Prevalence of vitreoschisis-induced vitreous cortex remnants over the peripheral retinal surface in eyes undergoing vitrectomy for primary rhegmatogenous retinal detachment.

PURPOSE: Unremoved vitreoschisis-induced vitreous cortex remnants over the peripheral retinal surface posterior to the vitreous base (pVCR) may increase the risk of surgical failure after primary rhegmatogenous retinal detachment (RRD) repair. The purpose of this study was to validate our previous findings on pVCR prevalence during vitrectomy for RRD and to examine their association with proliferative vitreoretinopathy (PVR) and surgical failure. METHODS: Prospective observational multisurgeon study of 100 eyes of 100 consecutive patients who underwent vitrectomy for RRD by one of four vitreoretinal surgeons. Collected data included detected pVCR and known PVR risk factors. Pooled analysis with our previous retrospective study (251 eyes of 251 patients) was also performed. RESULTS: Initial PVR (≥C) was present and removed in 6/100 (6%) patients, pVCR were detected in 36/100 (36%) patients, pVCR were removed in 30/36 (83%) patients with pVCR, and 4/36 (11%) patients with pVCR were high myopes (≤-6D). Six per cent (6/100) developed a retinal redetachment, of which 3/6 (50%) had initial PVR (≥C). Surgical failure rates in eyes with and without pVCR were 17% (6/36) and 0% (0/64), respectively. In eyes with pVCR and surgical failure, pVCR were not or not completely removed during the first surgery. Overall analysis showed that pVCR were statistically significantly associated with PVR. CONCLUSIONS: This study confirms our previous findings: a pVCR prevalence of around 35% and an association between pVCR, PVR formation and surgical failure in patients undergoing vitrectomy for RRD. More research is needed to determine which patients would benefit most from pVCR removal.

[Acute onset of floaters, even without flashes, is an urgent ophthalmic warning sign]. / Plotse toename van mouches volantes is een alarmsymptoom, ook zónder lichtflitsen.

Acute onset of floaters is most likely caused by a posterior vitreous detachment (PVD). A PVD can lead to a retinal tear and subsequently to a retinal detachment with permanent vision loss if left untreated. A patient who presents to a primary care physician with acute onset of floaters, in the absence flashes or visual field loss, is often referred to an ophthalmologist without urgency. In the current Dutch general practitioners standard, acute onset or increase of floaters, without flashes or visual loss, is not included as a reason for urgent referral to an ophthalmologist. Patients who present with acute onset of floaters without flashes have a 14-23% risk of having a retinal tear. Risk factors for developing a retinal tear are high myopia, trauma, cataract surgery, or a retinal tear or retinal detachment in the past medical or family history. Patients with acute onset of floaters should be triaged for urgent ophthalmologic assessment.

ANATOMICAL CHANGES ON SEQUENTIAL MULTIMODAL IMAGING IN PERIFOVEAL EXUDATIVE VASCULAR ANOMALOUS COMPLEX.

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.

Multimodal imaging comparison of perifoveal exudative vascular anomalous complex and resembling lesions.

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.

PROPHYLACTIC LASER TREATMENT TO DECREASE THE INCIDENCE OF RETINAL DETACHMENT IN FELLOW EYES OF IDIOPATHIC GIANT RETINAL TEARS.

PURPOSE: To evaluate the effectiveness of prophylactic 360° laser treatment in the fellow eye of patients with unilateral idiopathic giant retinal tear (GRT) to prevent the occurrence of a (macula-off) retinal detachment. METHODS: We conducted a retrospective, nonrandomized case-control study. Clinical data of consecutive patients, undergoing surgery for idiopathic GRT, between 2003 and 2015 were analyzed. The data collected included GRT, retinal detachment, and RTs in the fellow eye. RESULTS: We included 129 patients who underwent surgery for an idiopathic GRT, with a mean follow-up period of 107 months. In the observation group, a retinal detachment developed in the fellow eye in 22/51 patients (43.1%), leading to a macula-off detachment in 9/51 patients (17.6%). By contrast, in the prophylactic 360° laser group, only 10/78 (12.8%) patients developed a retinal detachment, leading to a macula-off detachment in 1/78 patient (1.3%). This difference was statistically significant. CONCLUSION: This study suggests that prophylactic 360° laser treatment in the fellow eye of patients with an idiopathic GRT decreased the incidence of retinal detachment, lowering the high risk of visual loss due to a macula-off retinal detachment.

Complications Following Enucleations and Subsequent Oculoplastic Surgeries.

PURPOSE: To analyze the complications and subsequent type and frequency of oculoplastic surgeries after enucleation in adult patients. METHODS: The authors conducted a retrospective case note review of adult patients who underwent enucleation followed by placement of an alloplastic implant wrapped in donor sclera between 2001 and 2013. The data collected included patient demographics, surgical indication, implant size, postoperative complications, and subsequent oculoplastic surgical procedures. RESULTS: The authors included 186 patients who underwent enucleation during the study period. Malignancy was the leading cause for this operation (79.6%) followed by a blind painful eye (12.4%). Most postoperative complications were managed conservatively with an adjustment of the size of the ocular prosthesis. In most cases, the 20-mm and 22-mm implants were used, and implant size ranged from 16 to 22 mm. There was no correlation between implant size and complication rate. Twenty-six patients required subsequent surgery after enucleation (14%). In total, 9.7% (18 patients of 186) patients underwent eyelid surgery after enucleation, most frequently for blepharoptosis (7%). The interval between enucleation and eyelid surgeries was, on average, 1.9 years. Less frequently, surgery is needed for socket repair for anterior surface breakdown (1.6%), and the interval between enucleation and socket surgery was 0.9 years. CONCLUSIONS: The most frequent complications following enucleation were blepharoptosis and enophthalmos with a deep upper eyelid sulcus. About 15% of patients required subsequent oculoplastic procedures after, on average, 2 years, while surgery in the early postoperative phase was rarely indicated.

A Single- Versus Double-Layered Closure Technique in Anophthalmic Surgery.

PURPOSE: To compare the frequency of orbital implant exposure and extrusion following eye removal with a simplified closure technique, closing Tenon's capsule and conjunctiva in 1 layer versus the classic technique of closure in 2 separate layers. METHODS: The authors conducted a retrospective case note review of patients who underwent evisceration or enucleation treated by 1 surgeon between 2001 and 2013. Between 2001 and 2004, Tenon's capsule and conjunctiva were closed in separate layers; after 2004, a simplified 1-layer closure following eye removal was used. The primary outcome parameters were presence or absence of implant exposure or extrusion. RESULTS: One hundred fifty-seven patients who underwent evisceration and 172 patients who underwent enucleation were included. Following evisceration, 2.5% developed exposure or extrusion of the implant, this was 2.5% in the 1-layer closure technique and 2.7% in the 2-layer closure technique (p = 0.95). Following enucleation, 1.7% developed exposure or extrusion of the implant, this was 1.8% in the 1-layer closure technique and 1.7% in the 2-layer closure technique (p = 0.96). Overall implant exposure and extrusion was 2.1%, this was 2.2% in the 1-layer closure technique and 2.1% in the 2-layer closure technique (p = 0.96). CONCLUSIONS: 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.

A single- versus double-layered closure technique for full-thickness lower eyelid defects: a comparative study.

PURPOSE: To compare a simplified, single-layered closure technique with a double-layered closure technique in lower eyelid reconstruction following full-thickness pentagonal block excision. METHODS: We conducted a retrospective, non-randomized, interventional case-control study. Clinical data of consecutive patients treated with primary closure of a full-thickness lower eyelid defect between 2011 and 2014 were analysed. In group A, the defect was closed in one layer, using non-absorbable polypropylene sutures. In group B, the defect was closed in two layers, using absorbable polyglactin acid sutures. In both techniques, we rarely used a grey line suture to adjust the eyelid margin. We assessed notching, wound dehiscence and other complications, as reported at 2 months after surgery. RESULTS: We included 188 eyelids from 186 patients. In group A, we included 82 eyelids and in group B 106 eyelids. We noted no difference in notching (p = 0.96) whilst wound dehiscence had not occurred in either group. Subcutaneous granuloma formation had been noted in 0 cases in group A, versus 4 in group B (p = 0.08). Mild redness of the scar was seen in 2 cases in group A, versus 5 in group B (p = 0.41). A grey line suture was placed in 6 cases in group A (7.3%), versus 4 cases in group B (3.8%; p = 0.28). CONCLUSION: Both single- and double-layered closure techniques are safe and effective methods for primary closure of full-thickness lower eyelid defects. In both techniques, a grey line suture was rarely required to adjust the eyelid margin.

Percutaneous Aponeurotomy and Lipofilling (PALF): A Regenerative Approach to Dupuytren Contracture.

Dupuytren disease is a progressive fibroproliferative disorder, which leads to flexion contractures of the digits. A minimally invasive technique consisting of an extensive percutaneous aponeurotomy of the cord with a needle combined with lipofilling is presented. The selective cutting of the cords under continuous tension disintegrates the cords while sparing the looser neurovascular bundles. Subsequently, lipoaspirate is injected subcutaneously. The authors' prospective results show a significantly shorter recovery time and less overall complications in this technique when compared with open surgery, while no significant difference was observed in the extent of immediate contracture correction and in the recurrence rate at 1 year follow-up.

Adipose-derived stem cells inhibit the contractile myofibroblast in Dupuytren's disease.

BACKGROUND: In an attempt to provide minimally invasive treatment for Dupuytren's disease, percutaneous disruption of the affected tissue followed by lipografting is being tested. Contractile myofibroblasts drive this fibroproliferative disorder, whereas stem cells have recently been implicated in preventing fibrosis. Therefore, the authors tested the role of stem cells in modulating myofibroblast activity in Dupuytren's disease. METHODS: The authors compared the effect of co-culturing Dupuytren's myofibroblasts with either adipose-derived or bone-marrow-derived stem cells on isometric force contraction and associated levels of α-smooth muscle actin mRNA and protein expression. The authors also tested the effect of these stem cells on Dupuytren's myofibroblast proliferation and assessed whether this was mediated by cell-to-cell contact or by a paracrine mechanism. RESULTS: Addition of adipose-derived stem cells to Dupuytren's myofibroblasts reduced the contraction of the latter, with a corresponding reduction of α-smooth muscle actin protein expression, probably through a dilution effect. In contrast, bone marrow-derived stem cells increased myofibroblast contractility. In addition, adipose-derived stem cells inhibit myofibroblast proliferation and mediate these effects by soluble factors, influenced by cell-to-cell contact-dependent signaling. CONCLUSION: 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.

Isometric contraction of Dupuytren's myofibroblasts is inhibited by blocking intercellular junctions.

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.

Unraveling the signaling pathways promoting fibrosis in Dupuytren's disease reveals TNF as a therapeutic target.

Dupuytren's disease is a very common progressive fibrosis of the palm leading to flexion deformities of the digits that impair hand function. The cell responsible for development of the disease is the myofibroblast. There is currently no treatment for early disease or for preventing recurrence following surgical excision of affected tissue in advanced disease. Therefore, we sought to unravel the signaling pathways leading to the development of myofibroblasts in Dupuytren's disease. We characterized the cells present in Dupuytren's tissue and found significant numbers of immune cells, including classically activated macrophages. High levels of proinflammatory cytokines were also detected in tissue from Dupuytren's patients. We compared the effects of these cytokines on contraction and profibrotic signaling pathways in fibroblasts from the palmar and nonpalmar dermis of Dupuytren's patients and palmar fibroblasts from non-Dupuytren's patients. Exogenous addition of TNF, but not other cytokines, including IL-6 and IL-1ß, promoted differentiation into specifically of palmar dermal fibroblasts from Dupuytren's patients in to myofibroblasts. We also demonstrated that TNF acts via the Wnt signaling pathway to drive contraction and profibrotic signaling in these cells. Finally, we examined the effects of targeted cytokine inhibition. Neutralizing antibodies to TNF inhibited the contractile activity of myofibroblasts derived from Dupuytren's patients, reduced their expression of α-smooth muscle actin, and mediated disassembly of the contractile apparatus. Therefore, we showed that localized inflammation in Dupuytren's disease contributes to the development and progression of this fibroproliferative disorder and identified TNF as a therapeutic target to down-regulate myofibroblast differentiation and activity.

The mechanical environment in Dupuytren's contracture determines cell contractility and associated MMP-mediated matrix remodeling.

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 pre-determined 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.