Age-related changes in vitreous molecular and anatomic morphology begin early in life and involve two major processes: vitreous liquefaction and weakening of vitreo-retinal adhesion. An imbalance in these two processes results in anomalous posterior vitreous detachment (PVD), which comprises, among other conditions, vitreo-macular adhesion (VMA) and traction (VMT). VMA is more common in patients with neovascular age-related macular degeneration (nAMD) than age-matched control patients, with the site of posterior vitreous adherence to the inner retina correlating with location of neovascular complexes. The pernicious effects of an attached posterior vitreous on age-related macular degeneration (AMD) progression involve mechanical forces, enhanced fluid influx and inflammation in and between the retinal layers, hypoxia leading to an accumulation of vascular endothelial growth factor (VEGF) and other stimulatory cytokines, and probably an infiltration of hyalocytes. It has been shown that vitrectomy not only mitigates progression to end-stage AMD, but existing choroidal neovascularization regresses after surgery. Thus, surgical PVD induction during vitrectomy or by pharmacologic vitreolysis may be considered in non-responders to anti-VEGF treatment with concomitant VMA.
UNASSIGNED: Altersbedingte Veränderungen der molekularen und anatomischen Morphologie des Glaskörpers beginnen schon früh im Leben und umfassen 2 Hauptprozesse: die Glaskörperverflüssigung und die Schwächung der vitreoretinalen Adhäsion. Ein Ungleichgewicht zwischen diesen beiden Prozessen führt zu einer anomalen hinteren Glaskörperabhebung (HGA), die unter anderem die vitreomakuläre Adhäsion (VMA) und Traktion (VMT) umfasst. VMA tritt bei Patienten mit neovaskulärer altersabhängiger Makuladegeneration (nAMD) häufiger auf als bei altersgleichen Kontrollpatienten, wobei die Stelle, an der der hintere Glaskörper an der inneren Netzhaut haftet, mit der Lage des neovaskulären Komplexes korreliert. Die schädlichen Auswirkungen eines anhaftenden hinteren Glaskörpers auf die Progression der altersabhängigen Makuladegeneration (AMD) umfassen mechanische Kräfte, einen verstärkten Flüssigkeitseinstrom und Inflammation in und zwischen den Netzhautschichten, Hypoxie, die zu einer Akkumulation von „vascular endothelial growth factor“ (VEGF) und anderen stimulierenden Zytokinen führt, und wahrscheinlich auch eine Infiltration von Hyalozyten. Es hat sich gezeigt, dass eine Vitrektomie nicht nur das Fortschreiten der AMD im Endstadium aufhält, sondern auch dass sich bestehende chorioidale Neovaskularisationen nach der Operation zurückbilden. Daher kann eine chirurgische HGA-Induktion im Rahmen der Vitrektomie oder durch pharmakologische Vitreolyse bei Nichtansprechen auf die Anti-VEGF-Behandlung und gleichzeitig vorliegender VMA in Betracht gezogen werden.

OBJECTIVE: To evaluate the effect of vitreomacular interface (VMI) configuration on treatment outcomes after intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) using optical coherence tomography (OCT).
METHODS: A systematic literature search was performed on PubMed, Embase, web of science and clinicaltrials.gov. The primary outcome parameters were central macular thickness (CMT), best-corrected visual acuity (BCVA) and mean injection numbers. We performed this meta-analysis by Review Manager (RevMan) 5.4.1.
RESULTS: The impact of epiretinal membrane (ERM), vitreomacular traction (VMT) and vitreomacular adhesion (VMA) on the treatment outcomes were analyzed separately. 9 clinical studies involving 699 eyes were eligible for the meta-analysis for evaluating the effect of ERM/VMT on efficacy. And 7 studies with 610 eyes were included to access whether VMA affected the response to anti-VEGF therapy in patients with DME. The ERM/VMT group had poorer CMT reductions than the control group at 1 month ([MD] 52.91 mm, P<0.00001), while no significant difference at 3 months ([MD] 43.95 mm, P = 0.22) and over 12 months ([MD] 30.51 mm, P = 0.45). No statistically significant difference in the mean BCVA change at 1 month ([MD] -0.03 Log MAR, P = 0.79), whereas ERM/VMT group had poor visual acuity gains at 3 months ([MD] 0.08 Log MAR, P = 0.003), and a tendency of poor vision improvement over 12 months follow-up ([MD] 0.07 Log MAR, P = 0.11). There was no significant difference in the visual and anatomical results over 3 months in DME patients with or without VMA ([MD] -21.92 mm, P = 0.09; [MD] 1.79 letters, P = 0.22). Besides, VMI configuration was not found to affect mean injection numbers.
CONCLUSIONS: The limited evidence suggested that ERM/VMT was associated with worse CMT reduction at 1 month, poor BCVA gain at 3 months and a tendency of limited vision improvement over 12 months follow-up in DME patients treated with anti-VEGF agents. And VMA may not adversely affect the anatomic and functional outcomes. However, the results of this meta-analysis should be interpreted with caution because of the heterogeneity among study designs.

Purpose: Ocriplasmin (Jetrea TM) is a FDA approved recombinant enzyme utilized in the treatment of vitreomacular adhesion (VMA). This is a recombinant C-terminal fragment of human plasmin produced using yeast Pichia pastoris. Since ocriplasmin does not contain any Oor N-glycosylation or some other post-translational modifications, bacterial expression systems such as Escherichia coli could be considered as an economical host for recombinant expression. In the present study, we aimed to evaluate the efficiency of E. coli expression system for highlevel expression of recombinant ocriplasmin. Methods: The gene coding for ocriplasmin was cloned and expressed in E. coli BL21. The bacterial cells were cultured on large scale and the expressed recombinant protein was purified using Ni-NTA chromatography. Refolding of denatured ocriplasmin to active enzyme was carried out by the stepwise removal of denaturant. The identity of recombinant ocriplasmin was confirmed using western blotting and ELISA assays. The presence of the active ocriplasmin was monitored by the hydrolytic activity assay against the chromogenic substrate S-2403. Results: The final yield of E. coli BL21-produced ocriplasmin was approximately 1 mg/mL which was greater than that of P. pastoris. Using western blotting and ELISA assay, the identity of recombinant ocriplasmin was confirmed. The hydrolysis of chromogenic substrate S-2403 verified the functional activity of E. coli produced ocriplasmin. Conclusion: The results of this study indicated that E. coli could be used for high level expression of ocriplasmin. Although the recombinant protein was expressed as inclusion body, the stepwise refolding leads to the biologically active proteins.