Circulating Small Extracellular Vesicles Involved in Systemic Regulation Respond to RGC Degeneration in Glaucoma.

Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) degeneration and vision loss. Since irreversible neurodegeneration occurs before diagnosable, early diagnosis and effective neuroprotection are critical for glaucoma management. Small extracellular vesicles (sEVs) are demonstrated to be potential novel biomarkers and therapeutics for a variety of diseases. In this study, it is found that intravitreal injection of circulating plasma-derived sEVs (PDEV) from glaucoma patients ameliorated retinal degeneration in chronic ocular hypertension (COH) mice. Moreover, it is found that PDEV-miR-29s are significantly upregulated in glaucoma patients and are associated with visual field defects in progressed glaucoma. Subsequently, in vivo and in vitro experiments are conducted to investigate the possible function of miR-29s in RGC pathophysiology. It is showed that the overexpression of miR-29b-3p effectively prevents RGC degeneration in COH mice and promotes the neuronal differentiation of human induced pluripotent stem cells (hiPSCs). Interestingly, engineered sEVs with sufficient miR-29b-3p delivery exhibit more effective RGC protection and neuronal differentiation efficiency. Thus, elevated PDEV-miR-29s may imply systemic regulation to prevent RGC degeneration in glaucoma patients. This study provides new insights into PDEV-based glaucoma diagnosis and therapeutic strategies for neurodegenerative diseases.

Effect of intubation in patients with functional epiphora after endoscopic dacryocystorhinostomy.

AIM: To investigate the effect of bicanalicular silicone tube intubation (BSTI) in the treatment of functional epiphora after endoscopic dacryocystorhinostomy (En-DCR). METHODS: Clinical data of 84 patients (95 eyes) with functional epiphora after En-DCR were retrospectively analyzed. Functional epiphora was confirmed as persistent or recurrent epiphora by fluorescein dye disappearance test (FDDT), lacrimal irrigation test, as well as endoscopic examination. Secondary BSTIs were recommended for patients with functional epiphora. These tubes were removed 1mo after surgery. Functional success and associated complications were assessed after 2y of follow-up. RESULTS: Seven patients (9 eyes) refused intervention, 5 patients (6 eyes) did not complete postoperative follow-up, and 1 patient (1 eye) developed tube prolapse within 1mo after surgery. Seventy-one patients (79 eyes) were included at last. Functional success ratios at six months, one year, as well as two years post-operation were 94.9% (75/79), 92.4% (73/79), and 91.1% (72/79), respectively. Three eyes presented with punctal slitting (2 eyes without epiphora), 1 eye with proximal canaliculus slitting, 1 eye with canaliculus stenosis and 4 eyes with still present functional epiphora without detectable abnormal at the last follow-up. CONCLUSION: Secondary intubation is an effective procedure with low recurrence probability for functional epiphora after En-DCR. Punctal and canaliculus injury are the main tube-associated complications after secondary intubation.

Endoscopic dacryocystorhinostomy with mucosal anastomosing in chronic dacryocystitis with three categories of ethmoid sinuses.

AIM: To evaluate the outcome of endoscopic dacryocystorhinostomy (En-DCR) with mucosal anastomosis in chronic dacryocystitis patients, with various categories of ethmoid sinuses. METHODS: Between July 2015 and September 2019, 1439 adult patients, representing 1623 affected eyes, presented with chronic dacryocystitis and were scheduled for En-DCR. The categories of ethmoid sinuses were preoperatively determined, using computed tomography-dacryocystography (CT-DCG), and were classified as category 1 (C1), category 2 (C2), and category 3 (C3). No sinuses anterior to the posterior lacrimal crest defined as C1. Sinuses found between the anterior edge of the lacrimal bone and the posterior lacrimal crest defined as C2. Sinuses found anterior to the lacrimal bone suture defined as C3. At the end of surgery, the dacryocyst and nasal mucosa were anastomosed in C1, and the dacryocyst mucosa and anterior ethmoid sinus were anastomosed in C2 and C3 ethmoid sinus patients. The surgical success rate and related complications, in patients with 3 categories of ethmoid cells, were monitored and documented. RESULTS: Postoperative data was obtained for 179 C1 affected eyes, 878 C2 affected eyes, and 432 C3 affected eyes. The overall success rate of En-DCR was 93.0% (1385/1489). Additionally, the success rates were comparable among the different ethmoid categories at 12mo post operation. We demonstrated that the major reason for surgical failure was intranasal ostial closure, due to granulation or scar tissue. CONCLUSION: En-DCR is a feasible and highly effective primary treatment for chronic dacryocystitis. To ensure surgical success, the surgery protocol must be designed in accordance with the category of ethmoid sinuses present in individual patient.

Management of chronic dacryocystitis cases after failed external dacryocystorhinostomy using endoscopic technique with a novel lacrimal ostium stent.

AIM: To demonstrate the outcomes of endoscopic endonasal dacryocystorhinostomy (En-DCR) with an novel lacrimal ostium stent (LOS) which was performed in patients with recurrent epiphora after failed external dacryocystorhinostomy (Ex-DCR) and analyze the causes of failed Ex-DCR. METHODS: From September 2015 and December 2017, the clinic data of 29 cases suffered from recurrent epiphora after failed Ex-DCR was reviewed. The LOS were implanted into the ostium at the end of the revisional surgery. The causes of failed Ex-DCR were analyzed before revisional surgeries. Outcome of revisional surgeries with the new device were evaluated as well. RESULTS: The major causes of failure of the external approach were synechiae formation in the nasal ostium (29/29), followed by inadequate removal of the bony wall (21/29), nasal synechiae formation between lateral wall of nose and middle turbinate (11/29), and the bone opening was not in good location (7/29). The rate of success after revisional surgery was 82.76%. Re-obstruction of the ostiums were found in 5 failed cases. CONCLUSION: Endoscopic approach with a novel LOS may be an effective procedure to manage recurrent epiphora after previous failed Ex-DCR surgery. Synechiae formation in the nasal ostium and inadequate removal of the bony wall were the major causes of failure of Ex-DCR.

Therapeutic difference between orbital decompression and glucocorticoids administration as the first-line treatment for dysthyroid optic neuropathy: a systematic review.

To assess all available data to compare the efficacy of glucocorticoids treatment and orbital decompression for dysthyroid optic neuropathy (DON). PubMed, EMBASE, the Cochrane Library databases as well as other sources were searched by two independent reviewers followed by extensive hand-searching for the identification of relevant studies. The primary outcomes were the improvement in visual acuity and responder rate. Secondary outcomes were the proptosis reduction, change in diplopia, and clinical activity score (CAS). One randomized controlled trial, three retrospective case series and one prospective case series met the inclusion criteria. They were divided into intravenous high-dose glucocorticoids (ivGC) group and orbital decompression (OD) group. Both groups demonstrated improvement in visual acuity. In addition, the proportion of patients with improved vision in OD group was higher than that in ivGC group (P<0.001). Post-treatment proptosis reduction was also reported in both groups. Overall, weighted mean in proptosis reduction estimated at 1.64 and 5.45 mm in patients treated with ivGC and OD respectively. This study also presented results regarding pre-existing and new-onset diplopia. Apart from diplopia, a wide variety of minor and major complications were noted in 5 included studies. The most common complication in ivGC group and OD group was Cushing's syndrome and epistaxis respectively. The present systematic review shows that both glucocorticoids treatment and OD are effective in treating DON and OD may work better in improving visual acuity and reducing proptosis. However, high-quality, large-sample, controlled studies need to be performed in the future.

Surgical outcomes in acute dacryocystitis patients undergoing endonasal endoscopic dacryocystorhinostomy with or without silicone tube intubation.

AIM: To establish the necessity of silicone tube intubation in acute dacryocystitis (AD) patients undergoing endonasal endoscopic dacryocystorhinostomy (En-DCR). METHODS: Patients presenting with unilateral AD were randomly assigned to two treatment groups. En-DCR procedures were performed following lacrimal abscess formation, with the operation being performed with silicone intubation for patients in group B but not group A. Functional success was defined by an absence of additional AD episodes, no epiphora, and ostium patency as established via endoscopic evaluation or fluorescein irrigation. Operative success rates and demographic variables were compared between treatment groups. RESULTS: In total, 66 patients were analyzed in the present study (33 per group), with complete postoperative data having been successfully collected from 27 and 22 patients in group A and group B, respectively. All patients exhibited complete resolution of acute inflammation. Upon follow-up, granulation tissue was detected around the ostium at higher rates in group B (9/22, 40.9%) relative to group A (4/27, 14.8%). At the 12-month follow-up time point, patients in group A exhibited higher success rates (25/27, 92.6%) relative to patients in group B (20/22, 90.9%), but this difference was not significant. Cases of lacrimal passage reconstruction failure in both groups were attributed to excessive fibrous and/or granulation tissue formation proximal to the intranasal ostium. CONCLUSION: Given that these two operative approaches are associated with similar rates of operative success and in light of differences in granulation tissue formation, cost, and operative duration, these data do not support the routine silicone intubation of AD patients following En-DCR surgery.

Endoscopic transnasal canaliculorhinostomy for refractory common canalicular obstruction with an unidentifiable lacrimal sac.

AIM: To describe the role of endoscopic transnasal canaliculorhinostomy (ETC) in refractory common canalicular obstruction (CCO) associated with an absent or unidentifiable lacrimal sac. METHODS: The records of patients with refractory CCO who underwent ETC at the Eye Hospital of Wenzhou Medical University from October 2007 to December 2016 were retrospectively reviewed. RESULTS: Fifty-six patients (56 eyes) with refractory CCO were recruited into the study. Eight patients were excluded due to the presence of a residual lacrimal sac or failure to complete the follow-up duration. The anatomic and functional success rates were both 85.4% (41/48) at a mean follow-up of 18.6mo. Five cases failed as a result of ostial synechia and two failed because of ostial obstruction by granulation. Postoperative complications included mild nasal bleeding in 5 cases, dried nasal feeling in 8 cases, and olfactory dysfunction in 4 cases. CONCLUSION: Although being surgically challenging, ETC has comparable findings to its external approach counterpart or conjunctivodacryocystorhinostomy (CDCR) with Jones tube. And it may prove to be a novel alternate surgical technique for patients with refractory CCO without identifiable lacrimal sac.

Predictive parameters on CT scan for dysthyroid optic neuropathy.

AIM: To evaluate the value of parameters on CT scan in predicting dysthyroid optic neuropathy (DON) and to provide guidance for early diagnosis of DON accordingly. METHODS: A total of 67 eyes of 35 patients with thyroid-associated ophthalmopathy (TAO) were included in this study. Patients were divided into 2 groups (DON group and non-DON group). Parameters were measured on high resolution CT, including muscle index (MI), superior ophthalmic vein (SOV) dilatation, extraocular muscle volume/orbit volume (MV/OV), and intracranial fat prolapsed, and be compared between these 2 groups. The relation between those parameters and visual function [visual acuity (VA) and visual field defect (VF defect)] were also evaluated. RESULTS: MI and MV/OV were significantly higher in DON group (P=0.00035 and P=0.00026). No significant difference was detected regarding intracranial fat prolapse existence and SOV dilatation (P=0.37 and P=0.15). MV/OV was found to have significant negative correlation with both VF defect (R=-0.332, P=0.0273) and VA (R=-0.635, P=0.00) while MI was found to have negative linear correlation with VA only (R=-0.456, P=0.00017). The area under receiver operating characteristic curves was 0.82 for MV/OV and 0.75 for MI. The best performance in detecting DON was achieved when MV/OV is set at 0.20 with 72% sensitivity and 87% specificity and MI is set at 0.52 with 64% sensitivity and 80% specificity. CONCLUSION: MI and MV/OV are predictive parameters for DON. Together with clinical manifestations, MV/OV≥0.2 can be used as a good indicator for DON in TAO patients.

Newly onset indirect traumatic optic neuropathy-surgical treatment first versus steroid treatment first.

AIM: To investigate the efficacy and safety of the treatment of endoscopic trans-ethmosphenoid optic canal decompression (ETOCD) with combination of steroid in patients with newly onset indirect traumatic optic neuropathy (ITON) and compare the outcome between immediate ETOCD treatment and ETOCD with preoperative steroid treatment. METHODS: Patients presented as newly onset ITON (suffered trauma within 3d) at a tertiary medical center between Mar 1st, 2016 and Mar 1st, 2018 were enrolled in this study. All patients were equally and randomly divided into 2 groups. Cases in group A were performed ETOCD immediately after admition while cases in group B were prescribed by methylprednisolone (20 mg/kg · d) for 3d before ETOCD. Methylprednisolone (20 mg/kg · d) was used after surgery for 6d in group A and 3d in group B. Follow-up was up to 3mo in all cases. Visual acuity (VA) before and after treatment between the two groups were taken into comparison. RESULTS: Complete postoperative data were acquired from 34 patients in group A and from 32 patients in group B. Group A had significantly higher effective rate in VA than group B (χ 2=4.905, P=0.027). CONCLUSION: For patients with newly onset ITON, combination treatment of ETOCD with high-dose steroid is an effective and safe way. Immediate surgery will lead to better prognosis for these cases.

The novel chalcone analog L2H17 protects retinal ganglion cells from oxidative stress-induced apoptosis.

Chalcone is a plant metabolite widely found in fruits, vegetables, spices and tea, and has anti-tumor, anti-inflammation, immunomodulation, antibacterial and anti-oxidation activities, as well as many other pharmacological and biological effects. Our team has shown that its analogs have antioxidant activity, and oxidative stress is a pathological hallmark of retinal ischemia/reperfusion injury that can lead to retinal damage and visual loss. This investigation aims to identify a chalcone that protects retinal ganglion cells in vitro from the effects of oxidative stress and examine its mechanism. Rat retinal ganglion cell-5 cells were pretreated with chalcones and then exposed to tert-butyl hydroperoxide that causes oxidative damage. Controls received dimethyl sulfoxide only or tert-butyl hydroperoxide in dimethyl sulfoxide. Only (E)-3,4-dihydroxy-2'-methylether ketone (L2H17), of the five chalcone analogs, markedly increased the survival rate of oxidatively injured RGC-5 cells. Thus, subsequent experiments only analyzed the results of the L2H17 intervention. Cell viability and apoptosis were measured. Intracellular superoxide dismutase and reactive oxygen species levels were used to assess induced oxidative stress. The mechanism of action by L2H17 was explored by measuring the ER stress/UPR pathway and the expression and localization of Nrf2. All results demonstrated that L2H17 could reduce the apoptosis of oxidatively injured cells, inhibit caspase-3 activity, increase Bcl-2 expression, decrease Bad expression, increase the activity of superoxide dismutase, inhibit the production of reactive oxygen species, increase Nrf2 immunoreactivity, and reduce the activating transcription factor 4, phospho-eukaryotic initiation factor 2 and CHOP expression. L2H17 protects retinal ganglion cells induced by oxidative stress by regulating Nrf2, which indicates that it has the potential to become a drug for retinal ischemia/reperfusion.

Prognostic factors of trans-ethmosphenoid optic canal decompression for indirect traumatic optic neuropathy.

AIM: To investigate a possible correlation between visual acuity (VA) prognosis and the presence at baseline of various orbital and ocular signs in patients affected by indirect traumatic optic neuropathy (ITON). METHODS: From July 1st, 2012 to July 1st, 2015, 224 adults diagnosed with ITON who underwent endoscopic trans-ethmosphenoid optic canal decompression (ETOCD) were reviewed. Visual outcome before and after treatment were taken into comparison. RESULTS: Accompanied older in age, longer time to medical treatment and existence of optic canal fracture (OCF) were the independent predictors for poor postoperative VA and lower improvement degree of visual acuity (IDVA), while worse preoperative VA was predictive factor for poor postoperative VA only. Mean value of IDVA in patients with OCF was 0.19±0.30. Mean value of IDVA in patients without OCF was 0.29±0.35. IDVA in cases without OCF was significant higher than those with OCF (t=2.272, P<0.05). CONCLUSION: Patients suffered from ITON without OCF before ETOCD have better surgical outcome than those with OCF. Older in age, longer time to medical treatment and existence of OCF are independent factors for poor VA prognosis and lower IDVA. Preoperative VA is independent factor for VA prognosis only.

New mucosal flap modification for endonasal endoscopic dacryocystorhinostomy in Asians.

AIM: To describe a simple modification of fashioning the mucosal flap for endonasal endoscopic dacryocystorhinostomy (EES-DCR) in Asians and investigate its efficacy. METHODS: A total of 120 patients with unilateral primary chronic dacryocystitis (PCD) were randomized into two groups: the new shaped nasal mucosal flap group (group A) and the removed nasal mucosal flap group (group B). All patients underwent standard EES-DCR. Patients in group A were performed a new shaped nasal mucosal flap covering the bared bone around the opened sac and those in group B was removed the nasal mucosal flap uncovering the bared bone. Patients were followed up for one year. The occurrence of granulation tissue, the proliferation of scar tissue and success rate of EES-DCR was compared. RESULTS: In the present study, complete postoperative data were acquired from 54 patients in group A and from 57 patients in group B. During process of review, the occurrence of granulation tissue was at the ostium margins account for 15% (8/54) in group A and 39% (22/57) in group B (P<0.05). At the one-year review, scar tissue was present in 5 patients in group A compared with 18 in group B (P<0.05). The success rate of EES-DCR was 98% (53/54) in group A and 84% (48/57) in group B (P<0.05). CONCLUSION: The simple modification of fashioning nasal mucosal flap can effectively cover the bared bone around the opened sac and reduce formation of granulation tissue, lessen the risk of scar tissue formation and closure of ostium, thus improve the success rate of EES-DCR in Asians.

[Endoscopic trans-ethmoid medial orbital wall decompression combined with intraconal fat decompression for Graves' ophthalmopathy].

OBJECTIVE: To present a new mini-invasive surgery for compressive optic neuropathy (CON) in Graves' ophthalmopathy (GO) by adequately decompressing the orbital apex and correcting proptosis, and to analyze its results. METHODS: A retrospective chart was reviewed in 29 patients receiving orbital decompression for the treatment of CON secondary to GO from October 2006 to May 2011. All patients diagnosed CON were in stable and inactive phase of GO at least for 6 months. All patients received endoscopic transethmoid medial orbital wall decompression to reduce the compression on the orbital apex. In the meanwhile, an endoscopic transethmoid intraconal fat-removal orbital decompression was performed to remove parts of intraconal fat with a special aspiration/cutting instrument to further reduce the proptosis. All patients were followed up periodically. RESULTS: of improvement of visual acuity (VA), color vision, and amount of proptosis reduction and incidence of induced diplopia 9 months after surgery was recorded for analysis its feasibility. RESULTS: Forty-five orbits of 29 patients were included in the study. At the 9 months review, 44 of 45 eyes (97.8%) improved their VA from -0.65±0.30 (x±s) preoperatively to -0.24±0.22, with a mean improvement of 0.55±0.17 (t=-13.012, P<0.001), 23 of 29 eyes (79.3%) had improved color vision (P<0.001), and the mean reduction in proptosis was (7.07±1.59) mm (range 4-11 mm). Postoperative symmetry to within 2 mm were achieved in all patients. Except 1 patient complaining of deterioration in diplopia following surgery, no patients presented new on-set diplopia postoperatively. CONCLUSION: The endoscopic transethmoid medial orbital wall decompression combined with the endoscopic transethmoid intraconal fat-removal orbital decompression is an effective treatment with minimal morbidity for both visional recovery and improvement of proptosis for CON in GO.

[Ophthalmic complication and management of endoscopic sinus surgery].

OBJECTIVE: To investigate the possible reasons and the treating experiences of ophthalmic complications in order to elevate the attention of the nasal endoscopic surgeon. METHODS: This study was involved 8 categories in 22 cases which had typical characteristic of ophthalmic complications of endoscopic sinus surgery, including injury of lamina papyracea, obstructive cyst of frontal and ethmoid sinuses, orbital infection, injuries of lacrimal passages, injury of extraocular muscles, orbital hemorrhage, optic nerve injury and arterial embolism of optic fundi. The patients were given corresponding treatment. RESULTS: Injury of lamina papyracea was cured by medical treatment while orbital infection, injury of lacrimal passages, obstructive cyst of frontal and ethmoid sinuses were completely recovered by endoscopic surgery. In one of the cases, the injured optic nerve had recovered after transnasal optic and orbital apex decompression but the other 6 sides of 6 patients had not been improved. In one case who had suffered from injury of extraocular muscles, their diplopia disappeared mostly, but the other cases had a slight diplopia after surgery. One case who had visual descending caused by orbital hemorrhage recovered. Two cases of visual loss caused by intraorbital hemorrhage and arterial embolism of optic fundi respectively were not improved. CONCLUSIONS: It is very difficult to cure if the patients lose the sight because of optic nerve injury, orbital hemorrhage and the ischemia of orbit, however, if the patients had remnant vision the prognosis should be much better.

[Dynamic changes of MMP-2 activity in the posterior sclera of chicks with form-deprivation myopia].

OBJECTIVE: To investigate the effect of form-deprivation on level of gelatinase in the posterior sclera in chicks. METHODS: Fifty 1-day-old chicks were monocularly deprived to establish the animal model of form-deprivation myopia (FDM). According to the duration of form-deprivation the experimental chicks were divided randomly and equivalently into 5 groups, which were deprived for 3, 7, 14, 21 and 30 days respectively. Meanwhile the other eyes of the deprived chicks were used as self-control groups and chicks of the same days were chosen randomly as the normal control groups for each FDM group. At each form-deprivation point the changes of degree of diopters and axial length of chicks in each group were recorded. The levels of gelatinase in posterior sclera of the experimental eyes were measured by gelatin enzymography. RESULTS: Compared with the normal and self-control groups, the levels of MMP-2 activity in FDM groups were much higher (P <0.01). With the increase of the time of monocular deprivation these changes became more significant and reached the top after 14 days' deprivation with an inter-group statistical difference (P <0.01). The dynamic changes of MMP-2 activity were the same as those of axial length and degree of diopters in each experimental groups. There was positive correlation between the MMP-2 activity and axial length (r = 0.989, P < 0.01). But there was a negative correlation between the MMP-2 activity and refractive degree. CONCLUSION: Increase of MMP-2 activity in the posterior sclera of chicks would be a direct key factor to trigger sclera ECM remodeling process in chick FDM.

[Matrix metalloproteinase-2 mRNA expression in the posterior sclera of chick form-deprivation myopia].

OBJECTIVE: To investigate the dynamic changes of matrix metalloproteinase-2 (MMP-2) mRNA expression in the posterior sclera of chick form-deprivation myopia (FDM) and its possible molecular mechanism. METHODS: Fifty white 1-day-old leghorn chicks were divided randomly and equally into 5 groups. The right eye of each chick was covered with a plastic goggle at 4, 7, 14, 21, and 30 postborn days respectively to induce FDM, and the left eye served as a self-control. Meanwhile, normal age-matched chicks were provided as negative control speciments for each group. Removing the goggle at every experiment point, refractive status and axial length were determined with streak retinoscopy (without cycloplegia) and A-scan ultra-sonography under topical anaesthesia, respectively. Both eyes were collected after the chicks were killed. The total RNA in the posterior sclera was extracted traditionally using TRIZOL reagent, and then the expression levels of MMP-2 messenger RNA were analyzed by one step reverse transcriptiontase-polymerase chain reaction. RESULTS: Compared with the normal and self-control groups, the expression levels of MMP-2 mRNA in the deprived eyes significantly increased (P < 0.001). With the delay of form-deprivation duration, MMP-2 mRNA expression levels increased significantly and especially reached a highest point at the 14th day of monocular deprivation. After that the level decreased slightly, but maintained at a high level. Although there was no significant difference between the normal control group and the self-control one (P > 0.05), MMP-2 mRNA expressed slightly higher in the self-controlled eyes. CONCLUSION: As a primary element to trigger early active sclera extracellular matrix remodeling process, MMP-2 gene is probably involved in the development of FDM by excessive degradation of extraceller matrix which can make sclera thinner and the eye axis longer.