Development of Uveal Melanoma-Specific Aptamer for Potential Biomarker Discovery and Targeted Drug Delivery.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. However, challenges in early diagnosis, high risk of liver metastasis, and lack of effective targeted therapy lead to poor prognosis and high mortality of UM. Therefore, generating an effective molecular tool for UM diagnosis and targeted treatment is of great significance. In this study, a UM-specific DNA aptamer, PZ-1, was successfully developed, which could specifically distinguish molecular differences between UM cells and noncancerous cells with nanomolar-range affinity and presented excellent recognition ability for UM in vivo and clinical UM tissues. Subsequently, the binding target of PZ-1 on UM cells was identified as JUP (junction plakoglobin) protein, which held great potential as a biomarker and therapeutic target for UM. Meanwhile, the strong stability and internalization capacity of PZ-1 were also determined, and a UM-specific aptamer-guided "nanoship" was engineered to load and selectively release doxorubicin (Dox) to targeted UM cells, with lower toxicity to nontumor cells. Taken together, the UM-specific aptamer PZ-1 could serve as a molecular tool to discover the potential biomarker for UM and to achieve the targeted therapy of UM.

Development of an Aptamer-Based Molecular Tool for Specifically Targeting Microglia via the CD64 Protein.

Microglial dysfunction has been identified as a key factor in the pathology of several traumatic and neurodegenerative diseases in the central nervous system. Due to the importance of microglia in various pathological processes, the development of molecular tools to target microglia may be of significance for the clinical diagnosis and treatment of these disorders. In this study, a DNA aptamer, ZH-1c, that binds microglia with high affinity was developed by cell-SELEX and truncated strategies. ZH-1c exhibits promising binding ability under physiological temperatures, high serum stability after being modified, and can be internalized by microglia. Also, the binding target of ZH-1c on microglia was identified as the transmembrane protein CD64, which increased in response to inflammatory stimulation via lipopolysaccharide and interferon-gamma, thus enhancing the affinity of ZH-1c for activated microglia. Based on the above experiments, the DNA aptamer ZH-1c exhibits great potential for the targeting of activated inflammatory microglia and may be suitable as a novel and effective molecular tool for diagnosis and microglia-targeted therapies.

The spatial-temporal reactive changes of compressed optic nerve in a clinically relevant rabbit model of persistent compressive optic nerve axonopathy.

The optic nerve (ON) can get compressed in different diseases. However, the pathological and functional changes occurring in the compressed ON over time under constant compression are still unclear. In the present study, we implanted an artificial tube around the optic nerve of a rabbit to primarily create a clinically relevant persistent compressive optic nerve axonopathy (PCOA). Due to the protuberance on the inner ring of the tube, steady and persistent compressions were maintained. In this model, we investigated the thickness of ganglion cell complex (GCC), retinal ganglion cell (RGC) density, axon density of optic nerve, flash visual evoked potential (FVEP), and anterograde axonal transport at various times in four different groups viz. the no comp, 1/2 comp, 3/4 comp, and crush groups. The GCC thickness, RGC density, and axon density of ON were hierarchically and significantly decreased in 1/2 comp, 3/4 comp, and crush groups. Compared to no comp eyes, the P2 amplitude ratio of FVEP was significantly decreased in 3/4 comp but not in 1/2 comp eyes. Only a portion of the optic nerve lost the ability of anterograde axonal transport in the 1/2 comp group. However, it was evident at 2-wpo and more prominent at 4-wpo in 3/4 comp eyes. This study reveals that the compression only induces the homolateral ON axons impairment and the proportion of the affected axons maintains the same for mild compression for at least three months. Furthermore, an underlying threshold effect highlights that mild compression does not require urgent surgery, while the severe compression warrants immediate surgical intervention.

Removal of Small Cavernous Hemangioma in Orbital Apex Through an Endoscopic Transethmoidal-Sphenoidal Approach.

OBJECTIVE: To investigate the feasibility, efficacy, and safety of an endoscopic transethmoidal-sphenoidal approach in removing a small cavernous hemangioma (CH) located in the deep lateral orbital apex. METHODS: This study involved 19 patients diagnosed with a CH located in the deep lateral orbital apex. All patients underwent an endoscopic transethmoidal-sphenoidal approach for removal of the CH. The best-corrected visual acuity (BCVA), visual field, and surgery-related complications were analyzed and compared. RESULTS: All tumors in this study were completely removed. The mean BCVA was LogMAR 0.97 ± 0.97 preoperatively and LogMAR 0.38 ± 0.64 postoperatively (p < 0.05). The mean visual field index was 52.26% ± 33.26% preoperatively and 75.47% ± 30.49% postoperatively (p < 0.05). The mean deviation index was -17.48 ± 12.43 dB preoperatively and -10.10 ± 10.85 dB postoperatively (p < 0.05), and the pattern standard deviation was 6.37 ± 3.77 dB preoperatively and 4.90 ± 3.56 dB postoperatively (p > 0.05). Four (21.1%) patients developed oculomotor limitations and two (10.5%) patients developed ptosis after surgery. All of these symptoms resolved spontaneously, and no other complications occurred. The mean follow-up time was 6.71 ± 3.89 months. CONCLUSION: The endoscopic transethmoidal-sphenoidal approach is an effective and minimally invasive treatment for removing small CH in the deep lateral orbital apex. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1743-1749, 2022.

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.

Endoscopic transnasal drainage for orbital implantation cyst after orbital wall reconstruction.

An implantation cyst after orbital wall reconstruction may present as a late complication, which can cause local pain, proptosis, diplopia, and vision impairment. Previous surgical strategies prefer transconjunctival or subtarsal approach for cyst drainage, a similar approach to orbital wall reconstruction. These strategies may have risk of secondary infection. Herein, we propose an endoscopic transnasal surgical approach, through which the removal of implant and cyst drainage can be performed conveniently. The residual, medial single-layer cyst wall is generally strong enough to support the orbital soft tissues without the need for a new implant. We believe this surgical approach can simplify the procedure, reduce the complications, and prevent cyst recurrence.

Self-Cross-Linked Hyaluronic Acid Hydrogel in Endonasal Endoscopic Dacryocystorhinostomy: A Randomized, Controlled Trial.

PURPOSE: To investigate whether self-cross-linked HA hydrogel fill stimulates wound mucosal regeneration and its epithelialization around the ostia to improve long-term ostial patency in endonasal endoscopic dacryocystorhinostomy (En-DCR). METHODS: One hundred and ninety-two patients with unilateral primary chronic dacryocystitis (PCD) were randomized divided into 2 groups: group A (the HA hydrogel group) and group B (the control group). All patients underwent En-DCR. The HA hydrogel group received HA hydrogel filling the ostium at the end of the surgery and the control group received no treatment. The mucosal epithelialization of the wound, the formation of granulation, the formation of scars, and the success rate of ostial patency were compared. RESULTS: Our study included 82 patients in group A and 79 patients in group B. At the 2-week follow up, 74 patients (90.2%) in the group A had a healed ostium with a lining of intact epithelial mucosa. It was higher when compared with 56 patients (70.9%) in group B (X2 = 9.698, P < 0.05). At the 12-month follow up, Granulation were present in 7.3% of patients in group A which was significantly lower than the 19.0% of patients in group B (X2 = 4.831, P < 0.05). No statistical difference was found with scars formation between 2 groups (X2 = 1.607, P = 0.205). The success rate of ostial patency was 89.0% (73/82) in group A and 77.2% (61/79) in group B. The success rate was much higher in group A than group B (X2 = 4.02, P < 0.05). CONCLUSION: Self-cross-linked HA hydrogel may enhance the success rate of En-DCR for PCD by promoting mucosal epithelial healing and preventing excessive granulation.

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.

Navigation-Guided Endoscopy Combined with Deep Lateral Orbitotomy for Removal of Small Tumors at the Lateral Orbital Apex.

PURPOSE: To evaluate the efficacy, feasibility, and safety of the navigation-guided endoscopy combined with deep lateral orbitotomy for removal of small tumors at the lateral orbital apex. DESIGN: A retrospective, noncomparative case series. METHODS: Retrospective analysis of ten patients (10 eyes) with small tumors at the lateral orbital apex comprised navigation-guided endoscopy combined with deep lateral orbitotomy at the Eye Hospital of Wenzhou Medical University from November 2015 to November 2017. In each case, the indication of surgery was existing or imminent visual impairment due to the tumor. The removal was believed to be complete if the mass was removed intactly during the surgery. The tumor character was confirmed by pathological examination after surgery. Patients were followed up to 3 months after surgery. Best corrected visual acuity before and after surgery was compared. RESULTS: All tumors were completely removed by the navigation-guided endoscopic approach. The mean preoperative best corrected visual acuity was 6/15 (95% confidence interval (95% CI) 6/40-6/8.5), and the mean postoperative best corrected visual acuity was 6/10 (95% CI 6/15-6/7.5). 5 of 7 (71%) patients with vision loss gained visual improvement in different degrees after surgery, and the rest of the patients had preoperative best corrected visual acuity. Visual field of all patients also improved. 8 cavernous hemangiomas and 2 schwannomas were confirmed postoperatively by pathology. 4 patients accompanied with limitation of eye abduction, which recovered spontaneously in an average of 4 weeks. No other serious complications occurred. CONCLUSIONS: Navigation-guided endoscopy combined with deep lateral orbitotomy seems to be a feasible, efficient, and safe approach for removing small tumors at the lateral orbital apex. This trial is registered with ChiCTR1800019244.

Optic Canal Decompression With Unexpected Changes in Cerebrospinal Fluid of the Optic Canal.

Optic neuritis is a common inflammatory disease of the optic nerve. And the cerebral spinal fluid (CSF) in the subarachnoid space of optic nerve is thought to be homogeneous as in spine. We report a case of optic neuritis, some unexpected opaque fluid observed to flow out from the optic canal during the optic canal decompression surgery when the CSF in spine is normal. One day after the surgery, the visual acuity of the patient improved dramatically to 0.4 from 0.05. This report highlights the possible restrictive pathological changes of the CSF in the optic nerve of acute optic neuritis, which may be the reason of the dysfunction of the optic nerve.