The change of microglia numbers within the mice retina, optic nerve and chiasm following intravitreal AAV2-GFP injection

Purpose To explore the optimized concentration of AAV2-GFP for sparse transfection of retinal ganglion cells (RGCs) and optic nerve (ON), and to examine the changes of microglial morphology and distribution in the retina, optic nerve and chiasm after injection. Methods We defined the optimal concentration of AAV2-GFP for sparse labeling of RGCs and axons in WT mice. We further explored the changes of microglial morphology and distribution in the retina, optic nerve and chiasm after intravitreal injection in CX3CR1+/GFP mice. Results 14 days after intravitreal injection of AAV2-GFP, live imaging of the retina showed that fundus fluorescence was very strong and dense at 2.16 × 1011 VG/retina, 2.16 × 1010 VG/retina, 2.16 × 109 VG/retina. RGCs were sparsely marked at a concentration 1:1000 (2.16 × 108 VG/retina) and fundus fluorescence was weak. The transfected RGCs and axons were unevenly distributed in the retina and significantly more RGCs were transfected near the injection site of AAV2-GFP compared to the other sites of the flat-mounted retina. Microglia density increased significantly in the retina and part of optic nerve, but not in the optic chiasm. The morphology of microglia was largely unchanged. Conclusions AAV2-GFP was highly efficient and the optimal concentration of sparsely labeled RGCs was 1:1000 (2.16 × 108 VG/retina). After intravitreal injection of AAV2-GFP, the number of microglia increased partly. The morphology of microglia was comparable.

The Effects of Intravitreal Agents on Systemic Vascular Diseases in Patients with Diabetic Retinopathy

Purpose: To assess the risk for cerebrovascular desease (CVD) and coronary artery disease (CAD) in diabetic patients who were treated with intravitreal anti-VEGF agents and compare the rates of CVD and CAD with diabetic controls. Methods: A retrospective chart review of diabetic patients was performed. The need for intravitreal injection and type of agent were noted. If clinically significant or center-involving diabetic macular edema (DME) were determined, intravitreal anti-VEGF agents were used. The CVD and/or CAD occurred within 6 months of the intravitreal injection were accepted as the main outcomes of the study. The records of diabetic patients who were followed up but not needed intravitreal injections were accepted as the control group of the study. Comparisons between these groups were performed.Results: The number of patients enrolled in the study was 9751 (5243 female, 4508 male patients). Of these patients, 1261 patients were received various intravitreal injections. Patients who had CVD history were divided into two groups according to whether they received intravitreal injection or not. There was statistically significant difference between these groups in terms of CVD history (p<0,001). There was statistically significant difference in the hazard of CVD between different anti-VEGF treatments (p<0,001). Patients who had CAD history were divided into two groups according to whether they received intravitreal injection or not. There was no statistically significant difference between these groups in terms of CAD history (p=0,31). Discussion: The risk for CVD was seen to increase with the intravitreal anti-VEGF treatment in diabetic patients. The rate of CVD was higher in patients who received intravitreal bevacizumab treatment.

Intravitreal injection is associated with increased posterior capsule rupture risk during cataract surgery: A meta-analysis

Background: Although observational studies have suggested that prior intravitreal therapy may predict posterior capsule rupture (PCR) during cataract surgery, this finding is still controversial. Objective: To summarize current evidence on the association between prior intravitreal injection (IVI) and PCR during cataract surgery. Methods: A systematic literature search was performed up to October 27th, 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models. The potential association between IVI and PCR in future cataract surgeries was assessed using the following two models: “pooling the odds ratios of PCR in eyes with and without previous IVI(s)” and “pooling the odds ratios for PCR relative to each increase in the number of prior injections.” The quality of included studies was appraised using the Newcastle-Ottawa Scale. Results: 6 cohort studies were included in this meta-analysis, with a total of 1,051,097 eyes that underwent cataract surgery. Of these, 7,034 eyes were associated with previous IVI. The pooled odds of PCR in eyes with prior IVI was 2.01 (95% CI: 1.35–3.00) times higher than that of eyes without an IVI history. An increase in the number of previous IVI conferred increased odds of PCR of 1.03 (95% CI: 1.01–1.06). After excluding studies that failed to account for confounders, the significantly increased risk was not altered, and the significant heterogeneity was minimized in both models. Conclusion: This meta-analysis provides evidence that previous IVI significantly increases the risk of PCR during future cataract surgery. The risk of PCR should be discussed preoperatively with patients. Further studies are required to validate our findings and explore the underlying mechanisms.

Case Report: A Case of Cotton-Wool Spots After Intravitreal Injection of Conbercept in an Infant With Incontinentia Pigmenti

Introduction: Incontinentia pigmenti (IP) is a rare X-linked neuroectodermal dysplasia affecting multiple organs. One of its most significant ophthalmic manifestations is retinal neovascularization due to retinal ischemia, which has been traditionally treated with laser photocoagulation or cryotherapy. The application of anti-vascular endothelial growth factor (VEGF) has been reported for the treatment of retinopathy of IP with beneficial results. However, clinicians should be aware of the possible ocular and systemic side effects of the intravitreal injection of anti-VEGF agents.Case Report: A 4-month-old female infant with IP was treated with intravitreal injection of conbercept in both eyes. However, cotton-wool spots were noticed in the left eye 1 week after the injection. Laser photocoagulation was performed as an adjunct treatment. The cotton-wool spots were absorbed 1 month after the first intravitreal injection and have eventually disappeared.Discussion: The cotton-wool spots, after intravitreal injection of conbercept for the treatment of IP, indicated severe retinal ischemia resulting from the neutralization of excessive VEGF, which was shown on fundus photograph and fluorescent angiography. Anti-VEGF agents could cause retinal arteriolar vasoconstriction and artery occlusion on rare occasions. The administration of anti-VEGF agents in pediatric cases with severe neovascularization and retinal ischemia should be carefully considered.