Hemiretinal vein occlusion 12-month outcomes are unique with vascular endothelial growth factor inhibitors: data from the Fight Retinal Blindness! Registry

BACKGROUND/AIMS To describe baseline characteristics and 12-month outcomes with vascular endothelial growth factor (VEGF) inhibitors of treatment-naïve hemiretinal vein occlusion (HRVO) compared with branch (BRVO) and central (CRVO) variants in routine clinical care. METHODS A database observational study recruited 79 HRVO eyes, 590 BRVO eyes and 344 CRVO eyes that initiated therapy over 10 years. The primary outcome was mean change in visual acuity (VA-letters read on a logarithm of minimal angle of resolution chart) at 12 months. Secondary outcomes included mean change in central subfield thickness (CST), injections and visits. RESULTS At baseline, mean VA in HRVO (53.8) was similar to CRVO (51.9; p=0.40) but lower than BRVO (59.4; p=0.009). HRVO eyes improved to match BRVO eyes from soon after treatment started through 12 months. Mean change in VA was greater in HRVO (+16.4) than both BRVO (+11.4; p=0.006) and CRVO (+8.5; p<0.001). Mean change in CST in HRVO (-231 µm) was similar to CRVO (-259 µm; p=0.33) but greater than BRVO eyes (-151 µm; p=0.003). The groups had similar median burdens of eight injections and nine visits. CONCLUSIONS HRVO generally experienced the greatest mean change in VA of the three types of RVO when treated with VEGF inhibitors, ending with similar 12-month VA and CST to BRVO despite starting closer to CRVO. Inclusion of HRVO in BRVO or CRVO cohorts of clinical trials would be expected to proportionally inflate and skew the visual and anatomic outcomes

Remodeling of the adult human vitreous and vitreoretinal interface: a dynamic process

The vitreous body (or vitreous) of the human eye is an almost acellular, transparent loose-meshed connective tissue consisting mainly of water (99%) and of just 0.1% macromolecules, such as glycosaminoglycans (e.g. hyaluronan), proteoglycans, glycoproteins (such as opticin), collagens, and noncollagenous structural proteins (e.g. fibrillin). The most important macromolecules are the collagens, which form a network of heterotypic fibrils (types 11, V, IX, and XI) and presumably maintain the gel structure. Collagen types present in the vitreous are types II, V, VI, IX, and XI. Vitreous structure has been studied in some detail, but there is no absolute distinctness in anatomy in the literature, which might be explained by (i) the high water content, (ii) the use of different preservation methods, and (iii) the variable visualization techniques. The presence and course of intravitreal structures (e.g. lamellae, channels, and cisterns) are still discussed

In vitro phagocytosis of collagens by immortalised human retinal Muller cells

Purpose: This study is a first step to investigate phagocytosis of collagens by human retinal Muller cells, since Muller cells could be involved in remodelling of the vitreous and vitreoretinal interface in the human eye. Methods: Muller cells in culture were exposed to 2.0 mu m fluorescent latex beads coated with BSA and human types I, II, and IV collagen and to non-coated beads for 2, 12, 24, and 48 h. To influence phagocytosis, cytochalasin B and anti-integrin subunits (alpha 1, alpha 2, and beta 1) were added to the cells. Phagocytosis was evaluated by flow cytometry, transmission electron microscopy (TEM) and confocal microscopy. Results: Muller cells preferred to phagocytose beads coated with type II collagen compared with type IV collagen-, BSA- and non-coated beads. Phagocytosis of type I collagen- coated beads was intermediate. TEM and confocal microscopic evaluation confirmed phagocytosis of the beads. No significant differences were observed in phagocytosis of type II collagen- coated beads in the case of addition of cytochalasin B and anti-integrin subunits. Immunohistochemical analyses revealed that Muller cells were positive, under all tested circumstances, for vimentin and CRALBP. Less than 5% of the cells tested were GFAP positive. Conclusions: Our observations demonstrate that human Muller cells in culture prefer to phagocytose type II collagen. In contrast, the phagocytosis of type IV collagen is comparable with the control coatings. We speculate that the relatively limited collagen phagocytosis by Muller cells supports a possible role for Muller cells in the slow process of vitreoretinal remodelling in adult human eyes

Longer treatment intervals are associated with reduced treatment persistence in neovascular age related macular degeneration

AIMS To test the hypothesis that patients treated for neovascular age related macular degeneration (nAMD) with longer treatment intervals are more likely to persist with treatment. METHODS Data were obtained from the prospectively-defined Fight Retinal Blindness! registry. Treatment interval at 2 years was stratified based on the mean treatment interval over the three visits prior to and including the 2-year visit. Rates of non-persistence to follow-up were assessed from 2 to 5 years. RESULTS Data from 1538 eyes were included. The overall rate of non-persistence was 51% at 5 years. Patients on longer treatment intervals (12-weeks) at 2 years were found to be less persistent to long-term follow-up. These eyes were found to have fewer active disease visits in the first 2 years (40%) than eyes treated at 4-weekly intervals (66%, p  12-week intervals vs. 4-week intervals, respectively, P = 0.002) and older patients (HR [95% CI]: 1.03 [1.02, 1.04], p < 0.001) were at higher risk of non-persistence. CONCLUSIONS We found that patients on longer treatment intervals at 2 years were more likely to be non-persistent with treatment in later years. Reinforcing the need for ongoing treatment is important for patients on longer intervals who may feel complacent or that treatment is no longer effective, particularly if newer, longer lasting agents become widely available