Bernd Junker

Efficacy and safety of intravitreal therapy in macular edema due to branch and central retinal vein occlusion: a systematic review.

Background Intravitreal agents have replaced observation in macular edema in central (CRVO) and grid laser photocoagulation in branch retinal vein occlusion (BRVO). We conducted a systematic review to evaluate efficacy and safety outcomes of intravitreal therapies for macular edema in CRVO and BRVO. Methods And Findings: MEDLINE, Embase, and the Cochrane Library were systematically searched for RCTs with no limitations of language and year of publication. 11 RCTs investigating anti-VEGF agents (ranibizumab, bevacizumab, aflibercept) and steroids (triamcinolone, dexamethasone implant) with a minimum follow-up of 1 year were evaluated. Efficacy: CRVO Greatest gain in visual acuity after 12 months was observed both under aflibercept 2 mg: +16.2 letters (8.5 injections), and under bevacizumab 1.25 mg: +16.1 letters (8 injections). Ranibizumab 0.5 mg improved vision by +13.9 letters (8.8 injections). Triamcinolone 1 mg and 4 mg stabilized visual acuity at a lower injection frequency (-1.2 letters, 2 injections). BRVO Ranibizumab 0.5 mg resulted in a visual acuity gain of +18.3 letters (8.4 injections). The effect of dexamethasone implant was transient after 1.9 implants in both indications. Safety Serious ocular adverse events were rare, e.g., endophthalmitis occurred in 0.0-0.9%. Major differences were found in an indirect comparison between steroids and anti-VEGF agents for cataract progression (19.8-35.0% vs. 0.9-7.0%) and in required treatment of increased intraocular pressure (7.0-41.0% vs. none). No major differences were identified in systemic adverse events. Conclusions Anti-VEGF agents result in a promising gain of visual acuity, but require a high injection frequency. Dexamethasone implant might be an alternative, but comparison is impaired as the effect is temporary and it has not yet been tested in PRN regimen. The ocular risk profile seems to be favorable for anti-VEGF agents in comparison to steroids. Because comparative data from head-to-head trials are missing currently, clinicians and patients should carefully weigh the benefit-harm ratio.

Levels of VEGF but not VEGF165b are Increased in the Vitreous of Patients With Retinal Vein Occlusion

PURPOSE To determine the concentration of the pro-angiogenic vascular endothelial growth factor VEGF(165) (VEGF) and the anti-angiogenic VEGF(165b) in vitreous samples of patients with branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) in comparison to patients without retinal occlusive disease. DESIGN Experimental laboratory investigation. METHODS Vitreous samples were collected from patients undergoing surgery for arteriovenous dissection after BRVO, radial optic neurotomy after CRVO in the occlusion group, or macular pucker or macular hole in the control group. Concentrations of VEGF and VEGF(165b) were determined by ELISA and an ELISA-type antibody microarray. RESULTS Average vitreal concentration of VEGF was 8.6 ng/mL in the CRVO group and 2.0 ng/mL in the BRVO group as compared to 0.26 ng/mL in the control group. Average vitreal concentration of VEGF(165b) was 27 pg/mL in the CRVO group, 42 pg/mL in the BRVO group, and 49 pg/mL in the control group. In patients with CRVO and BRVO, the angiogenic balance was shifted towards angiogenic stimulation. CONCLUSION The severity of RVO from BRVO to CRVO correlates with an increase of VEGF and the decrease of VEGF(165b), indicating a pro-angiogenic shift. Altering the ratio of VEGF(165b)/VEGF(165) might be a feasible approach for treating retinal occlusive diseases.

Vitreal levels of erythropoietin are increased in patients with retinal vein occlusion and correlate with vitreal VEGF and the extent of macular edema.

Purpose: This study compares vitreal levels of erythropoietin (EPO) in patients with retinal vein occlusion (RVO) with control subjects. In addition, it investigates different RVO disease parameters (time of vein occlusion, patient age, vitreal vascular endothelial growth factor (VEGF) levels, and extent of central macular edema) for possible correlations with vitreal EPO levels. Methods: Serum and vitreal EPO were measured from 6 patients with branch retinal vein occlusion, 6 patients with central retinal vein occlusion, and 12 control subjects (10 macular puckers and 2 macular holes). Results: Serum EPO levels (9.8 ± 4.9 mU/mL) did not differ between the RVO and control groups and were significantly lower than vitreal EPO levels in all groups. Vitreal EPO was elevated both in branch RVO (91 ± 59 mU/mL) and central RVO (182 ± 70 mU/mL) compared with controls (35 ± 24 mU/mL). Increased vitreal EPO correlated with higher vitreal VEGF (r = 0.64, P = 0.0008) and more pronounced central macular edema (r = 0.66, P = 0.001). Conclusion: The results from this study indicate that EPO is locally expressed in the retina and that it is upregulated together with VEGF in RVO eyes. Because of its role both in neuroprotection and angiogenesis, ocular EPO might represent an interesting target to investigate in patients with RVO, especially in light of the current anti-VEGF treatments.

Ranibizumab for Branch Retinal Vein Occlusion Associated Macular Edema Study (RABAMES): six-month results of a prospective randomized clinical trial

To compare standard‐of‐care grid laser photocoagulation versus intravitreal ranibizumab (IVR) versus a combination of both in the treatment of chronic (>3 months) macular oedema secondary to branch retinal vein occlusion.

Intra- and postoperative risks and complications of small-gauge (23-G) versus conventional (20-G) vitrectomy for macular surgery

Purpose To compare the complication spectrum and rate of 23-G and 20-G vitrectomy for macular surgery. Methods This was a retrospective comparative analysis of 20-G and 23-G vitrectomy (introduced in 2007) for macular surgery due to macular pucker or macular hole performed between 2006 and 2010 in 61 and 59 eyes, respectively, by 2 experienced surgeons and 2 trainees. We assessed the adjusted hazard ratio for vitrectomy 23-G vs 20-G with a Cox proportional hazard model. We counted retinal detachment, vitreous hemorrhage, endophthalmitis (as early postoperative complications), or cataract progression (as late postoperative complication) as endpoint. We adjusted for indication, surgeon, retinopexy method, and the endotamponade. Results Follow-up averaged 712 days. Median time to first event was 385 days in the 23-G group and 342 days in the 20-G group. Cox proportional hazard analysis showed no significant difference between vitrectomy 23-G vs 20-G with regard to postoperative complications (hazard ratio 0.79, 95% confidence interval 0.41-1.52). The other covariates did not exert a statistically significant effect on the risk of adverse events. Looking at individual complications, retinal detachment was exclusively found after 20-G. Conclusions In this homogenous large cohort, we did not find a statistically significant difference in rates of complications between 23-G and 20-G vitrectomy techniques for macular surgery. Trainees performed equally well as experienced surgeons.

Diffuse Unilateral Subacute Neuroretinitis Caused by Ancylostoma Hookworm

Diffuse unilateral subacute neuroretinitis is an ocular infectious disease caused by several distinct nematodes. Definite identification of the involved nematodes is rarely achieved. We report on the molecular-based genetic identification of an Ancylostoma ceylanicum hookworm implicated in a case of diffuse unilateral subacute neuroretinitis in a child.

Switch of Intravitreal Therapy for Macular Edema Secondary to Retinal Vein Occlusion from Anti-VEGF to Dexamethasone Implant and Vice Versa

Purpose To evaluate the anatomical and functional outcome of intravitreal dexamethasone implant for macular edema secondary to central (C) or branch (B) retinal vein occlusion (RVO) in patients with persistent macular edema (ME) refractory to intravitreal antivascular endothelial growth factor (VEGF) treatment compared to treatment naïve patients and to dexamethasone-refractory eyes switched to anti-VEGF. Methods Retrospective, observational study including 30 eyes previously treated with anti-VEGF (8 CRVO, 22 BRVO, mean age 69 ± 10 yrs), compared to 11 treatment naïve eyes (6 CRVO, 5 BRVO, 73 ± 11 yrs) and compared to dexamethasone nonresponders (2 CRVO, 4 BRVO, 69 ± 12). Outcome parameters were change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) measured by spectral-domain optical coherence tomography. Results Mean BCVA improvement after switch to dexamethasone implant was 4 letters (p = 0.08), and treatment naïve eyes gained 10 letters (p = 0.66), while we noted no change in eyes after switch to anti-VEGF (p = 0.74). Median CFT decrease was most pronounced in treatment naïve patients (−437 μm, p = 0.002) compared to anti-VEGF refractory eyes (−170 μm, p = 0.003) and dexamethasone-refractory eyes (−157, p = 0.31). Conclusions Dexamethasone significantly reduced ME secondary to RVO refractory to anti-VEGF. Functional gain was limited compared to treatment naïve eyes, probably due to worse BCVA and CFT at baseline in treatment naïve eyes.

Intraoperative optical coherence tomography and ab interno trabecular meshwork surgery with the Trabectome

Importance This study is the first description of the use of the intraoperative optical coherence tomography (iOCT) for trabecular meshwork surgery with the Trabectome in a regular clinical setting. Background The aim of this study is to evaluate intraoperatively the immediate success of ab interno trabeculotomy with the Trabectome defined as a removal of the trabecular meshwork. Design This is a retrospective clinical study performed in the University Eye Hospital, Medical School Hannover. Participants A total of nine consecutive Caucasian patients suffering from primary open angle glaucoma, pigment dispersion glaucoma, or pseudoexfoliation glaucoma took part in the study. Methods All patients underwent ab interno trabeculotomy surgery with the Trabectome using a commercially available iOCT to visualize the anterior chamber angle (ACA) before and after the procedure. The visualization was done using a modified Swan-Jacobs lens (all nine patients) or without lens (view from above, five patients). Main outcome measures The main outcome of this study is the success of visualization of the ACA on iOCT, especially the postprocedural visualization of the wound gap after removal of the trabecular meshwork. Results Using the view from above, the ACA could be visualized before and after the procedure in only two of the five cases. Using the modified Swan-Jacobs lens, the ACA could be visualized before the procedure and the trabecular meshwork opening after the procedure in all nine patients. Conclusion The iOCT can be used to objectify the immediate success of the surgical procedure, ie, the removal of the trabecular meshwork, of ab interno trabeculotomy with the Trabectome. The procedure itself cannot be captured sufficiently via iOCT.

Retinal Vein Occlusion

Vitreous levels of vascular endothelial growth factor (VEGF) are increased in retinal vein occlusion. Visual impairment occurs secondary to macular edema which is enforced and maintained by VEGF. Intravitreal corticosteroids such as triamcinolone acetonide and dexamethasone implant as well as VEGF-inhibitors ranibizumab, bevacizumab, pegaptanib, and aflibercept target the overexpression of VEGF, reduce macular edema, and lead to significant improvement of vision.