Use of an Iris Speculum for Retrolental Membrane Dissection for Stage 5 Prematurity of Retinopathy Complicated With Pupillary Adhesion.

PURPOSE: To report a novel use of an iris speculum to assist with membrane dissection and trough separation for stage 5 retinopathy of prematurity-related funnel-shaped tractional retinal detachment complicated with pupillary adhesion. METHODS: Limbus-based closed vitrectomy and membrane dissection were performed in 10 eyes (9 patients) with stage 5 retinopathy of prematurity-related tractional retinal detachment and pupillary adhesion. After synechiolysis, an iris speculum was positioned to enlarge the pupil for surgical visualization and maintain a neutral iris plane. The retrolental membrane was dissected bimanually and circumferentially along the peripheral trough and then toward the central retina with vertical scissors and end-gripping forceps. RESULTS: In all 10 eyes, retrolental membranes were entirely removed and troughs were circumferentially unraveled. Follow-up examinations performed 6 to 18 months postoperatively showed reattachment of the retina in 3 eyes with an open-narrow funnel and 6 of 7 eyes with a narrow-narrow funnel. A near-circular pupil without recurrent pupillary adhesion was preserved in all nine eyes showing retinal reattachment. CONCLUSION: This use of the iris speculum effectively exposes the surgical field for the entire removal of retrolental tissue and interruption of the peripheral trough in stage 5 retinopathy of prematurity-related tractional retinal detachment complicated with pupillary adhesion. The pupil's configuration is well preserved postoperatively.

Viscodelamination of Localized Retrolental Plaques During Lens-Sparing Vitrectomy in Eyes With Pediatric Tractional Vitreoretinopathy.

PURPOSE: To report viscodelamination of localized retrolental plaques during lens-sparing vitrectomy in eyes with pediatric tractional vitreoretinopathy. METHODS: Viscodelamination of retrolental plaques was performed during 23-gauge lens-sparing vitrectomy in 11 eyes from 11 children with a median age (range) of 12 (4-58) months. There were five eyes with Stage 4 familial exudative vitreoretinopathy, one eye with Stage 4B retinopathy of prematurity, and five eyes with anterior-posterior persistent fetal vasculature syndrome. Retrolental plaques were separated from the posterior lens capsule by the tension of viscoelastic injection in the Berger's space. RESULTS: In 10 of 11 eyes, retrolental plaques were removed from posterior surface of lens without capsular tearing. During the 12-month to 18-month follow-up period, lens clarity along the visual axis was retained in 5 eyes with familial exudative vitreoretinopathy, one eye with retinopathy of prematurity, and 2 of 5 eyes with persistent fetal vasculature. Atraumatic viscodelamination was associated with retrolental plaques that did not incorporate into the posterior lens capsule. Retinal dragging was reversed in all 11 eyes. CONCLUSION: Viscodelamination may be effective for the dissection of retrolental plaques related to pediatric vitreoretinopathy in selected cases.

Intraoperative Perfluorocarbon Liquid Tamponade Technique for Treatment of Extensive Retinal Detachment Secondary to a Myopic Macular Hole.

BACKGROUND/PURPOSE: To report an intraoperative perfluorocarbon liquid (PFCL) tamponade technique in treating extensive retinal detachment secondary to a myopic macular hole (MH) through pars plana vitrectomy. METHODS: The technique was applied in nine eyes with MH-RD extending two quadrants or more areas. The procedures for pars plana vitrectomy included: 1). thorough drainage of subretinal fluid through the MH with fluid-air exchange; 2). PFCL tamponade on the macular area for more than 10 minutes; and 3). repairing the MH after PFCL was removed. RESULTS: All nine eyes gained intraoperative retinal reattachment after PFCL tamponade for 22.22 ± 8.01 minutes and removal of PFCL. Procedures for MH closure included internal limiting membrane peeling in eight eyes, with internal limiting membrane free flap insertion (four eyes), internal limiting membrane inverted flap insertion (two eyes), or lens capsular flap transplantation (three eyes). All eyes received C3F8 tamponade. During 9.11 ± 3.89 months of follow-up, eight of the nine eyes (89%) achieved retinal reattachment and MH closure; one eye achieved anatomical success after reoperations. All eyes had vision improvement at the last follow-up. CONCLUSION: This new technique in pars plana vitrectomy may promote anatomical and functional recovery in the treatment of extensive retinal detachment secondary to a myopic MH.

Modified Trisection Technique: One-Trip Explantation for Foldable Intraocular Lens.

PURPOSE: We present a new technique that allows an intraocular lens to be explanted through the small incisions used in modern cataract surgery. METHODS AND RESULTS: The intraocular lens optic is cut into three connected pieces at the 1-mm-wide end with scissors. Then, with the stabilizing counterforce provided by a pair of vitreoretinal forceps through a paracentesis, the middle piece is removed first, followed by the two side pieces connected with haptics flipped over at the connected part. These two parts overlap each other when passing through the incision, eventually resulting in the explantation of the intraocular lens, as an intact piece. CONCLUSION: We believe this method provides a simple and effective way to remove intraocular lens through very small incisions, which could also reduce complications and hasten patient's recovery.

Competing endogenous RNA network associated with oxygen-induced retinopathy: Expression of the network and identification of the MALAT1/miR-124-3p/EGR1 regulatory axis.

Retinopathy of prematurity (ROP) is a severe retinal dysfunction in prematurely born babies. The relationship between non-coding RNAs and retinopathy of prematurity (ROP) remain unclear. Microarray analysis of lncRNAs, miRNAs, and mRNAs was conducted in a mouse model of ROP. A competing endogenous RNA (ceRNA) network was constructed. The relationship among MALAT1, miR-124-3p, and Early growth response protein 1 (EGR1) was assessed in hypoxia-induced primary human umbilical vein endothelial cells (HUVECs) and ROP mouse model. In the study, we found 2252 lncRNAs, 1239 mRNAs, and 36 miRNAs were differentially regulated. ceRNA network consisting of 21 lncRNAs, 10 miRNAs, and 19 mRNAs was established. Of the most down-regulated miRNAs, miR-124-3p was selected for additional study. miR-124-3p ceased the migration and proliferation of primary HUVECs in hypoxic conditions, and directly suppressed EGR1. Additionally, MALAT1 directly sponged miR-124-3p. Knockdown of MALAT1 decreased EGR1 expression and inhibited the migration and proliferation of primary HUVECs in hypoxia. Furthermore, these changes were rescued by depletion of miR-124-3p. In vivo, intravitreal injection of miR-124-3p, shMALAT1 decreased EGR1 expression and markedly suppressed retinal neovascularization in OIR models. Intravitreal injection of shMALAT1 and miR-124-3p antagomir at the same time can promote retinal neovascularization, which reversed the suppression of retinal neovascularization functioned by shMALAT1. In conclusion, the expression profiles of lncRNAs and miRNAs and the ceRNA network in a mouse model of ROP may be indicative of the underlying mechanisms of retinal angiogenesis and neural activity. The MALAT1/miR-124-3p/EGR1 regulatory axis is partly responsible for retinal neovascularization, which may provide a novel theoretical basis for the pathogenesis of ROP.

Repeated intravitreal ranibizumab for reactivated retinopathy of prematurity after intravitreal ranibizumab monotherapy: vascular development analysis.

PURPOSE: To evaluate the retinal vascularization of repeated intravitreal ranibizumab (IVR) for reactivated retinopathy of prematurity (ROP) treated with IVR monotherapy. METHODS: The retrospective study reviewed ROP infants who accepted IVR injection as the first treatment in our department from January 2017 to December 2018. The ratio of the distance from the center of the optic disc to the border of the vascularized zone (DB) to the distance from the center of the disc to the fovea (DF) was used for the vascular outgrowth analysis. RESULTS: Seventy-eight infants were included in the study. A total of 54.3% of the reactivated ROP patients could achieve complete vascularization after repeated IVR injections. Gestational age (GA) > 29 weeks and a temporal DB/DF ratio ≥ 3 in the first IVR were potential predictors for complete retinal vascularization after IVR monotherapy. The temporal DB/DF ratio ≥ 3.6 in the second IVR injection was a potential predictor for complete retinal vascularization after repeated IVR for ROP reactivation. CONCLUSIONS: Reactivated ROP after IVR monotherapy can be treated successfully with repeated IVR injections. GA and temporal DB/DF ratio are potential predictors of complete retinal vascularization in ROP infants treated with IVR.

CLINICAL FEATURES AND SURGICAL OUTCOMES OF ENCIRCLING SCLERAL BUCKLING WITH CRYOTHERAPY IN FAMILIAL EXUDATIVE VITREORETINOPATHY-ASSOCIATED RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To report the clinical features and surgical outcomes of encircling scleral buckling surgery with cryotherapy in familial exudative vitreoretinopathy (FEVR) patients with rhegmatogenous RD. METHODS: This study was a consecutive, retrospective interventional case series. Clinical features, including the FEVR stage, proliferative vitreoretinopathy grade, range of RD and degeneration, and presence of retinal breaks, and surgical outcomes, including the success rate, best-corrected visual acuity, and myopic shift, were analyzed. RESULTS: There were 16 eyes with Stage 3A FEVR and eight eyes with Stage 4A FEVR. 13 eyes had Grade A proliferative vitreoretinopathy, and 11 eyes had Grade B proliferative vitreoretinopathy. Retinal reattachment was achieved in 22 of 24 eyes (91.67%) with FEVR-rhegmatogenous RD after initial encircling scleral buckling surgery. The best-corrected visual acuity improved from a mean of 1.08 ± 0.86 logarithm of the minimum angle of resolution preoperatively to 0.45 ± 0.41 logarithm of the minimum angle of resolution postoperatively (P < 0.01). A myopic shift of -2.39 ± 1.38 (range, -1 to -6) diopter (P < 0.01) was observed. The mean follow-up period was 34.5 ± 27.7 (range, 7-104) months. CONCLUSION: Our study clarified the efficacy of encircling scleral buckling surgery with cryotherapy in FEVR-rhegmatogenous RD with Stage 3A or 4A FEVR and Grade A or B proliferative vitreoretinopathy, especially in patients with multiple retinal holes.

Secondary glaucoma caused by a special type of persistent fetal vasculature.

PURPOSE: To investigate the clinical features and surgical outcomes in infants with glaucoma secondary to a special anterior-anterior type of persistent fetal vasculature (AAPFV). METHODS: This study retrospectively reviewed the medical records of infants who underwent of the synechialysis, pupilloplasty, with or without lensectomy and limbal vitrectomy due to AAPFV and with at least 6 months of postoperative follow-up. RESULTS: Eleven patients were included. The median age at surgery was 4.0 months (interquartile range: 7 months). The mean follow-up was 21.0 ± 11.3 months. All patients achieved a normal anterior chamber, improved pupillary configuration, and normal intraocular pressure (IOP), except one that developed phthisis bulbi at the last visit. A total of 81.8% (9/11) eyes exhibited improved corneal transparency. Histopathologic findings of four pupillary membranous specimens under light microscopy showed similar components compared with PFV. Two eyes developed postoperative complications, including retinal detachment and hyphema, requiring additional surgeries. Postoperative visual acuity changed from no light perception to light perception in 6/9 patients. CONCLUSIONS: AAPFV is a special type of PFV with a potential for secondary glaucoma. Surgery treatment may offer better vision with improved cosmetic outcomes and a better controlled IOP. TRIAL REGISTRATION: The study was approved by the local institutional review board (IRB) (Approval No. XHEC-D-2021-043, Ethical Committee of Xin Hua Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China).

INTRAVITREAL RANIBIZUMAB TREATMENT FOR ADVANCED FAMILIAL EXUDATIVE VITREORETINOPATHY WITH HIGH VASCULAR ACTIVITY.

PURPOSE: To determine the efficacy of intravitreal ranibizumab (IVR) treatment for advanced familial exudative vitreoretinopathy with high vascular activity. METHODS: The retrospective interventional case series included 28 eyes (20 patients) that had IVR in combination or not with other treatment, for Stage 3 to 5 familial exudative vitreoretinopathy with active fibrovascular proliferation and prominent subretinal exudation. Outcome measures were fundus features after treatment, associated clinical variables, and genetic mutations. RESULTS: The age of patients at the first IVR ranged from 0.2 to 36 months. An average of 1.3 IVR injections per eye were given. Familial exudative vitreoretinopathy regressed in 16 (57%) eyes and progressed in 12 eyes (43%) after IVR. Laser and/or vitrectomy was performed on 13 eyes. The retina was reattached in 22 eyes (78%) after 24 to 58 months follow-up. Clinical variables associated with progression after IVR were preexisting fibrovascular proliferation over one quadrant and persistent vascular activity after the initial injection (P < 0.05). Familial exudative vitreoretinopathy-causative genetic mutations in 11 patients were related to variable response to IVR treatment. CONCLUSION: Intravitreal ranibizumab treatment may effectively regress advanced familial exudative vitreoretinopathy with high vascular activity in selected cases. Different treatment outcomes may be relevant to variable presentation and genetic heterogeneity of familial exudative vitreoretinopathy.

Intraocular lens implantation in combination with lensectomy and vitrectomy for persistent fetal vasculature.

PURPOSE: To present surgical outcomes following intraocular lens (IOL) implantation in combination with lensectomy and vitrectomy for the treatment of persistent fetal vasculature (PFV). METHODS: This interventional case series included 19 eyes from 19 patients with unilateral combined PFV. Limbal lensectomy, capsulotomy, anterior vitrectomy, dissection of the retrolental membrane and stalk, and in-the-bag or in-the-sulcus IOL implantation were performed for the treatment of visually significant lenticular opacity with the presence of a retrolental fibrovascular membrane and stalk, in an eye with sufficient capsular support. Postoperative anatomical and visual outcomes were evaluated. RESULTS: After 22 to 50 months of follow-up, IOLs were well positioned in 18 (95%) of 19 eyes. Retinal dragging was reversed in all 8 eyes with preexisting peripapillary tractional retinopathy. Major complications occurred in 2 eyes (11%): one eye (5.5%) of vitreous hemorrhage and posterior capsular opacity and one eye (5.5%) of IOL dislocation. Nine (47%) of 19 eyes achieved best-corrected visual acuity (BCVA) above 20/200. Myopic shift after IOL implantation ranged from 0.75 to 4.17 D. Compared with eyes with poorer BCVA, eyes with BCVA above 20/200 had a better preoperative BCVA (mean 20/400 vs. 20/4000, P = 0.004) and were less likely to have preexisting peripapillary tractional retinopathies (11% vs. 70%, P = 0.002). CONCLUSION: Primary IOL implantation in combination with lensectomy and vitrectomy is an alternative to treat eyes with combined PFV. Prospects for rehabilitation may be limited by poor preoperative visual function and the presence of tractional retinopathies preoperatively. Postoperative refractive status requires long-term monitoring.

Reduction of circular RNA expression associated with human retinoblastoma.

This study investigated the profile of circular RNA (circRNA) expression and its epigenetic role associated with human retinoblastoma (RB). Twelve paired primary samples from un-treated RB patients (primary RB samples and corresponding adjacent normal retinal samples) and eight recurrent RB samples from RB patients having recurrence after treatment were collected. Ribosomal-RNA depleted sequencing was performed in four paired primary samples. Quantitative polymerase chain reaction was conducted to validate circRNA and mRNA expression in the other eight paired primary samples and in eight recurrent RB samples. Bioinformatic analysis was applied to predict the oncological signal pathways and the binding microRNA (miRNA) of circRNA. As a result, a total of 47640 circRNAs were identified by RNA-sequencing, with a lower abundance of circRNAs in primary RB samples relative to matched normal retinal samples [22366 (47%) versus 37161 (78%), P <0.001]. Among the 11887 overlapping circRNAs in both RB and normal retinal samples, 550 circRNAs were downregulated and seven were upregulated in primary RB samples compared to normal retinal samples. The host genes of the differentially expressed circRNAs were associated with chromatin modification. TET1-has_circ_0093996 (ten-eleven translocation-1), whose host gene TET1 participates in chromatin modifying, was downregulated in both primary and recurrent RB samples. Programmed cell death 4 （PDCD4) was also downregulated in both primary and recurrent RB samples. We used bioinformatic tools to construct a complete regulatory axis including TET1-has_circ_0093996-miR-183-PDCD4 that regulates RB pathogenesis. In conclusion, circRNA expression is downregulated in RB tumor, which suggests epigenetic regulation of RB pathogenesis by circRNAs.

Diagnosis of complicated FEVR preoperatively and intra-/post-operatively: characteristics and risk factors for diagnostic timing.

BACKGROUND: To delineate the characteristics of complicated familial exudative vitreoretinopathy (FEVR) patients diagnosed before surgery or intra-/post-operatively and to analyze the risk factors for the diagnostic timing. METHODS: Forty-eight patients who underwent surgery and were diagnosed as FEVR in our department were retrospectively reviewed. Data were collected including the demographic and clinical characteristics of these patients. FEVR patients were divided into 2 groups according to the diagnostic timing: FEVR diagnosed pre-operatively (23 patients), FEVR diagnosed intra-/post-operatively (25 patients). Multivariable analysis was applied for analyzing the risk factors for diagnostic timing. RESULTS: The clinical characteristics of the FEVR patients were of great variability, including retinal detachment (RD), disappear of anterior chamber, retrolental membrane, epiretinal membrane (ERM), vitreous hemorrhage (VH), myopic foveoschisis (MF), lamellar macular hole (LMH), high myopia (HM). And the referral diagnosis or pre-operative diagnosis were always non-specific. The majority of the referral or preoperative diagnosis were unilateral RD (52.1%), bilateral RD (8.3%), unilateral persistent fetal vasculature (PFV) (8.3%), bilateral PFV (4.2%). There are two risk factors for the complicated FEVR cases diagnosed as FEVR preoperatively: pre-operative ocular manifestations with RD only (OR, 0.104; p-value, 0.022), positive parent's fluorescein angiography (FA) (OR, 0.105; p-value, 0.035). CONCLUSIONS: The phenotypes of FEVR were greatly variable, they can mimic many non-specific vitreoretinal disorders. The most non-specific referral diagnosis/pre-operative diagnosis was unilateral RD, bilateral RD, unilateral PFV, bilateral PFV. A positive family history or a simple ocular presentation with RD only could contribute to diagnose FEVR preoperatively.

Ranibizumab injection and laser photocoagulation to treat type 1 retinopathy of prematurity after 40 weeks post menstrual age: a retrospective case series study.

BACKGROUND: Type 1 retinopathy of prematurity (ROP) is occasionally observed in preterm infants after the postmenstrual age (PMA) of 40 weeks; however, evidence-based treatment guidelines are largely lacking. In this study, we report the clinical characteristics of preterm infants with type 1 ROP at PMA of > 40 weeks and compare the treatment outcomes of intravitreal ranibizumab (IVR) and laser therapy. METHODS: Twenty-seven eyes of 14 infants, primarily treated for type 1 ROP after 40 weeks PMA by IVR (17 eyes in 9 infants) or by laser photocoagulation (10 eyes in 5 infants) were included in this retrospective analysis. The preoperative fundus characteristics and the structural outcomes and additional treatment after 6 months were analyzed. RESULTS: Of the 27 eyes, 20 eyes (74%) had zone II stage 3 plus disease (+) ROP and 7 eyes had zone II stage 2 + ROP. Seventeen (63%) eyes showed thick fibrous ridges. After primary treatment at 40-48 weeks PMA, ROP regression was observed in a similar proportion of eyes in the IVR and laser groups (88% vs. 70%; p = 0.326); complete vascularization was observed in 24% eyes in the IVR group. Compared to laser group, a higher proportion of eyes in IVR group received additional treatment (IVR group 76% vs. laser group 30%; p = 0.040), for unresolved peripheral avascularity in 11 eyes and ROP progression with fibrotic contraction in 2 eyes after primary IVR. CONCLUSION: Preterm infants with type 1 ROP at > 40 weeks PMA displayed enhanced fibrotic proliferation. Both primary IVR and laser effectively promote ROP regression. Primary IVR cannot guarantee full retinal vascularization but is associated with a risk of fibrotic contraction.

Aqueous cytokine levels associated with severity of type 1 retinopathy of prematurity and treatment response to ranibizumab.

PURPOSE: To determine the aqueous humor levels of cytokines in eyes with type 1 retinopathy of prematurity (ROP) before primary intravitreal injection of ranibizumab (IVR). METHODS: Forty-nine infants with type 1 ROP (56 eyes of 28 infants in the threshold ROP group and 42 eyes of 21 infants in the type 1 pre-threshold ROP group) received primary IVR and 49 aqueous humor samples were obtained preoperatively. Aqueous humor samples from 15 infants (15 eyes) undergoing congenital cataract surgery were used as controls. The concentrations of 27 cytokines were measured by a multiplex bead assay. Infants with persistent, recurrent, or progressive ROP after IVR were retreated. RESULTS: The preoperative aqueous levels of 16 cytokines were significantly different among type 1 pre-threshold, threshold ROP, and control groups (P < 0.05). The concentrations of vascular endothelial growth factor (VEGF) (P < 0.001), interferon-γ (P < 0.001), interleukin (IL)-10 (P < 0.001), and IL-12 (P < 0.001) were the highest in the threshold ROP group, less in the type 1 pre-threshold ROP group, and the lowest in the control group. Retreatment was given to 55% of infants with ROP within a 48-week follow-up period after primary IVR. Higher VEGF (hazard ratio [HR] = 1.001, P = 0.001) and macrophage inflammatory protein-1ß (HR = 1.085, P = 0.022) levels were independently correlated with ROP retreatment. CONCLUSIONS: Higher aqueous levels of VEGF and inflammatory cytokines were associated with more severe type 1 ROP and ROP retreatment after primary IVR.

Ranibizumab Injection as Primary Treatment in Patients with Retinopathy of Prematurity: Anatomic Outcomes and Influencing Factors.

PURPOSE: To investigate the anatomic outcomes and influencing factors of ranibizumab in the treatment of retinopathy of prematurity (ROP). DESIGN: Retrospective case series. PARTICIPANTS: A total of 283 eyes of 145 patients with type 1 ROP treated with intravitreal injection of ranibizumab (IVR) as primary treatment. METHODS: Retrospective review of infants who were diagnosed with type 1 ROP and accepted IVR (0.25 mg/0.025 ml) as primary treatment from January 2012 to August 2015. The anatomic outcomes and the influencing factors were analyzed. MAIN OUTCOME MEASURES: Anatomic outcomes of ROP eyes after IVR and the influencing factors. RESULTS: A total of 283 eyes of 145 patients were included in this study. There were a total of 266 eyes (94.0%) in the positive response group and 17 eyes (6.0%) in the negative/no response group after IVR. Within the positive response group, 139 eyes (48.6%) were in the regression without reactivation subgroup, and 127 eyes (44.9%) were in the regression with reactivation subgroup. A total of 152 eyes received additional laser or surgical treatment. At the last visit, 278 eyes (98.2%) had attached retinas, and 5 eyes (1.8%) had retinal detachment. A classification tree model showed that for patients with gestational age (GA) ≤29.5 weeks, the possibility of experiencing reactivation after IVR is higher than that of those with GA >29.5 weeks (61.6% vs. 29.6%). Moreover, for patients with GA ≤29.5 weeks, those diagnosed with zone II stage 2+ ROP have a lower possibility of experiencing reactivation than other patients (37.9% vs. 80%). CONCLUSIONS: Intravitreal injection of ranibizumab seemed to be effective in treating patients with ROP. After treatment, there were primarily 3 different outcomes. Our predictive tree model is helpful for ophthalmologists to evaluate the risk of reactivation.

Ultra-wide-field scanning laser ophthalmoscopy assists in the clinical detection and evaluation of asymptomatic early-stage familial exudative vitreoretinopathy.

PURPOSE: This study aims to investigate the ability of the ultra-wide-field scanning laser ophthalmoscope (UWF SLO) in clinically detecting and evaluating asymptomatic early-stage familial exudative vitreoretinopathy (FEVR). METHODS: We retrospectively reviewed 163 eyes of 83 asymptomatic family members of 48 patients with FEVR. UWF SLO imaging (Optos® PLC, Scotland, UK) was performed on asymptomatic family members as a preliminary screening test for fundus anomalies, and the findings were compared with subsequent examinations using indirect fundus ophthalmoscopy in full mydriasis, fluorescein angiography (FA), fundus autoflourescence, and genetic sequencing. RESULTS: A total of 86 eyes of 43 asymptomatic family members were clinically diagnosed with early-stage FEVR, and 17 of the affected 43 family members were also genetically diagnosed. Compared with FA as a standard, the UWF SLO was highly effective in diagnosing FEVR with a sensitivity and specificity of 93.0 % and 97.5 %, respectively. The UWF SLO was able to diagnose early-stage FEVR in 93.0 % of eyes, and guided the selection of therapies in 46.5 % of the eyes studied. CONCLUSION: UWF SLO is a valuable imaging tool for detecting fundus anomalies related to early-stage FEVR, and this tool can assist in the clinical diagnosis and evaluation of early-stage FEVR in asymptomatic family members of patients with FEVR.

New insight in treating autoimmune diseases by targeting autophagy.

Autophagy is a highly conserved biological process in eukaryotes, which degrades cellular misfolded proteins, damaged organelles and invasive pathogens in the lysosome-dependent manner. Autoimmune diseases caused by genetic elements, environments and aberrant immune responses severely impact patients' living quality and even threaten life. Recently, numerous studies have reported autophagy can regulate immune responses, and play an important role in autoimmune diseases. In this review, we summarised the features of autophagy and autophagy-related genes, enumerated some autophagy-related genes involved in autoimmune diseases, and further overviewed how to treat autoimmune diseases through targeting autophagy. Finally, we outlooked the prospect of relieving and curing autoimmune diseases by targeting autophagy pathway.

CSNK1A1/CK1α suppresses autoimmunity by restraining the CGAS-STING1 signaling.

STING1 (stimulator of interferon response cGAMP interactor 1) is the quintessential protein in the CGAS-STING1 signaling pathway, crucial for the induction of type I IFN (interferon) production and eliciting innate immunity. Nevertheless, the overactivation or sustained activation of STING1 has been closely associated with the onset of autoimmune disorders. Notably, the majority of these disorders manifest as an upregulated expression of type I interferons and IFN-stimulated genes (ISGs). Hence, strict regulation of STING1 activity is paramount to preserve immune homeostasis. Here, we reported that CSNK1A1/CK1α, a serine/threonine protein kinase, was essential to prevent the overactivation of STING1-mediated type I IFN signaling through autophagic degradation of STING1. Mechanistically, CSNK1A1 interacted with STING1 upon the CGAS-STING1 pathway activation and promoted STING1 autophagic degradation by enhancing the phosphorylation of SQSTM1/p62 at serine 351 (serine 349 in human), which was critical for SQSTM1-mediated STING1 autophagic degradation. Consistently, SSTC3, a selective CSNK1A1 agonist, significantly attenuated the response of the CGAS-STING1 signaling by promoting STING1 autophagic degradation. Importantly, pharmacological activation of CSNK1A1 using SSTC3 markedly repressed the systemic autoinflammatory responses in the trex1-/- mouse autoimmune disease model and effectively suppressed the production of IFNs and ISGs in the PBMCs of SLE patients. Taken together, our study reveals a novel regulatory role of CSNK1A1 in the autophagic degradation of STING1 to maintain immune homeostasis. Manipulating CSNK1A1 through SSTC3 might be a potential therapeutic strategy for alleviating STING1-mediated aberrant type I IFNs in autoimmune diseases.Abbreviations: BMDMs: bone marrow-derived macrophages; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; HTDNA: herring testes DNA; IFIT1: interferon induced protein with tetratricopeptide repeats 1; IFNA4: interferon alpha 4; IFNB: interferon beta; IRF3: interferon regulatory factor 3; ISD: interferon stimulatory DNA; ISGs: IFN-stimulated genes; MEFs: mouse embryonic fibroblasts; PBMCs: peripheral blood mononuclear cells; RSAD2: radical S-adenosyl methionine domain containing 2; SLE: systemic lupus erythematosus; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1.

Overexpression of TRPV1 activates autophagy in human lens epithelial cells under hyperosmotic stress through Ca2+-dependent AMPK/mTOR pathway.

AIM: To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells (LECs) under hyperosmotic stress. METHODS: LECs were treated with hyperosmotic stress at the concentration of 270, 300, 400, 500, or 600 mOsm for 6, 12, 18, 24h in vitro. Polymerase chain reaction (PCR) was employed for the mRNA expression of autophagy-related genes, while Western blotting detected the targeted protein expression. The transfection of stub-RFP-sens-GFP-LC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux. Scanning electron microscopy was used to detect the existence of autolysosome. Short interfering RNA of autophagy-related gene (ATG) 7, transient receptor potential vanilloid (TRPV) 1 overexpression plasmid, related agonists and inhibitors were employed to their influence on autophagy related pathway. Flow cytometry was employed to test the apoptosis and intracellular Ca2+ level. Mitochondrial membrane potential was measured by JC-1 staining. The cell counting kit-8 assay was used to calculate the cellular viability. The wound healing assay was used to evaluate the wound closure rate. GraphPad 6.0 software was utilized to evaluate the data. RESULTS: The hyperosmotic stress activated autophagy in a pressure- and time-dependent manner in LECs. Beclin 1 protein expression and conversion of LC3B II to LC3B I increased, whereas sequestosome-1 (SQSTM1) protein expression decreased. Transient Ca2+ influx was stimulated caused by hyperosmotic stress, levels of mammalian target of rapamycin (mTOR) phosphorylation decreased, and the level of AMP-activated protein kinase (AMPK) phosphorylation increased in the early stage. Based on this evidence, autophagy activation through the Ca2+-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress. Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased. Inhibition of autophagy by ATG7 knockdown had similar results. TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress. CONCLUSION: A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.

Clinical observation of a modified technique for intrascleral fixation of flanged three-piece foldable intraocular lenses through a Hoffman pocket.

Purpose: To present the outcomes of a new technique for intrascleral fixation of a flanged three-piece foldable intraocular lens (IOL) without a conjunctival incision. Materials and methods: We retrospectively reviewed a consecutive series of 12 eyes of 12 patients who underwent scleral IOL fixation using this technique. Results: The follow-up period ranged 3-12 months. There was a significant improvement in best-corrected visual acuity, from 0.8 (1.6) logarithm of the minimum angle of resolution (logMAR) preoperatively to 0.45 (0.8) logMAR at the final postoperative follow-up (p = 0.012). Notable complications included one case of pupillary IOL capture and increased intraocular pressure. Conclusion: Our novel technique is a viable solution for managing secondary IOL fixation, enabling the use of a wider variety of IOLs and simplifying the reposition process for dislocated three-piece IOLs. This approach has the potential to lower complication rates and enhance patients' recovery.