Pars plana vitrectomy for retinal detachment using perfluoro-n-octane as intraoperative tamponade:a multicenter,randomized,non-inferiority trial

AIM:To evaluate the efficacy and safety of perfluoro-n-octane(PFO)for ophthalmic surgery versus F-Octane as an intraoperative tamponade in pars plana vitrectomy(PPV)in management of retinal detachment.METHODS:This multicenter,prospective,randomized,double-masked,parallel-controlled,non-inferiority trial was conducted in three ophthalmology clinical centers in China.Patients with retinal detachment,who were eligible for PPV were consecutively enrolled.Participants were assigned to PFO for ophthalmic surgery or F-Octane for intraocular tamponade in a 1:1 ratio.Best-corrected visual acuity(BCVA),intraocular pressure(IOP)measurement,and dilated fundus examination were performed preoperatively and at 1,7±1,28±3d postoperatively.The primary outcome was complete retinal reattachment rate at postoperative day one.The non-inferiority margin was set at 9.8%.The secondary outcomes included intraoperative retinal reattachment rate,and mean changes in IOP and BCVA from baseline to 1,7±1,28±3d postoperatively,respectively.Safety analyses were presented for all randomly assigned participates in this study.RESULTS:Totally 124 eligible patients completed the study between Mar.14,2016 and Jun.7,2017.Sixty of them were randomly assigned to the PFO for ophthalmic surgery group,and 64 were assigned to the F-Octane group.Baseline characteristics were comparable between the two groups.Both groups achieved 100%retinal reattachment at postoperative day one(difference 0,95%CI:-6.21%to 5.75%,P=1).The pre-defined noninferiority criterion was met.No significant difference was observed in intraoperative retinal reattachment rate(difference 1.77%,P=0.61),mean changes in IOP(difference 0.36,-0.09,2.22 mm Hg at 1,7±1,28±3d postoperatively,with all P>0.05)and BCVA(difference 0.04,-0.02,0.06 logMAR at 1,7±1,28±3d postoperatively,all P>0.05)between the two groups.No apparent adverse events related to the utilization of PFO were reported.CONCLUSION:In patients with retinal detachment undergoing PPV,PFO for ophthalmic surgery is non-inferior to F-Octane as an intraocular tamponade,and both are safe and well-tolerated.

Non-contact wide-field viewing system-assisted scleral buckling surgery for retinal detachment in silicone oilfilled eyes

AIM:To evaluate scleral buckling(SB)surgery using a noncontact wide-field viewing system and 23-gauge intraocular illumination for the treatment of rhegmatogenous retinal detachment in silicone oil(SO)-filled eyes.METHODS:Totally 9 patients(9 eyes)with retinal detachment in SO-filled eyes were retrospectively analyzed.All patients underwent non-contact wide-field viewing system-assisted buckling surgery with 23-gauge intraocular illumination.SO was removed at an appropriate time based on recovery.The patients were followed up for at least 3mo after SO removal.Retinal reattachment,complications,visual acuity and intraocular pressure(IOP)before and after surgery were observed.RESULTS:Patients were followed up for a mean of 8.22mo(3-22mo)after SO removal.All patients had retinal reattachment.At the final follow-up,visual acuity showed improvement for 8 patients,and no change for 1 patient.The IOP was high in 3 patients before surgery,but it stabilized after treatment;it was not affected in the other patients.None of the patients had infections,hemorrhage,anterior ischemia,or any other complication.CONCLUSION:This new non-contact wide-field viewing system-assisted SB surgery with 23-gauge intraocular illumination is effective and safe for retinal detachment in SO-filled eyes.

Efficacy of scleral buckling for the treatment of rhegmatogenous retinal detachment using a novel foldable capsular buckle

●AIM:To evaluate the effectiveness and safety of scleral buckling for the treatment of rhegmatogenous retinal detachment(RRD)using a novel foldable capsular buckle(FCB).●METHODS:This was a series of case observation studies.Eighteen patients(18 eyes)who visited our ophthalmology department between August 2020 and August 2022 and were treated for RRD with scleral buckling using FCB were included.The procedure was similar to conventional scleral buckling,while a balloon-like FCB was placed onto the retinal break with balanced salt solution filling for a broad,external indentation instead of the silicone buckle.The retinal reattachment rate,best corrected visual acuity(BCVA),intraocular pressure(IOP),refractive dioptre and astigmatism degree,and complications were evaluated and recorded.●RESULTS:There were 7 males and 11 females aged 19-58y.The average time course of RRD was 12d,ranging from 7-20d.The retinal break was located in the superior quadrants in 8 eyes and in the inferior quadrants in 10 eyes,with macula-off detachments in 12 eyes.The patients were followed-up for at least 6mo.The final retinal reattachment rate was 100%.The BCVA was significantly improved compared with the baseline(P<0.05).There was no significant change in refractive dioptre or astigmatism degree at each follow-up(all P>0.05).Three patients had transiently high IOPs within one week after surgery.Mild diplopia occurred in 5 patients after surgery and then disappeared after the balloon fluid was removed.●CONCLUSION:The success rate of FCB scleral buckling for RRD is satisfactory.This procedure can be expected to be applied in new,uncomplicated cases of RRD.

Rhegmatogenous retinal detachment in highly myopic eyes with implantable collamer lens

AIM:To investigate the clinical characteristics,treatment methods and outcomes of rhegmatogenous retinal detachment(RRD)in highly myopic eyes with implantable collamer lens(ICL).METHODS:High myopia patients who received treatment for nontraumatic RRD after ICL implantation surgery at the Retinal Department of Zhongshan Ophthalmic Center from Jan 2018 to Dec 2022 were reviewed.Comprehensive ophthalmologic examinations including visual acuity measurement and digital fundus photography were performed in each patient.RESULTS:A total of nine RRD eyes from nine patients who received V4c-ICL implantation were included.The mean time from ICL implantation surgery to the diagnosis of RRD was 32.44±22.56mo(range,1-60mo).At the initial visit for RRD,giant retinal tear(GRT),horseshoe tear,simple round hole,and horseshoe tear combined with round hole were detected in 3,3,2,and 1 eye(s),respectively,with maculaoff in eyes.Eight patients received surgical treatment,and one patient was treated by retinal laser photocoagulation alone.The ICL was preserved in 7 eyes.At the last followup,the mean best corrected visual acuity(BCVA)improved significantly from 1.76±1.06 logMAR at presentation to 0.81±1.01 logMAR(P=0.035),and no case of recurrent retinal detachment was found.CONCLUSION:The morphological presentation of retinal breaks is diverse in this study.The ICL can be preserved in most cases during the course of retinal detachment repair surgery in our data,companied with acceptable visual and anatomical outcomes.

Postnatal development of rat retina:a continuous observation and comparison between the organotypic retinal explant model and in vivo development

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.

Müller cells are activated in response to retinal outer nuclear layer degeneration in rats subjected to simulated weightlessness conditions

A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.

Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis

Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.

Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy

Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.

Vitrectomy, lensectomy and silicone oil tamponade in the management of retinal detachment associated with choroidal detachment

AIM: To report the results of combined vitrectomy, lensectomy and silicone oil (SO) tamponade in treating primary rhegmatogenous retinal detachment (RRD) associated with choroidal detachment (CD). · METHODS: A retrospective, consecutive and case series study of 21 subjects with concurrent RRD associated with CD was conducted. All subjects underwent a standard three -port 20G pars plana vitrectomy (PPV) with lensectomy and silicone oil tamponade. Mean follow -up time was 8 months (rang from 4 to 19 months). The primary and final anatomic success rate, visual acuity and final intraocular pressure (IOP) were recorded and analyzed. ·RESULTS: Of 21 subjects, 8 were women and 13 were men. Age at presentation ranged from 22 to 75 years (mean 57.4 years). The presenting vision ranged from light perception to 0.15. The initial IOP ranged from 3mmHg to 12mmHg (mean 6.2mmHg). All eyes were phakic except one pseudophakic. No intraocular lens was implanted during the primary surgical intervention. Fifteen of 21 (71.4%) eyes had retina reattached after one operation. Six eyes had recurrent inferior retinal detachment due to proliferation. Five of them were successfully reattached after one or more additional operations. Mean IOP at final follow -up was 15.2mmHg (range from 8mmHg to 20mmHg). One case declined for further operation. The final reattachment rate was 95.2%. Visual acuity improved in 19 (90.5%) eyes, was unchanged in 1 (4.8%) eye and decreased in 1 (4.8%) eye.·CONCLUSION: Combination of vitrectomy, lensectomy and silicone tamponade is an effective method in treating RRD associated with CD, reducing the incidence of postoperative hypotony.

Risk factors of rhegmatogenous retinal detachment associated with choroidal detachment in Chinese patients

AIM： To comprehensively analyze the risk factors of rhegmatogenous retinal detachment （RRD） associated with choroidal detachment （CD）. METHODS： A total of 265 eyes of 265 consecutive cases of RRD were retrospectively analyzed. All patients had systemic and ophthalmologic examination. CD was diagnosed by indirect ophthalmoscopy, B -scan ultrasonography, and ultrasound biomicroscope （UBM）. Each parameter was compared between patients of RRD and rhegmatogenous retinal detachment associated with choroidal detachment （RRDCD）. Logistic regression analysis was used to determine the independent risk factors of CD. RESULTS： There were 52 eyes （19.62%） with CD. Pseudophakia was more commonly seen in RRDCD （21.15% ys6.10%, P=0.002）. Intraocular pressure （lOP） was lower （8.60 ±3.62 ys 12.96 ±3.55, P 〈0.001）, best - corrected visual acuity was worse [3.00 （2.00 to 3.00） vs 1.92 （1.22 to 3.00）, P=-0.001], and refractive error was more myopic [-4 （-9 to -2） vs -2 （-6 to 0）, P=0.007] in RRDCD. Eyes with RRDCD had larger extent of retinal detachment （P=0.007）. In RRDCD, 34.62% of eyes presented with multiple holes （P=0.044） and 25.00% with macular holes （P=0.012）, compared with 20.66% and 14.08% in R RD. High myopia （P=0.039）, low lOP （P=0.017）, and larger extent of retinal detachment （P〈0.001） were significant and independent risk factors for developing CD. - CONCLUSION： For CD in RRD, related factors include BCVA, lOP, lens status, refractive error, extent of retinal detachment, number of holes, and macular hole. Larger extent of retinal detachment, high myopia, and low lOP are significant and independent risk factors.

Comparison of persistent submacular fluid in different preoperative macular status after vitrectomy for rhegmatogenous retinal detachment

AIM： To compare the incidence of persistent submacular fluid（SMF） and visual outcome after pars plana vitrectomy（PPV） for rhegmatogenous retinal detachment（RRD） in different preoperative macular status according to optical coherence tomography（OCT）.METHODS： A non-randomized, retrospective review was performed for patients who underwent successful PPV for RRD. OCT exams were taken preoperatively and 1 mo after surgery, until SMF disappeared. According to the preoperative macular status on OCT, patients were divided into two groups： macula-off RRD（Group A） and maculaon RRD（Group B）. In Group A, there were two subgroups： macula partly detached（Group A1） and macula totally detached（Group A2）. The main outcome measures were the presence of SMF on OCT 1 mo after surgery, and the preoperative and postoperative best corrected visual acuities（BCVA）, among the different groups and depending on the presence or absence of persistent SMF.RESULTS： A total of 139 eyes of 139 patients were included in the study. Persistent SMF at 1 mo after surgery was 15.8%（22/139）, all occurring in Group A（22/101）; Group B had no SMF at 1 mo after surgery（0/38, P=0.002）. The incidence of persistent SMF at 1 mo after surgery in Group A1 was 50%（14/28）, and in Group A2 was 11.0%（8/73, P〈0.001）. Significant differences were shown between the presence and absence of persistent SMF on foveolaoff RRD, the preoperative BCVA, the 1 mo postoperative BCVA, and the degree of the BCVA improvement from 1 mo postoperatively to the final follow-up（P〈0.05）. However, there were no significant differences in the final BCVA（P〉0.05）.CONCLUSION： Persistent SMF after PPV for retinal detachment is associated with preoperative macular status. Macula-uninvolving RRD shows no persistent SMF after PPV. Macular partly detached RRD has a higher incidence of SMF than macula totally detached RRD after PPV. The persistence of SMF may be responsible for the delayed visual recovery, whereas there were no significant differences in the final visual acuity.

Non-buckled vitrectomy for retinal detachment with inferior breaks and proliferative vitreoretinophathy

AIM: To investigate the efficacy of non-buckled vitrectomy with classical endotamponade agents in the treatment of primary retinal detachment (RD) complicated by inferior breaks and proliferative vitreoretinophathy (PVR). METHODS: A retrospective, consecutive and case series study of 40 patients with inferior break RD and PVR >= C1 was conducted. All patients underwent a standard 3-port 20-gauge pars plana vitrectomy (PPV) with gas or silicone oil tamponade without supplementary scleral buckling. The vitreous and all proliferative membrane were completely removed, and retinectomy was performed when necessary. The mean follow-up was 12.5 months. The primary and final anatomic success rate, visual acuity and complications were recorded and analyzed. RESULTS: Primary anatomic success rate was achieved in 35 of 40 eyes (87.5%) and the final anatomic success rate was 100%. The most common cause of redetachment was recurrent PVR. The best-corrected visual acuity (BCVA) at final follow-up was improved in 34 eyes (85%), remained stable in 1 eye (2.5%), and worsened in 5 eyes (12.5%). The mean visual acuity at final follow-up was improved significantly (P=0.000). CONCLUSION: This retrospective study provides evidence that vitrectomy without scleral buckling seemed to be an effective treatment for inferior break RD with PVR. With complete removal of vitreous and proliferative membranes and timing of retinectomy, the inferior breaks which complicated with PVR could be dosed successfully without additional sclera! buckling.

Anatomical and functional outcomes after Densiron 68 heavy silicone oil tamponade for complicated retinal detachment in Chinese eyes

AIM:To evaluate the safety and efficacy of Densiron 68 heavy silicone oil (HSO) tamponade for complicated retinal detachment(RD)in Chinese eyes.METHODS:Twenty-one eyes of 21 patients with complicated RD were included in this retrospective study.All patients underwent pars plana vitrectomy with an internal tamponade using Densiron 68 HSO.Anatomical and functional results and complications were evaluated,including retinal status,visual acuity(VA),intraocular pressure(IOP),intraocular inflammation,lens opacity,and HSO emulsification.RESULTS:Allthepatients were followed up for 3mo to1y(5.8±1.16mo).Retinal reattachment was achieved in 19of 21 patients(90.5%).VA improved in 18 of 21 patients(85.7%),from 1.93 logMAR(±0.48)to 1.52 logMAR(±0.45)(P=0.001).Postoperative complications included early dispersion of HSO in 7 eyes(38.8%),cataract in 10 of 18phakic eyes(55.5%),moderate postoperative inflammation reaction in 10 eyes(47.6%),and elevated IOP in 5 eyes(23.8%),all of which were controlled by medication or by surgery.CONCLUSION:Highanatomical and functional success rates can be achieved with primary vitrectomy for complicated RD by using Densiron 68 HSO;however,it should not be ignored that Densiron 68 HSO can cause some complications in the eye.

Surgical outcomes in inferior recurrences of rhegmatogenous retinal detachment

AIM:To analyze the anatomical and functional outcomes in the inferior recurrences of rhegmatogenous retinal detachment(RRD)depending on the surgical approach.METHODS:Eighty-one eyes of 81 patients(47 males and 34 females with a mean age of 54.8±14.1y)who demonstrated at least one inferior recurrence of RRD were included in this retrospective study.All patients were categorized as having received either circular scleral buckling(SB),pars plana vitrectomy(PPV),a combination of SB and PPV(SB+PPV),PPV with retinotomy(PPV+RT),or PPV+RT and short-term postoperative perfluorocarbon liquid tamponade(PPV+RT+pPFCL).All cases were followed up until successful retinal reattachment or third recurrence.The primary outcome measures were the achievement of the surgical goal without recurrence of RRD and bestcorrected visual acuity(BCVA).RESULTS:After the treatment of the first recurrence,the recurrence rate in the PPV+SB group was statistically significantly lower than that of the PPV(P=0.0012),PPV+RT(P=0.028),or PPV+RT+pPFCL(P=0.047)group.There was no statistically significant difference between PPV+SB,PPV+RT,and PPV+RT+pPFCL groups in the recurrence rate after treatment of the second recurrence(42 eyes).However,there was a statistically significant(P=0.016)trend towards a decrease of recurrence rate after PPV+RT+pPFCL.There was no statistically significant improvement of BCVA in either study group(P>0.05)after both first and second recurrence surgery.The mean time follow-up was 109.0±91.0d before the first recurrence and 210.0±186.6d between previous surgery at second recurrence.CONCLUSION:Patients with first inferior recurrence of RRD may benefit from SB as an adjunct to PPV.RT and short-term pPFCL tamponade in the second recurrence may allow better anatomical outcomes,however,without functional improvement.

Activation of autophagy in photoreceptor necroptosis after experimental retinal detachment

AIM:To investigate whether photoreceptor necroptosis induced by z-VAD-FMK(pan caspase inhibitor) was involved the activation of autophagy and whether Necrostatin-1, a specific necroptosis inhibitor, could inhibit this induction of autophagy after experimental retinal detachment.METHODS:Experimental retinal detachment models were created in Sprague-Dawley rats by subretinal injection of sodium hyaluronate and subretinal injections of z-VAD-FMK, vehicle or z-VAD-FMK plus Necrostatin-1.Three days after retinal detachment, morphologic changes were observed by transmission electron microscopy. In other animals, retinas were subjected to immunoprecipitation and Western Blotting, then probed with anti-RIP1, phosphoserine, LC-3II or caspase 8antibody.RESULTS:It was proved by immunoprecipitation and western blotting, that photoreceptor necroptosis was mediated by caspase-8 inhibition and receptor interacting protein kinase(RIP1) phosphorylation activation. Transmission electron microscope and western blotting results indicated that photoreceptornecroptosis was involved the LC-3II and autophagosomes induction. We also discovered Necrostatin-1 could inhibit RIP1 phosphorylation and LC-3II induction.CONCLUSION:These data firstly indicate photoreceptor necroptosis is associated with the activation of autophagy. Necrostatin-1 protects photoreceptors from necroptosis and autophagy by down-regulation of RIP1 phosphorylation and LC-3II.

Reliability of the ocular trauma score for the predictability of traumatic and post-traumatic retinal detachment after open globe injury

AIM: To elucidate the question of whether the ocular trauma score(OTS) and the zones of injury could be used as a predictive model of traumatic and post traumatic retinal detachment(RD) in patients with open globe injury(OGI).METHODS: A retrospective observational chart analysis of OGI patients was performed. The collected variables consisted of age, date, gender, time of injury, time until repair, mechanism of injury, zone of injury, injury associated vitreous hemorrhage, trauma associated RD, post traumatic RD, aphakia at injury, periocular trauma and OTS in cases of OGI. RESULTS: Totally 102 patients with traumatic OGI with a minimum of 12 mo follow-up and a median age at of 48.6 y(range: 3-104 y) were identified. Final best corrected visual acuity(BCVA) was independent from the time of repair, yet a statistically significant difference was present between the final BCVA and the zone of injury. Severe trauma presenting with an OTS score Ⅰ(P<0.0001) or Ⅱ(P<0.0001) revealed a significantly worse BCVA at last follow up when compared to the cohort with an OTS score >Ⅲ. OGI associated RD was observed in 36/102 patients(35.3%), whereas post traumatic RD(defined as RD following 14 d after OGI) occurred in 37 patients(36.3%). OGI associated RD did not correlate with the OTS and the zone of injury(P=0.193), yet post traumatic RD correlated significantly with zone Ⅲ injuries(P=0.013). CONCLUSION: The study shows a significant association between lower OTS score and zone Ⅲ injury with lower final BCVA and a higher number of surgeries, but only zone Ⅲ could be significantly associated with a higher rate of RD.

Natural history of persistent subretinal fluid following the successful repair of rhegmatogenous retinal detachment

AIM:To provide a detailed description of the natural history of persistent subretinal fluid(SRF)after successful repair of rhegmatogenous retinal detachment(RRD)and its association with visual outcome.METHODS:This was a prospective long-term follow-up for eyes undergoing scleral buckling(SB)surgery for maculaoff RRD.Examinations were carried out preoperatively and postoperatively at 1,3,6,9 and 12 mo,until persistent SRF had completely resolved.One month postoperatively,optical coherence tomography(OCT)was used to classify SRF into three patterns:bleb-like loculated(BL),shallow-diffused(SD),and multiple blebs(MB).Serial OCT imaging was used to evaluate morphological changes in SRF until its complete disappearance.Patients were divided into two groups depending on the presence or absence of persistent SRF.RESULTS:A total of 59 patients(59 eyes)were included.There were no statistical differences between two groups at baseline,except for the proportion of patients with high myopia and a younger age.One month after surgery,OCT detected persistent SRF in 49 eyes(83.1%).The 3 morphological patterns of SRF were observed in 27 eyes(55.1%)with BL,13 eyes(26.5%)with SD,and 9 eyes(18.4%)with MB.The mean time for complete absorption differed significantly across the three SRF patterns(F=8.097,P=0.001),which was 8.8±6.1,20.1±12.1,and 16.7±10.2 mo in BL,SD,and MB,respectively.In 9 of the 13 eyes with SD,the pattern transformed into MB type.In cases involving MB,the size and number of blebs decreased gradually until they had been completely absorbed.Eyes with persistent SRF were more likely to demonstrate disruption of the ellipsoid zone(49.0%vs 10%,P=0.034).The final best-corrected visual acuity of two groups was 0.37±0.11(with SRF)vs 0.34±0.12(without SRF)logMAR(P=0.499),respectively.CONCLUSION:High preoperative myopia and younger age are associated with persistent SRF.BL is the most commonly observed pattern with the shortest duration and gradually disappeared.Most cases involving SD SRF transform into MB type during resolution.The size and number of the MBs decrease gradually until they were completely absorbed.The absence of persistent SRF may contribute to slow visual recovery in the short-term but does not influence the final visual outcome.

Advances in the treatment of rhegmatogenous retinal detachment

The pathogenesis of rhegmatogenous retinal detachment depends on three factors, namely, retinal rupture, vitreous liquefaction and traction causing the retina to separate from the pigment epithelium, among which retinal rupture is the most important. Retinopathy is caused by a gap between the neurosensory retina and the retinal pigment epithelium, which severely damages the visual function of the patient. Therefore, early clinical discovery, prevention and selection of an appropriate treatment are important. This article reviews progress in the treatment of retinal detachment.

Concurrent removal of intravitreal lens fragments after phacoemulsification with pars plana vitrectomy prevents development of retinal detachment

AIM: To evaluate the outcomes of "concurrent vitrectomy" to retrieve dislocated lens fragment during phacoemulsification.METHODS: In a retrospective, observational case series, data of patients who underwent "concurrent" pars plana vitrectomy(PPV) for dislocated lens fragments between the period 2000 and 2008 were reviewed. Data collected included patient demographics, pre-operative visual acuity, intra-operative occurrence of retinal breaks, duration of follow up, post-operative intraocular pressure, final best-corrected visual acuity(BCVA),presence of cystoid macular edema(CME) and occurrence of rhegmatogenous retinal detachment(RRD).· RESULTS: A total of 58 eyes of 58 patients were included in the study. At 12 mo the mean postoperative BCVA was log MAR 0.17(20/30) with a range of log MAR0 to 0.69(20/20 to 20/100), with 96.6%(56/58) of patients showing post- operative improvement in visual acuity(P =0.005). None of the patients developed postoperative retinal detachment, endophthalmitis or non-resolving uveitis at 12 mo.CONCLUSION: Our study results suggest concurrent PPV for retained lens fragments after cataract surgery is beneficial and may decrease the risk of glaucoma and prevent development of RRD.