Significance Fibrosis, a hallmark of many clinical disorders, occurs because of uncontrolled myofibroblast activity. We studied Dupuytren's disease, a common hereditable fibrotic condition that causes the fingers to irreversibly curl toward the palm. We found that freshly isolated tissue from Dupuytren's patients contained macrophages and released proinflammatory protein mediators (cytokines). Of the cytokines, only TNF selectively converted normal fibroblasts from the palm of patients with Dupuytren's disease into myofibroblasts via activation of the Wnt signaling pathway. Conversely, blockade of TNF resulted in reversal of the myofibroblast phenotype. Therefore, TNF inhibition may prevent progression or recurrence of Dupuytren's disease.

Adipose-derived stem cells inhibit the contractile myofibroblast in Dupuytren's disease, and these findings lend support to the potential benefit of lipografting in conjunction with aponeurotomy as a novel strategy for the treatment of Dupuytren's disease.

Myofibroblasts (MFs) are responsible for both physiological wound and scar contraction. However, it is not known whether these cells act individually to contract the surrounding matrix or whether they behave in a coordinated manner. Therefore, we studied intercellular junctions of primary human MFs derived from patients with Dupuytren's disease, a fibrotic disorder of the dermis and subdermal tissues of the palm. The cells were maintained in anchored three-dimensional collagen lattices to closely mimic conditions in vivo. We found that selective blockade of adherens, mechanosensitive, or gap junctions effectively inhibited contraction of the collagen matrices and downregulated the MF phenotype. Our data indicate that MFs in part function as a coordinated cellular syncytium, and disruption of intercellular communication may provide a therapeutic target in diseases characterized by an overabundance of these contractile cells.

Flashes and floaters are the hallmark symptoms of a posterior vitreous detachment (PVD) which itself is related to an increased risk of the development of retinal tears, retinal detachment and vitreous haemorrhage. The aim of this study is to assess the associations between different symptoms related to PVD and the risk of developing retinal tears. A systematic review of articles written in English, using MEDLINE, Embase (via Embase.com) and the Cochrane Controlled Trials Register (1996–2017) was conducted. Search terms included five elements: PVD, retinal tears, retinal detachment, floaters and flashes. Independent extraction of articles was conducted by two authors using predefined data fields, including study quality indicators. Thirteen studies fulfilled the selection criteria. Analysis of pooled data revealed that presence of isolated flashes was associated with the development of retinal tears in 5.3% of symptomatic eyes [mean 2.9 eyes; 95% CI (2.1, 5.7)].Conversely, floaters alone had a stronger association with retinal tears (16.5% of eyes), as compared to flashes. The association to retinal tears was even greater for those patients reporting both flashes and floaters [mean 17.8 eyes (20.0%); 95% CI (17.4, 18.1)]. Retinal and/or vitreous haemorrhage was also associated with the presence and later development of retinal tears [mean 12.5 eyes (30.0%); 95% CI (11.7, 13.9)]. Patients with more than 10 floaters or a cloud in their vision had a high risk of developing retinal tears (OR19.8, p‐value 0.032). In the setting of a PVD, the onset of flashes and floaters, and the presence of retinal and/or vitreous haemorrhage are risk factors for the development of retinal tears. The association is greater when both symptoms are present, and even greater when the patient reports more than 10 floaters, a curtain or a cloud and/or there is a positive finding of a vitreous or retinal haemorrhage. This study supports the necessity of an immediate examination of patients presenting with symptoms related to a PVD, and a follow‐up examination might be prudent in a subgroup of these patients.

Purpose: To report a series of 21 patients with perifoveal exudative vascular anomalous complex (PEVAC) and to investigate the anatomical changes over time. Methods: We conducted a retrospective study. Clinical data of consecutive patients, presenting at the Rotterdam Eye Hospital between 2014 and 2019, were analyzed. The data collected included best-corrected visual acuity, fundus photography, optical coherence tomography (OCT), OCT-angiography, fluorescence angiography, and indocyanine green angiography. Results: We included 21 patients with a PEVAC lesion with a mean follow-up of 24.3 ± 13.8 months (range, 9–46 months). Patients with PEVAC were on average 75.3 ± 11.1 years (range, 53–90 years). The large perifoveal vascular aneurysmal abnormality was associated with small retinal hemorrhages in six patients and hard exudates in three patients. The PEVAC lesion was associated with intraretinal cystic spaces on OCT in 15 patients. Twelve of 21 patients showed no changes in cystic spaces on OCT during follow-up: 9 patients had stable cystic spaces and 3 patients had no cystic spaces. In contrast, in 9 of 21 patients, we observed changes in cystic spaces on OCT during follow-up. In two patients, cystic spaces appeared during follow-up, and in seven patients, there was a spontaneous resolution of cystic spaces. In three of these seven patients, the PEVAC lesion completely disappeared. Two patients, with stable intraretinal cystic spaces on OCT, were treated with intravitreal injections of anti–vascular endothelial growth factor without improvement. Conclusion: Perifoveal exudative vascular anomalous complex is an idiopathic perifoveal retinal vascular abnormality that is associated with intraretinal cystic spaces. These intraretinal cystic spaces associated with a PEVAC lesion, and even the PEVAC lesion itself, can have a spontaneous resolution over time.

Matrix metalloproteinases (MMPs) are expressed in Dupuytren's contracture and play a role in matrix remodeling. We tested the role of tension on contractility and MMP expression in Dupuytren's nodule and cord cells. Cells were subjected to predetermined loading patterns of known repeatable magnitudes (static load, unloading, and overloading) and tested for MMP gene expression (MMP-1, -2, -9, -13, and TIMP-1, -2) and force generation using a tension-culture force monitor. Matrix remodeling was assessed by addition of cytochalasin D and residual matrix tension was quantified. Nodule compared to cord and control cells demonstrate greater force generation and remodeling (p < 0.05). Nodule cells subjected to a reduced load and overloading led to threefold increase of MMP-1, -2, and -9 compared to static load, whilst cord and control cells only showed a twofold increase of MMP-9. Nodule cells subjected to overloading showed a twofold increase in TIMP-2 expression, whilst cord and control cells showed a twofold increase in TIMP-1 expression. Nodule cells differ from cord cells by increased force generation in response to changes in the mechanical environment and related MMP/TIMP-mediated matrix remodeling. In turn this may lead to permanent matrix shortening and digital contracture. Interventional therapies should be aimed at nodule cells to prevent contraction and subsequent permanent matrix remodeling. ß

No difference was found in the frequency of spheric acrylic implant exposure or extrusion in patients who underwent eye removal with single-layer closure of Tenon's capsule and conjunctiva compared with patients treated with separate closure of these layers.

Purpose Perifoveal exudative vascular anomalous complex (PEVAC) was initially described as an isolated aneurysmal lesion in healthy eyes. Similar aneurysmal abnormalities may occur in association with retinal vascular diseases such as diabetic retinopathy or retinal vein occlusions (PEVAC‐resembling). The aim of this study was to compare several imaging characteristics of PEVAC and PEVAC‐resembling lesions. Methods Ten eyes with a PEVAC and 27 eyes with a PEVAC‐resembling lesion were included in this cross‐sectional study. They were all imaged with optical coherence tomography (OCT), OCT angiography (OCT‐A) and colour fundus photography (CFP). Several clinical, morphological and vascular characteristics were assessed and compared between both PEVAC types. Results All PEVAC lesions were unilateral, while PEVAC‐resembling lesions appeared bilateral in 23% of patients (p > 0.05). Unilateral multifocal PEVAC‐resembling lesions were more frequently observed (56%) than unilateral multifocal PEVAC lesions (10%, p < 0.01). Furthermore, 90% of the PEVAC lesions were located within 500 µm from the centre of the fovea, while this was only true for 56% of the PEVAC‐resembling lesions (p > 0.05). No notable differences were observed in other studied characteristics. Conclusions The clinical, morphological and vascular features of PEVAC and PEVAC‐resembling lesions are similar based on multimodal imaging. Given the bilaterality and multifocality seen in PEVAC‐resembling lesions, an underlying retinal vascular disease may stimulate the quantity of aneurysmal abnormalities. Due to the similarities with PEVAC‐resembling lesions, PEVAC may also be considered a microangiopathy but with an unknown origin.