between SII and cataract remains limited. Our cross-sectional study seeks to examine the association between SII and cataract among outpatient US adults.MethodsThis compensatory cross-sectional study utilized NHANES data from 1999 to 2008 cycles, conducting sample-weighted multivariate logistic regression and stratified analysis of subgroups.ResultsAmong 11,205 adults included in this study (5,571 [46.2%] male; 5,634 [53.8%] female), 2,131 (15.2%) had cataract and 9,074 (84.8%) did not have cataract. A fully adjusted model showed that SII higher than 500 × 109/L was positively correlated with an increased risk of cataracts among women (OR, 1.27; 95% CI, 1.02–1.59) (p = 0.036). However, no difference was found in the men subgroup, and there was no significant interaction between SII and sex.ConclusionOur results indicated that a SII higher than 500 × 109/L was positively correlated with an increased risk of cataracts in women. This study is the first to specifically investigate the impact of a high SII on cataract risk in outpatient adults in the United States. By effectively addressing inflammation, it is possible to mitigate cataract progression and significantly enhance patient outcomes.

Purpose Myopia, especially high myopia (HM), represents a widespread visual impairment with a globally escalating prevalence. This study aimed to elucidate the genetic foundations associated with early-onset HM (eoHM) while delineating the genetic landscape specific to Shaanxi province, China.Methods A comprehensive analysis of whole-exome sequencing was conducted involving 26 familial trios displaying eoHM. An exacting filtration protocol identified potential candidate mutations within acknowledged myopia-related genes and susceptibility loci. Subsequently, computational methodologies were employed for functional annotations and pathogenicity assessments.Results Our investigation identified 7 genes and 10 variants associated with HM across 7 families, including a novel mutation in the ARR3 gene (c.139C>T, p.Arg47*) and two mutations in the P3H2 gene (c.1865T>C, p.Phe622Ser and c.212T>C, p.Leu71Pro). Pathogenic mutations were found in syndromic myopia genes, notably encompassing VPS13B, TRPM1, RPGR, NYX and RP2. Additionally, a thorough comparison of previously reported causative genes of syndromic myopia and myopia risk genes with the negative sequencing results pinpointed various types of mutations within risk genes.Conclusions This investigation into eoHM within Shaanxi province adds to the current understanding of myopic genetic factors. Our results warrant further functional validation and ocular examinations, yet they provide foundational insights for future genetic research and therapeutic innovations in HM.

The accuracy of intraocular lens (IOL) calculations is one of the key indicators for determining the success of cataract surgery. However, in highly myopic patients, the calculation errors are relatively larger than those in general patients. With the continuous development of artificial intelligence (AI) technology, there has also been a constant emergence of AI-related calculation formulas. The purpose of this investigation was to evaluate the accuracy of AI calculation formulas in calculating the power of IOL for highly myopic patients. We searched the relevant literature through August 2023 using three databases: PubMed, EMBASE, and the Cochrane Library. Six IOL calculation formulas were compared: Kane, Hill-RBF, EVO, Barrett II, Haigis, and SRK/T. The included metrics were the mean absolute error (MAE) and percentage of errors within ± 0.25 D, ± 0.50 D, and ± 1.00 D. The results showed that the MAE of Kane was significantly lower than that of Barrett II (mean difference = − 0.03 D, P = 0.02), SRK/T (MD = − 0.08 D, P = 0.02), and Haigis (MD = − 0.12 D, P < 0.00001). The percentage refractive prediction errors for Kane at ± 0.25 D, ± 0.50 D, and ± 1.00 D were significantly greater than those for SRK/T (P = 0.007, 0.003, and 0.01, respectively) and Haigis (P = 0.009, 0.0001, and 0.001, respectively). No statistically significant differences were noted between Hill-RBF and Barret, but Hill-RBF was significantly better than SRK/T and Haigis. The AI calculation formulas showed more accurate results compared with traditional formulas. Among them, Kane has the best performance in calculating IOL degrees for highly myopic patients.

The clinical benefits of diquafosol tetrasodium (DQS), a hydrophilic P2Y2 receptor agonist for dry eye, have been hindered by a demanding dosing regimen. Nevertheless, it is challenging to achieve sustained release of DQS with conventional drug delivery vehicles which are mainly designed for hydrophobic small molecule drugs. To address this, we developed an affinity hydrogel for DQS by taking advantage of borate-mediated dynamic co-valent complexation between DQS and hydroxypropyl guar. The resultant formulation (3% DQS Gel) was characterized by sustained release, low corneal permeation, and extended ocular retention, which were desirable attributes for ocular surface drug delivery. Both in vitro and in vivo studies had been carried out to verify the biocompatibility of 3% DQS Gel. Using corneal fluorescein staining, the Schirmer's test, PAS staining, quanti-tative PCR and immunohistological analyses as outcome measures, the superior therapeutic effects of 3% DQS Gel over PBS, the hydrogel vehicle and free DQS were demonstrated in a mouse dry eye model. Our DQS delivery strategy reported herein is readily applicable to other hydrophilic small molecule drugs with cis-diol moieties, thus providing a general solution to improve clinical outcomes of numerous diseases.

Purpose:To evaluate the influence of intraocular pressure (IOP) measurement while wearing bandage contact lens (BCL) and the effect of Pentacam and Corvis ST's correction systems. Methods:It was a prospective comparative study. Forty healthy subjects (40 eyes) were included in this study. Eyes were measured using noncontact tonometer (NCT), Corvis ST, and Pentacam before and after wearing BCL. Pentacam's five correction formulas (Ehlers formula, Shah formula, Dresden formula, Kohlhaas formula, Orssengo/Pye formula) and Corvis ST's correction formulas (Ehlers formula and biomechanical corrected formula) were used to correct the IOP values before and after BCL wearing. The IOP values were compared, and the correction effect of different systems were evaluated. Results:The mean age of the subjects was 24.4 ± 0.60 years. The mean IOP obtained by NCT was 14.8 ± 3.2 mmHg before BCL wearing and was 15.7 ± 3.4 mmHg after BCL wearing. The mean IOP was significantly increased after BCL wearing (0.9 ± 2.9 mmHg, P=0.05). Four of the five Pentacam's correction formulas (except Kohlhaas formula) showed no significant difference in the mean corrected IOP values before and after BCL wearing (all P > 0.05). The mean IOP obtained by Corvis ST was 13.7 ± 2.8 mmHg before BCL wearing and was 15.0 ± 4.0 mmHg after BCL wearing. The mean IOP was significantly increased after BCL wearing (1.3 ± 2.4 mmHg, P < 0.05). Corvis ST's correction formula (Ehlers formula other than biomechanical corrected formula) showed no significant difference in the mean corrected IOP values before and after BCL wearing (P > 0.05). Conclusion:The IOP measurements over BCL by NCT and Corvis ST was found to be increased. The correction systems of Pentacam (Ehlers formula, Shah formula, Dresden formula, and Orssengo/Pye formula) and Corvis ST (Ehlers formula) are useful in correcting the IOP measuring deviation induced by BCL wearing.

Introduction: The macular morphologic and microvascular changes in children with pseudophakia after pediatric cataract surgery remain unknown. The aim of this study was to analyze macular morphologic and microvascular remodeling in children with pseudophakia after pediatric cataract surgery using optical coherence tomography angiography (OCTA). Methods: Consecutive cases between December 1, 2018, and November 31, 2020 were recruited. Sixty-one participants (31 pseudophakic children and 30 healthy controls) met the inclusion criteria and were included for final analysis. OCTA was used to measure macular vascular density, the foveal avascular zone (FAZ), and macular thickness. The parameters were compared between pseudophakic and healthy eyes using binary logistic regression, with adjustment for the effect of refractive error, age, and axial length. Results: Compared with normal eyes, a significantly reduced area of the FAZ (p = 0.042), increased superficial foveal vascular density (p = 0.033), and increased inner and outer foveal thickness (p = 0.034 and 0.029, respectively) were noted in pseudophakic eyes. The deep parafoveal vascular density was generally lower in eyes with cataracts (p ≤ 0.044). The inner foveal thickness was positively correlated with the superficial foveal vascular density (r = 0.889, p < 0.001) and negatively correlated with the area of the FAZ (r = −0.903, p < 0.001). The outer foveal thickness was positively correlated with the deep foveal vascular density (r = 0.399, p = 0.002). Conclusions: Morphological and microvascular remodeling in children with previous pediatric cataract indicates foveal underdevelopment. The underlying mechanism requires further investigation.

Purpose:Autophagy plays an important role in balancing the inflammatory response to restore homeostasis. The aim of this study was to explore the mechanism by which trehalose suppresses inflammatory cytokines via autophagy activation in primary human corneal epithelial cells (HCECs) exposed to hyperosmotic stress.Methods:An in vitro dry eye model was used in which HCECs were cultured in hyperosmolar medium with the addition of sodium chloride (NaCl). Trehalose was applied in different concentrations. The levels of TNF-α, IL-1β, IL-6, and IL-8 were detected using RT-qPCR and ELISA. Cell viability assays, immunofluorescent staining of LC3B, and western blots of Beclin1, Atg5, Atg7, LC3B, and P62 were conducted. The key factors in upstream signaling pathways of autophagy activation were measured: P-Akt, Akt, and transcription factor EB (TFEB).Results:Trehalose reduced the proinflammatory mediators TNF-α, IL-1β, IL-6, and IL-8 in primary HCECs at 450 mOsM. This effect was osmolarity dependent, and a level of 1.0% trehalose showed the most suppression. Trehalose promoted autophagosome formation and autophagic flux, as evidenced by increased production of Beclin1, Atg5, and Atg7, as well as higher LC3B I protein turnover to LC3B II, with decreased protein levels of P62/SQSTM1. The addition of 3-methyladenine blocked autophagy activation and increased the release of proinflammatory cytokines. Trehalose further activated TFEB, with translocation from cytoplasm to the nucleus, but diminished Akt activity.Conclusions:Our findings demonstrate that trehalose, functioning as an autophagy enhancer, suppresses the inflammatory response by promoting autophagic flux via TFEB activation in primary HCECs exposed to hyperosmotic stress, a process that is beneficial to dry eye.

Abstract Purpose To assess the repeatability and reproducibility of swept-source optical coherence tomography (SS-OCT) and Scheimpflug system and evaluate the agreement between the two systems in measuring multiple corneal regions in children. Methods Pachymetric and keratometric maps for both systems were evaluated. Central, midperipheral and peripheral corneal thickness (CT), keratometry and astigmatism power vectors were recorded. The three outcomes yielded by the same observer were used to assess intraobserver repeatability. The differences in the mean values provided by each observer were used to evaluate interobserver reproducibility. Within-subject standard deviation, test-retest repeatability (TRT) and coefficient of variation (CoV) were used to analyze the intraobserver repeatability and interobserver reproducibility. Paired T-test and Bland-Altman were used to appraise interdevice agreement. Results Seventy-eight eyes of 78 children were included. The CoV was ≤2.12 and 1.10%, respectively, for repeatability and reproducibility. TRT and CoV were lower for central and paracentral CT measurements than for peripheral measurements. The SS-OCT device generated higher precision when acquiring CT data, whereas Scheimpflug system showed higher reliability when measuring corneal keratometry. Although the CT readings measured using SS-OCT were significantly thinner than Scheimpflug device (P < 0.001), the central and thinnest CT values were still of high agreement. The interdevice agreement of keratometry measurement was high for the central corneal region and moderate for the paracentral and peripheral areas. Conclusions The precision of CT measurements by SS-OCT was higher, while the reliability of keratometry measurements by the Scheimpflug system was higher in children. Apart from the measured values in the central corneal region, the thickness and keratometry readings should not be considered interchangeable between the two systems.

PURPOSE:To explore the pathological features and clinical significance of three types of neovascularization elsewhere (NVE) in proliferative diabetic retinopathy.METHODS:Neovascularization elsewhere was classified based on the origins and morphologic features using fluorescein angiography and angiographic and structural optical coherence tomography. The topographical distribution, vitreoretinal interface, and responsiveness to panretinal photocoagulation were compared among three types of NVE.RESULTS:One hundred and twenty-seven NVEs were classified into three types. Type 1 NVE was concentrated along or adjacent to vascular arcades; Type 2 was distributed more peripherally than were Types 1 and 3 NVE. The arch bridge-like vitreoretinal interface accounted for 79% of Type 1 NVE. The flat and flat-forward vitreoretinal interface accounted for 95% and 100% in Type 2 and Type 3 NVE, respectively. At 3 months after panretinal photocoagulation, the regression rates for Types 1, 2, and 3 NVE were 82%, 100%, and 80%, respectively. Type 2 NVE showed best regression rate after panretinal photocoagulation (both P < 0.01).CONCLUSION:Three types of NVE determine the distinctly topographical distributions, vitreoretinal interface features, and differential responsiveness to panretinal photocoagulation treatment. This new concept may have important clinical implications in assessing the treatment and prognosis of proliferative diabetic retinopathy.

PURPOSE To assess the repeatability of epithelial, stromal, and total corneal thickness measurements with spectral-domain optical coherence tomography (SD-OCT; RTVue-XR; Optovue, Inc., Fremont, CA) in patients with myopia, keratoconus, and corneas after transepithelial photorefractive keratectomy (PRK), small incision lenticule extraction (SMILE), and femtosecond laser-assisted in situ keratomileusis (FS-LASIK). METHODS A total of 352 eyes of 352 patients (75 myopic, 68 post-transepithelial PRK, 61 post-SMILE, 75 post-FS-LASIK, 20 mild keratoconus, and 53 advanced keratoconus eyes) were included. The epithelial, stromal, and total corneal thickness were recorded from the pachymetric map in the following four zones: (1) central 2-mm region, (2) eight paracentral regions within 2- to 5-mm diameter, (3) eight midperipheral regions within 5- to 7-mm diameter, and (4) eight peripheral regions within 7- to 9-mm diameter. Three successive scans were performed to evaluate the repeatability. RESULTS For all zones up to 9-mm diameter, the coefficient of variation (CoV) for epithelial thickness measurements ranged from 1.7% to 3.5% for myopia, 2.6% to 6.2% for post-transepithelial PRK, 2.3% to 4.7% for post-SMILE, 4.0% to 6.3% for post-FS-LASIK, 2.5% to 6.2% for mild keratoconus, and 3.5% to 8.0% for advanced keratoconus. The CoV for stromal and total thickness measurements ranged from 0.2% to 2.0% for myopia, 0.7% to 4.2% for post-transepithelial PRK, 0.3% to 2.4% for post-SMILE, 0.3% to 1.9% for post-FS-LASIK, 0.6% to 3.0% for mild keratoconus, and 1.0% to 5.9% for advanced keratoconus. CONCLUSIONS RTVue-XR SD-OCT showed excellent repeatability when generating the pachymetric map in myopic eyes. Measurements, especially for epithelial thickness, were relatively more variable for corneas with keratoconus and those having undergone keratorefractive surgery. [J Refract Surg. 2019;35(9):600-605.].

The complete disassembly of nuclear is the most challenging step in hard cataract surgery through microincision. The classic phaco chop technique often does not succeed, resulting in incomplete nuclear segmentation. The authors describe a technique to improve the efficacy and safety of the initial chopping. The consecutive drilling combined with phaco chop technique was devised for very hard cataract through a microincision of 1.8–2.2 mm. 3–4 holes are consecutively drilled into the endonucleus with the phaco tip bevel down, at an angle of approximate 60 degrees and depth of approximately two-thirds of the lens thickness. The initial drilling approaches the capsulorhexis edge and the last drilling approaches the lens geometric center. The nucleus is deeply impaled with the last drilling and firmly engaged with high vacuum, and then chopped with chopper centripetally from the lens equator. The chopper and phaco tip are spread apart laterally after they approach at the center of the nucleus, to create a complete fracture across the entire nucleus. This technique has been adopted in 80 eyes of 65 patients with cataract harder than nuclear opalescence 5 on the Lens Opacities Classification System III scale or mature white cataract with a hard nucleus in the past 12 months. In all cases, full thickness segmentation of the hard nuclear including the posterior plate was achieved with this consecutive drilling combined with phaco chop technique. Phacoemulsification and intracapsular implantation of intraocular lens was safely performed in each case. No intraoperative complication such as iris injury, anterior capsule tears, zonulysis or posterior capsule rupture with vitreous loss occurred during surgery. No postoperative complication such as fibrin formation, synechias, severe endothelial cell loss, or endophthalmitis was observed in any case at 6 months postoperatively. The technique is an efficient, safe, simple, and swift procedure for full-thickness nuclear segmentation, delivering advantage of microincisional phacoemulsifcation for hard cataract with few ocular complications.

Purpose: To describe the clinical outcomes of traumatic aphakic eyes with corneal astigmatism after using a novel technique for toric intraocular lens suture fixation. Methods: In total, 12 eyes of 12 patients who underwent a new scleral suture fixation technique of one-piece toric intraocular lens (SN6AT series, Alcon Inc., TX, USA) were included in our retrospective study. Preoperative patient status, postoperative visual acuity and refractive outcomes, postoperative intraocular lens rotation, tilt, decentration, and complications were analyzed. Results: The mean follow-up was 11.6 ± 1.0 months. The mean preoperative best-corrected visual acuity was 0.55 ± 0.32 in the logarithm of minimum angle of resolution equivalent; the postoperative best-corrected visual acuity was 0.45 ± 0.34. The mean preoperative total corneal astigmatism was 2.51 ± 1.67 D. The mean postoperative residual astigmatism was 0.77 ± 0.54 D. The mean intraocular lens rotation was 3.33° ± 1.37° (range, 1°–6°). The mean intraocular lens tilt in horizontal direction was 3.64° ± 1.02° (range, 2.6°–6.3°) and in vertical direction it was 3.19° ± 1.07 ° (range, 1.6°–5.2°). The mean intraocular lens decentration in horizontal direction was 0.14 ± 0.03 mm (range, 0.089–0.192 mm) and in vertical direction it was 0.15 ± 0.02 mm (range, 0.113–0.181 mm). One patient had mild vitreous hemorrhage and two other patients had high postoperative residual sphere and astigmatism, respectively. But no other serious complications were observed. Conclusion: Scleral suture fixation of foldable toric intraocular lens to correct corneal astigmatism can be a safe and effective alternative technique to manage traumatic aphakic eyes that lack adequate capsular support.

X-linked juvenile retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding retinoschisin (RS1), which leads to a significant proportion of visual impairment and blindness. To develop personalized genome editing based gene therapy, knock-in animal disease models that have the exact mutation identified in the patients is extremely crucial, and that the way which genome editing in knock-in animals could be easily transferred to the patients. Here we recruited a family diagnosed with XLRS and identified the causative mutation (RS1, p.Y65X), then a knock-in mouse model harboring this disease-causative mutation was generated via TALEN (transcription activator-like effector nucleases). We found that the b-wave amplitude of the ERG of the RS1-KI mice was significantly decreased. Moreover, we observed that the structure of retina in RS1-KI mice has become disordered, including the disarray of inner nuclear layer and outer nuclear layer, chaos of outer plexiform layer, decreased inner segments of photoreceptor and the loss of outer segments. The novel knock-in mice (RS1-KI) harboring patient-specific mutation will be valuable for development of treatment via genome editing mediated gene correction.

PURPOSE:To quantitate lens nuclear opacity using long-range swept-source optical coherence tomography (SS-OCT) images and to evaluate the correlation of this method to Lens Opacities Classification System III (LOCS III) and a Scheimpflug imaging-based grading system (Pentacam Nuclear Stage function; PNS).METHODS:This study enrolled 120 participants (120 eyes) with age-related nuclear cataracts. The best-corrected visual acuity (BCVA), LOCS III nuclear opalescence (NO) and nuclear colour (NC) were obtained. The nuclear density measured using PNS function (NDPNS) was recorded. Three successive series of long-range SS-OCT images were captured, and the nuclear region was analysed using ImageJ (NIH, Bethesda, Maryland, USA) to generate SS-OCT image-based nuclear density (NDSS-OCT). The repeatability of NDSS-OCT measurement was evaluated using within-subject coefficient of variation (CVw) and intraclass correlation coefficient (ICC). Correlations of NDSS-OCT with NO and NC, BCVA and NDPNS were analysed. According to the integrity of nucleus imaged by Pentacam, patients were divided into two groups, and the parameters were compared between groups.RESULTS:The CVw and ICC for NDSS-OCT measurement were 1.5 % and 0.994, respectively. The NDSS-OCT significantly correlated with NO (r=0.831), NC (r=0.873), BCVA (r=0.655) and NDPNS (r=0.891). The NDSS-OCT, NO and NC, and BCVA were significantly different between the two groups.CONCLUSION:Lens nuclear opacity quantitation using long-range SS-OCT images was repeatable and correlated well with LOCS III and PNS function. The Scheimpflug principle had a limitation in imaging dense nucleus. Long-range SS-OCT seems more promising for objectively and quantitatively assessing lens nuclear opacity.

PURPOSE: To classify retinal neovascularization in untreated early stages of proliferative diabetic retinopathy (PDR) based on optical coherence tomography angiography (OCTA). DESIGN: A cross-sectional study. METHODS: Thirty-five eyes were included. They underwent color fundus photography, fluorescein angiography (FA), and OCTA examinations. Neovascularizations elsewhere (NVEs), neovascularizations at the disc (NVDs), and intraretinal microvascular abnormalities (IRMAs) were scanned by OCTA. The origin and morphology of NVE/NVD/IRMA on OCTA were evaluated. Retinal nonperfusion areas (NPAs) were measured using ImageJ software. RESULTS: In 35 eyes successfully imaged, 75 NVEs, 35 NVDs, and 12 IRMAs were captured. Three proposed subtypes of NVE were identified based on the origins and morphologic features. Type 1 (32 of 75, 42.67%) originated from the venous side, in a treelike shape. Type 2 (30 of 75, 40.00%) originated from capillary networks, with an octopus-like appearance. Type 3 (13 of 75, 17.33%) originated from the IRMAs, having a sea fan shape. NVD originated from the retinal artery, from the retinal vein, or from the choroid, and arose from the bending vessels near the rim of the optic disc. IRMA originated from and drained into retinal venules, extending into the retina. The initial layer and affiliated NPA were significantly different in the 3 subtypes of NVEs (all P<.01). CONCLUSIONS: OCTA allowed identification of the origins and morphologic patterns of neovascularization in PDR. The new classification of retinal neovascularization may be useful to better understand pathophysiological mechanisms and to guide efficient therapeutic strategies. (C) 2018 Elsevier Inc. All rights reserved.

The concept of innate immunity has been expanded to recognize environmental pathogens other than microbial components. However, whether and how the innate immunity is initiated by epithelium in response to environmental physical challenges such as low humidity and high osmolarity in an autoimmune disease, dry eye, is still largely unknown. Using two experimental dry eye models, primary human corneal epithelial cultures exposed to hyperosmolarity and mouse ocular surface facing desiccating stress, we uncovered novel innate immunity pathway by ocular surface epithelium, where oxidized mitochondrial DNA induces imbalanced activation of NLRP3/NLRP6 inflammasomes via stimulation of caspase-8 and BRCC36 in response to environmental stress. Activated NLRP3 with suppressed NLRP6 stimulates caspase-1 activation that leads to IL-1β and IL-18 maturation and secretion. NLRP3-independent caspase-8 noncanonically activates caspase-1 via reciprocal regulation of NLRP3/NLRP6-mediated inflammasomes. Reactive oxygen species-induced mitochondrial DNA oxidative damage and BRCC36 deubiquitinating activity provide a missing link and mechanism by which innate immunity responds to environmental stress via caspase-8-involved NLRP3/NLRP6 inflammasomes.

Purpose To evaluate the long-term outcomes of ciliary sulcus versus capsular bag fixation of intraocular lenses (IOLs) in children after pediatric cataract surgery. Methods IOL was implanted in the ciliary sulcus in 21 eyes of 14 children, and in the capsular bag in 19 eyes of 12 children for the treatment of pediatric cataract in an institutional setting. Ultrasound biomicroscopy (UBM) was performed. Main outcome measures included IOL decentration, IOL tilt, anterior chamber depth (ACD), angle-opening distance at 500 μm (AOD500), trabecular-iris angle (TIA), best-corrected visual acuity (BCVA), intraocular pressure (IOP), and incidence of postoperative complications. Results The mean follow-up period was 6.81 ± 1.82 years. Comparing to the capsular bag fixation group, the ciliary sulcus fixation group had higher vertical IOL decentration, horizontal IOL tilt, and vertical IOL tilt (p = 0.02, 0.01,0.01, respectively), higher incidence of iris-IOL contact and peripheral anterior synechia (p = 0.001, 0.03, respectively), smaller ACD, AOD500, and TIA (p = 0.02, 0.03, 0.04, respectively), higher mean IOP (17.10 ±6.06 mmHg vs.14.15± 4.74 mmHg, p = 0.01), and higher incidence of secondary glaucoma (28.57% vs. 10.53%, p = 0.007).There was no significant difference between the two groups with regard to the BCVA, refractive errors, incidence of myopic shift, nystagmus, strabismus, and visual axis opacity. Conclusions Ciliary sulcus fixation of IOLs in pediatric eyes may increase IOL malposition and crowding of the anterior segment, and may associate with a higher risk of secondary glaucoma compared to capsular bag fixation of IOLs.