The Optimization of an Anti-VEGF Therapeutic Regimen for Neovascular Glaucoma

This study investigates the safety and efficacy of conbercept injection through different routes for neovascular glaucoma (NVG) treatment, in which seventy-four patients (81 eyes) with NVG caused by ischemia retinopathy had participated. Patients were divided into three stages according to the progression of NVG and were randomly assigned to receive intracameral or intravitreal conbercept injection. After conbercept injection, patients experienced improved best-corrected visual acuity (BCVA), good intraocular pressure (IOP) control, and neovascularization of Iris (NVI) regression. In stage III, patients required trabeculectomy with mitomycin C plus pan-retinal photocoagulation (PRP) to achieve complete NVI regression. Compared to the intravitreal group, the intracameral group had significantly lower IOP in 2 days in stage III and 1 day in stages I and II after injection, complete NVI regression before PRP in stages I and II, and better NVI regression in stage III. The rates of hyphema after trabeculectomy and malfunction filtering bleb suffering needle bleb revision were lower in the intracameral group, but only the hyphema rate was significantly different. Injections through different routes are all safe. We recommend intravitreal injections for patients in stages I and II, but for stage III, intracameral injection is better, and trabeculectomy with mitomycin C should be conducted within 2 days after injection to maximally reduce the risk of perioperative hyphema.Trial Registration:ClinicalTrials.gov, identifier NCT03154892.

Successful Treatment of Post-Phacoemulsification Descemet’s Membrane Detachment Assessed by Anterior Segment Optical Coherence Tomography: A Case Report

Descemet’s membrane detachment (DMD) is a rare but serious complication of phacoemulsification surgery. A small DMD may resolve spontaneously, but extensive DMD often requires intracameral injection of air, nonexpansile gases, or expansile gases. A 92-year-old man who underwent phacoemulsification and aspiration with intraocular lens placement in the right eye had significantly reduced visual acuity, with a hazy cornea after surgery. Anterior segment optical coherence tomography (AS-OCT) examination revealed extensive DMD throughout the cornea. He was treated with intracameral injection of 20% sulfur hexafluoride. As a result, the Descemet membrane was successfully reattached, and the corneal edema resolved. AS-OCT was helpful in confirming the presence and extent of DMD, provided useful information to determine the appropriate treatment, and was useful for monitoring DMD.

Proliferation Increasing Genetic Engineering in Human Corneal Endothelial Cells: A Literature Review

The corneal endothelium is the inner layer of the cornea. Despite comprising only a monolayer of cells, dysfunction of this layer renders millions of people visually impaired worldwide. Currently, corneal endothelial transplantation is the only viable means of restoring vision for these patients. However, because the supply of corneal endothelial grafts does not meet the demand, many patients remain on waiting lists, or are not treated at all. Possible alternative treatment strategies include intracameral injection of human corneal endothelial cells (HCEnCs), biomedical engineering of endothelial grafts and increasing the HCEnC density on grafts that would otherwise have been unsuitable for transplantation. Unfortunately, the limited proliferative capacity of HCEnCs proves to be a major bottleneck to make these alternatives beneficial. To tackle this constraint, proliferation enhancing genetic engineering is being investigated. This review presents the diverse array of genes that have been targeted by different genetic engineering strategies to increase the proliferative capacity of HCEnCs and their relevance for clinical and research applications. Together these proliferation-related genes form the basis to obtain a stable and safe supply of HCEnCs that can tackle the corneal endothelial donor shortage.

Distribution of Gold Nanoparticles in the Anterior Chamber of the Eye after Intracameral Injection for Glaucoma Therapy

In glaucoma therapy, nanoparticles (NPs) are a favorable tool for delivering drugs to the outflow tissues of the anterior chamber of the eye where disease development and progression take place. In this context, a prerequisite is an efficient enrichment of NPs in the trabecular meshwork with minimal accumulation in off-target tissues such as the cornea, lens, iris and ciliary body. We evaluated the optimal size for targeting the trabecular meshwork by using gold NPs of 5, 60, 80 and 120 nm with a bare surface (AuNPs) or coated with hyaluronic acid (HA-AuNPs). NPs were compared regarding their colloidal stability, distribution in the anterior chamber of the eye ex vivo and cellular uptake in vitro. HA-AuNPs demonstrated an exceptional colloidal stability. Even after application into porcine eyes ex vivo, the HA coating prevented an aggregation of NPs inside the trabecular meshwork. NPs with a diameter of 120 nm exhibited the highest volume-based accumulation in the trabecular meshwork. Off-target tissues in the anterior chamber demonstrated an exceptionally low gold content. Our findings are particularly important for NPs with encapsulated anti-glaucoma drugs because a higher particle volume would be accompanied by a higher drug payload.

Accidental Corneal Intrastromal Intraocular Lens Implantation with the Wound-Assisted Technique and Clinical Course with Anterior Segment Optical Coherence Tomography

Accidental intraocular lens (IOL) implantation into the corneal stroma is a rare clinical entity that can occur during the wound-assisted technique. In this report, we describe a case of an 81-year-old man who underwent cataract surgery in which the IOL was implanted into the corneal stroma with the wound-assisted technique, and we present changes in anterior segment optical coherence tomography. The IOL was removed and reinserted after widening the incision. Air tamponade was created by intracameral injection. An anterior chamber tap was performed 10 h later to reduce increased intraocular pressure. Interlayer separation of the corneal stroma was confirmed 30 min postoperatively but was corrected 4 days later. The patient’s best-corrected visual acuity (BCVA) was logMAR 0.30, and he had been diagnosed with age-related macular degeneration before surgery. Although the opacity of the corneal stroma persisted, BCVA improved to logMAR 0. When using the wound-assisted technique for IOL insertion, surgeons should take care not to implant the IOL into the corneal stroma.

Evaluation of the Effectiveness of a Chronic Ocular Hypertension Mouse Model Induced by Intracameral Injection of Cross-Linking Hydrogel

Background: Glaucoma is an irreversible and blinding neurodegenerative disease that is characterized by progressive loss of retinal ganglion cells. The current animal models of glaucoma fail to provide a chronic elevated intraocular pressure and cannot maintain the optical media clarity for a long time, which brings some difficulties to the study of glaucoma. Here, we developed a new chronic ocular hypertension model of mice induced by cross-linking hydrogel intracameral injection.Methods: C57BL/6J mice aged 6–8 weeks were randomly divided into the control group and the operation group. The mice of the operation group were injected with cross-linking hydrogel to induce ocular hypertension. Intraocular pressure was measured preoperatively, 3 days after surgery, and weekly until the end of the study. Flash visual evoked potential (F-VEP) was used to observe optic nerve function at different times (preoperatively and 2, 4, and 6 weeks) after chronic ocular hypertension (COH). Retinal TNF-α, IL-1β, and IL-17A protein expression were measured by western blotting in the control group and in mice at 2, 4, and 6 weeks after COH. Microglial cell activation was evaluated by immunofluorescence staining and western blotting. Apoptosis and loss of retinal ganglion cells after 2, 4, and 6 weeks of intracameral injection of cross-linking hydrogel were observed by the TUNEL assay and Brn3a protein labeling. The loss of optic nerve axons in COH mice was evaluated by neurofilament heavy polypeptide protein labeling.Results: Intracameral injection of the cross-linking hydrogel induces increased intraocular pressure (IOP) to a mean value of 19.3 ± 4.1 mmHg, which was sustained for at least 8 weeks. A significant difference in IOP was noted between COH mice and sham-operation mice (p < 0.0001). The success rate was 75%. The average amplitude of F-VEP in mice with COH was reduced (p = 0.0149, 0.0012, and 0.0009 at 2, 4, and 6 weeks after COH vs. the control group, respectively), and the average latent period in mice with COH was longer (p = 0.0290, <0.0001, and <0.0001 at 2, 4, and 6 weeks after COH vs. the control group, respectively) compared with that in the control group. TNF-α, IL-1β, IL-17A, Iba-1, and CD68 protein expression increased in COH mice. During the processing of COH, the number of microglial cells increased along with cellular morphological changes of rounder bodies and thicker processes compared with the control group. Apoptosis of retinal ganglion cells (RGCs) was clearly observed in mice at 2, 4, and 6 weeks after COH (p = 0.0061, 0.0012, <0.0001, and 0.0371 at 2, 4, and 6 weeks after COH vs. the control group, respectively). The RGC density decreased significantly in the COH mice compared with the control group (p = 0.0042, 0.0036, and <0.0001 at 2, 4, and 6 weeks after COH vs. the control group, respectively). There was a significant loss of optic nerve axons in mice after intracameral injection of cross-linking hydrogel (p = 0.0095, 0.0002, and <0.0001 at 2, 4, and 6 weeks after COH vs. the control group, respectively).Conclusions: A single intracameral injection of cross-linking hydrogel can effectively induce chronic ocular hypertension in mice, which causes progressive loss of retinal ganglion cells, increased expression levels of inflammatory cytokines and microglial cell activation, and deterioration of optic nerve function.

Intracameral anti-VEGF injection for advanced neovascular glaucoma after vitrectomy with silicone oil tamponade

AIM: To evaluate the effect of intracameral injection of conbercept for the treatment of advanced neovascular glaucoma (NVG) after vitrectomy with silicone oil tamponade. METHODS: Conbercept 0.5 mg/0.05 mL was injected into the anterior chamber of 5 eyes, which had developed advanced NVG after vitrectomy with silicone oil tamponade. Then, trabeculectomy with mitomycin C and pan-retinal photocoagulation (PRP) or extra-PRP were conducted within 2d. The follow-up time was 6mo. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), neovascularization of iris (NVI) were recorded before and after treatment. RESULTS: Within 2d after injection, IOP control, and NVI regression were optimal for trabeculectomy. Hyphema occurred in one eye in the process of injection. But none of them present hyphema after trabeculectomy. At the end of follow-up time, all eyes had improved BCVA, well-controlled IOP, and completely regressed NVI. CONCLUSION: Intracameral injection of conbercept is safe and effective in the treatment of patients with advanced NVG after vitrectomy with silicone oil tamponade. Within 2d after injection is the optimal time window for trabeculectomy, which can maximally reduce the risk of perioperative hyphema.

Evaluation of moxifloxacin-induced cytotoxicity on human corneal endothelial cells

Moxifloxacin hydrochloride (MXF) is widely used for the prevention of bacterial endophthalmitis after intraocular surgeries. However, the safety issue of intracameral injection of MXF for human corneal endothelial cells (HCECs) is still debatable. In this study, we investigated concentration-dependent cytotoxicity (0.05–1 mg/ml) of MXF for immortalized HCECs (B4G12 cell) and the underlying mechanism. Reactive oxygen generation (ROS) and cell viability after MXF exposure was measured. Flow cytometric analysis and TUNEL assay was used to detect apoptotic HCECs after MXF exposure. Ultrastructure of damaged HCECs by MXF was imaged by transmission electron microscope. Western blot analysis and caspase 2, 3 and 8 analysis were used to reveal the underlying mechanism of MXF induced damage in HCECs. We found that MXF induced dose-dependent cytotoxicity in HCECs. MXF exposure increased ROS generation and induced autophagy in HCECs. Increased LDH release represented the cellular membrane damage by MXF. In addition, caspases activation, Bax/Bcl-xL-dependent apoptosis pathway and apoptosis inducing factor nuclear translocation were all involved in MXF induced HCECs’ damage, especially after exposure to high dose of MXF (0.5 and 1.0 mg/ml). These findings suggest that MXF toxicity on HCECs should be thoroughly considered by ophthalmologists when intracameral injection of MXF is planned.