Two-year analysis of changes in the optic nerve and retina following anti-VEGF treatments in diabetic macular edema patients.

Purpose: To evaluate long-term structural and functional changes that happen to the optic nerve and retina following ranibizumab (Lucentis) injections in diabetic macular edema (DME) patients. Methods: Patients with clinically significant DME requiring anti-VEGF injections underwent pre-injection baseline, 6, 12, and 24 month follow-up tests. The tests performed were optical coherence tomography (OCT), best-corrected visual acuity (BCVA), and visual field (VF). Wide-field fluorescein angiogram (IVFA) was performed to monitor the progression of diabetic ischemia. Results: A total of 30 patients requiring anti-VEGF injections and 21 control patients not requiring anti-VEGF injections were enrolled in the study. From baseline, the average macular thickness significantly decreased (p<0.0002) over the 24-month time period. Mean perfused ratio significantly increased (p<0.0005) at 6, 12, and 24 months. Cup volume and vertical cup-to-disk ratio significantly increased (p<0.0014) over the study period. This was verified by masked independent grading of patient optic nerve stereo-photographs by glaucoma specialists. BCVA significantly (p<0.0006) improved over the study period. VFs showed a non-significant trend of deteriorating peripheral vision at 12 and 24 months. Conclusion: Clinically, anti-VEGF therapy appears to affect the optic nerve by increasing cup volume and increasing vertical cup/disk ratio over time. The results provide a cautionary note to monitor both the retina and optic nerve status in patients undergoing frequent injections.

Safety of anti-VEGF treatments in a diabetic rat model and retinal cell culture.

PURPOSE: To analyze the safety of different concentrations of anti-VEGF on retinal cells. METHODS: Non-diabetic and streptozotocin (STZ)-induced diabetic rats received intravitreal rat anti-VEGF injections that had final vitreous concentrations of 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL. Rats were also injected with the clinical dose of ranibizumab. TUNEL assay was performed on sectioned eyes to evaluate apoptotic cells. In vitro, rat retinal cell cultures were exposed to 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL of ranibizumab for 48 and 72 hrs. Cellular metabolic activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, necrosis by lactate dehydrogenase (LDH), and apoptosis by cell death enzyme-linked immunosorbent assay (ELISA). RESULTS: Diabetic rats had a significant increase (p<0.03) in apoptotic cell death at half the clinical dose, at the clinical dose, and at double the clinical dose. In vitro, MTT showed a significant decrease (p<0.04) in cellular metabolic activity at the clinical dose and double the clinical dose compared to control at 48 and 72 hrs. LDH showed a significant increase (p<0.04) in necrosis at the clinical dose and double the clinical dose compared to control at 48 and 72 hrs. ELISA showed a significant increase (p<0.04) in apoptosis at half the clinical dose, at the clinical dose, and double the clinical dose, compared to control at 48 and 72 hrs. CONCLUSIONS: Anti-VEGF treatment may be potentially detrimental to the retina by decreasing cellular metabolic activity and increasing cytotoxicity of retinal cells. The results provide a cautionary note to monitor both the retina and optic nerve status in patients undergoing frequent injections.

Risk factors for flat anterior chamber after glaucoma filtration surgery.

AIM: To investigate the incidence rate and risk factors for grade III flat anterior chamber (FAC) after glaucoma filtration surgery based on 5-year data. METHODS: Patients who underwent glaucoma filtration surgery in Daping hospital from January 2009 to December 2013 were enrolled in this retrospective study. The incidence of grade III FAC following glaucoma filtration surgery was determined. Regression analysis was performed to investigate the influence of glaucoma type, surgical approach, age, and preoperative intraocular pressure (IOP) on the risk of postoperative FAC. RESULTS: A total of 2179 eyes receiving anti-glaucoma surgery were included. Ninety-one eyes suffered from postoperative FAC, with an overall incidence rate of 4.18%. Of 471 eyes with primary open angle glaucoma (POAG), grade III FAC occurred in only 3 eyes (0.64%). Primary angle-closure glaucoma (PACG) was diagnosed in 1076 eyes, 39 (3.62%) of which developed grade III FAC, including 12 eyes (12/300, 4%) with acute PACG (aPACG) and 27 eyes (27/776, 3.48%) with chronic PACG (cPACG). Six of 259 eyes (2.32%) with secondary glaucoma, 28 of 186 eyes (15.05%) with neovasular glaucoma, 1 of 66 eyes (1.52%) with congenital glaucoma, and 14 of 115 eyes (12.17%) with remnant glaucoma suffered from grade III FAC. Of 6 eyes with mixed glaucoma, none developed grade III FAC after surgery. When stratified by surgical approach, 24 of 766 eyes (3.13%) undergoing trabeculectomy, 21 of 924 eyes (2.27%) treated by trabeculectomy plus mitomycin C (MMC), 18 of 109 eyes (16.51%) undergoing Ahmed glaucoma valve implantation, 23 of 201 eyes (11.44%) managed by Ahmed implantation plus MMC, and 5 of 133 eyes (3.76%) treated by Ahmed implantation plus lens extraction or vitrectomy developed grade III FAC. Logistic regression analysis revealed that factors including neovasular glaucoma, remnant glaucoma, glaucoma valve implantation, glaucoma valve implantation+MMC, glaucoma valve implantation+vitrectomy, age>60y, and IOP at admission >50 mm Hg were significantly associated with an increased risk for grade III FAC. CONCLUSION: The overall incidence of grade III FAC after glaucoma filtration surgery is 4.18%. Patients with neovasular glaucoma and remnant glaucoma are at a higher risk of developing FAC. Ahmed glaucoma valve implantation is associated with a higher risk for grade III FAC compared with trabeculectomy. No significant correlation was observed between the use of MMC in glaucoma filtration surgery and the risk of postoperative FAC. Higher IOP at admission (>50 mm Hg) and old age (>60y) are risk factors for grade III FAC.

Impression cytology implicates cell autophagy in aqueous deficiency dry eye.

PURPOSE: Impression cytology in combination with a cell autophagy marker was used to demonstrate the utility of a novel frozen section technique, to assess the health of the ocular surface, as well as to correlate autophagic cell death with the commonly used clinical tests for dry eye. METHODS: Female patients over the age of 18 years who attended an outpatient ophthalmology clinic were invited to participate. Schirmer's test, tear film break-up time and the ocular surface disease index questionnaire were used as objective and subjective clinical tests for dry eye. The cellular biomarker microtubule-associated protein light chain 3 (LC3) was used as a marker of autophagic cell death. RESULTS: Low LC3 nuclear staining was positively correlated with Schirmer's test <10 mm. No correlation was found between other clinical tests for dry eye. CONCLUSION: This study demonstrates a positive linear relationship between Schirmer's testing and LC3. There is a lack of correlation between the commonly used diagnostics tests for dry eye, highlighting our incomplete understanding and assessment of dry eye.

Systemic Immunosuppression in High-Risk Penetrating Keratoplasty: A Systematic Review.

Cornea transplantation has a high success rate and typically only requires topical immunomodulation. However, in high-risk cases, systemic immunosuppression can be used. We conducted a systematic review on the efficacy and side effects of systemic immunosuppression for high-risk cornea transplantation. The study population was 18 years old or older with a high-risk transplant (two or more clock hours of cornea vascularization or a previous failed graft or a graft needed because of herpes simplex keratitis). A comprehensive search strategy was performed with the help of an information specialist and content experts from ophthalmology. All study designs were accepted for assessment. Level 1 and level 2 screening was performed by two reviewers followed by data abstraction. Forest plots were created whenever possible to synthesize treatment effects. Quality assessment was done with a Downs and Blacks score. From 1,150 articles, 29 were ultimately used for data abstraction. The odds ratios (ORs) for clear graft survival in cyclosporine and controls were 2.43 (95% CI: 1.00 - 5.88) and 3.64 (95% CI: 1.48 - 8.91) for rejection free episodes. Mycophenolate mofetil (MMF) significantly improved the rejection free graft survival rates at 1 year (OR: 4.05, 95% CI: 1.83 - 8.96). The overall results suggested that both systemic cyclosporine and MMF improved 1-year rejection free graft survival in high-risk keratoplasty. Cyclosporine also significantly improved clear graft survival rates at 1 year; however, there were insufficient data to analyze the same in the MMF group. Higher quality studies are needed to understand this issue better.

Immediately sequential bilateral cataract surgery: a cost-effective procedure.

OBJECTIVE: The objective of this project was to perform a cost-effectiveness analysis (CEA) of immediately sequential bilateral cataract surgery (ISBCS) versus delayed sequential bilateral cataract surgery (DSBCS) to determine whether ISBCS represents an appropriate, cost-effective way to rapidly rehabilitate a patient's visual impairment. DESIGN: A systematic review followed by a primary economic analysis with computer-based econometric modeling. PARTICIPANTS: Not applicable. METHODS: We constructed a decision analytic model from the perspective of the public third-party payer (i.e., the Ministry of Health) to conduct a CEA of both surgeries, ISBCS and DSBCS. Cost data consisted of the costs of the surgery, intravitreal injections, medications, and drops, all of which were obtained from a comprehensive literature search and from records at St. Joseph's Hospital, London, Ont. The effectiveness was measured by the utility values associated with visual acuity in the better seeing eye. RESULTS: ISBCS resulted in an incremental effectiveness of 0.08 utility at an incremental cost of $1607. Discounting the quality-adjusted life-years (QALYs) gained by an annual interest rate of 3% resulted in 0.932 QALYs gained. The cost-effectiveness of ISBCS was calculated to be $1431 per QALY gained. A 1-way sensitivity analysis was performed by varying costs, utility values, probabilities, and discounting rates. This analysis varied the incremental cost-effectiveness ratio but did not change the conclusion. CONCLUSIONS: Health economics assessment showed that, compared with DSBCS, ISBCS is a cost-effective procedure. This finding will be highly useful to policy-makers, decision-makers, clinicians, hospital administrators, and payers in making cost-efficient decisions.