Anomalous Posterior Vitreous Detachment Research Articles

Hyalocytes-guardians of the vitreoretinal interface.

Originally discovered in the nineteenth century, hyalocytes are the resident macrophage cell population in the vitreous body. Despite this, a comprehensive understanding of their precise function and immunological significance has only recently emerged. In this article, we summarize recent in-depth investigations deciphering the critical role of hyalocytes in various aspects of vitreous physiology, such as the molecular biology and functions of hyalocytes during development, adult homeostasis, and disease. Hyalocytes are involved in fetal vitreous development, hyaloid vasculature regression, surveillance and metabolism of the vitreoretinal interface, synthesis and breakdown of vitreous components, and maintenance of vitreous transparency. While sharing certain resemblances with other myeloid cell populations such as retinal microglia, hyalocytes possess a distinct molecular signature and exhibit a gene expression profile tailored to the specific needs of their host tissue. In addition to inflammatory eye diseases such as uveitis, hyalocytes play important roles in conditions characterized by anomalous posterior vitreous detachment (PVD) and vitreoschisis. These can be hypercellular tractional vitreo-retinopathies, such as macular pucker, proliferative vitreo-retinopathy (PVR), and proliferative diabetic vitreo-retinopathy (PDVR), as well as paucicellular disorders such as vitreo-macular traction syndrome and macular holes. Notably, hyalocytes assume a significant role in the early pathophysiology of these disorders by promoting cell migration and proliferation, as well as subsequent membrane contraction, and vitreoretinal traction. Thus, early intervention targeting hyalocytes could potentially mitigate disease progression and prevent the development of proliferative vitreoretinal disorders altogether, by eliminating the involvement of vitreous and hyalocytes.

Role of vitreous in the pathogenesis of neovascular age-related macular degeneration

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.

Age-related changes in human vitreous

There are two main age-related changes that can occur in the vitreous body of healthy individuals throughout life: liquefaction (synchesis) and aggregation of collagen fibrils into dense bundles (syneresis). Progressive age-related degradation leads to posterior vitreous detachment (PVD). At present many classifications of PVD exist, in which authors relied either on the morphological features, or on the differences in pathogenesis before and after widespread use of OCT. The course of PVD can be either normal or anomalous. Physiological PVD induced by age-related vitreous changes progresses in specific stages. The review emphasizes that PVD can occur initially not only in the central zone of the retina, but also on the periphery with further spread to the posterior pole. Anomalous PVD can lead to various negative effects on the retina, as well as on the vitreous as a result of traction in the area of vitreoretinal interface.

Müller cells and astrocytes in tractional macular disorders.

Tractional deformations of the fovea mainly arise from an anomalous posterior vitreous detachment and contraction of epiretinal membranes, and also occur in eyes with cystoid macular edema or high myopia. Traction to the fovea may cause partial- and full-thickness macular defects. Partial-thickness defects are foveal pseudocysts, macular pseudoholes, and tractional, degenerative, and outer lamellar holes. The morphology of the foveal defects can be partly explained by the shape of Müller cells and the location of tissue layer interfaces of low mechanical stability. Because Müller cells and astrocytes provide the structural scaffold of the fovea, they are active players in mediating tractional alterations of the fovea, in protecting the fovea from such alterations, and in the regeneration of the foveal structure. Tractional and degenerative lamellar holes are characterized by a disruption of the Müller cell cone in the foveola. After detachment or disruption of the cone, Müller cells of the foveal walls support the structural stability of the foveal center. After tractional elevation of the inner layers of the foveal walls, possibly resulting in foveoschisis, Müller cells transmit tractional forces from the inner to the outer retina leading to central photoreceptor layer defects and a detachment of the neuroretina from the retinal pigment epithelium. This mechanism plays a role in the widening of outer lameller and full-thickness macular holes, and contributes to visual impairment in eyes with macular disorders caused by conractile epiretinal membranes. Müller cells of the foveal walls may seal holes in the outer fovea and mediate the regeneration of the fovea after closure of full-thickness holes. The latter is mediated by the formation of temporary glial scars whereas persistent glial scars impede regular foveal regeneration. Further research is required to improve our understanding of the roles of glial cells in the pathogenesis and healing of tractional macular disorders.

A mechanical model of posterior vitreous detachment and generation of vitreoretinal tractions.

We propose a mechanical model of generation of vitreoretinal tractions in the presence of posterior vitreous detachment (PVD). PVD is a common occurrence with aging, and it consists in the separation of the vitreous body from the retina at the back pole of the eye, due to progressive shrinking of the vitreous gel. During this separation process, vitreoretinal tractions are generated at regions of high adhesion between the vitreous and the retina. Such tractions are mainly responsible for the creation of retinal tears, which can lead to retinal detachment. We describe the PVD evolution developing a continuum model of a shrinking soft body, representing the vitreous humor gel phase. In the model, the vitreous is surrounded by a membrane, stiffer than the bulk, the vitreous cortex, and it is contained within a rigid spherical domain, the vitreous chamber. The membrane is attached to the spherical wall and the adhesion strength is spatially non-uniform, increasing from the back to the front of the chamber, according to clinical observations. During the shrinking process, the vitreous undergoes elastic distortions, owing to the spatially variable adhesion on the wall, and this produces boundary tractions. We also consider the clinically relevant case of anomalous PVD, in which regions of focal adhesion between the vitreous and the retina exist, leading to the generation of strong, localized tractions. The model reproduces a PVD evolution in good qualitative agreement with clinical observations and makes it possible to correlate the shape of the detached vitreous with the intensity of vitreoretinal tractions.

Pharmacotherapy of Vitreomacular Traction.

Vitreomacular traction occurs due to incomplete or anomalous posterior vitreous detachment. Over time, the vitreous pulls anteriorly and causes retinal distortion and eventually reduced vision. Traditionally, vitreomacular traction was treated with vitrectomy surgery. In the past few years, there is a paradigm shift towards pharmacologic vitreolysis, which involves the intravitreal injection of enzymatic and non-enzymatic agents that facilitate posterior vitreous detachment. Many agents have been investigated and trialled including plasmin, microplasmin (Ocriplasmin), hyaluronidase, nattokinase, chondroitinase and dispase. This review will focus on the progress and current status in this research.

The Pathophysiology of Vitreomacular Interface Disease

Anomalous posterior vitreous detachment is an important step in the pathogenesis of vitreoretinal interface diseases. In order to understand the pathophysiology of vitreoretinal interface diseases, the structure and biochemistry of the vitreous body, and its relation with the retina should be investigated. Having a clear understanding of the pathophysiology of these diseases may help to develop new pharmacologic or surgical treatment modalities.

Efficacy of non-fovea-sparing ILM peeling for symptomatic myopic foveoschisis with and without macular hole

AimTo study anatomical and visual outcomes of pars plana vitrectomy (PPV) with non-fovea-sparing (entire) internal limiting membrane (ILM) peeling in eyes with myopic foveoschisis (MF).MethodsProspective interventional case series of eyes...

Vitreomacular Traction Following Anti-VEGF Therapy - Two Cases

Vitreomacular traction syndrome (VMTS) is defined as an incomplete or anomalous posterior vitreous detachment resulting in tractional forces at the macular region. In the context of anti-VEGF therapy, the formation of vitreoretinal traction has mainly been reported as a potential complication of VEGF inhibition in ischemic proliferative retinal disease, such as proliferative diabetic retinopathy. In this report, we present two patients who developed VMTS during anti-VEGF therapy for exudative age-related macular degeneration and diabetic macular edema. VMTS following anti-VEGF therapy of exudative macular diseases is rare. The exact pathomechanism remains unclear. However, there is a hypothesis that in eyes with adherent vitreous cortex, the induction of fibrosis as a result of the VEGF inhibition may lead to vitreomacular traction.

Prevention of retinal detachment

SummaryRhegmatogenous retinal detachment (RRD) is usually caused by peripheral retinal breaks related to anomalous posterior vitreous detachment (PVD). A smaller percentage is caused by atrophic retinal holes or traumatic dialysis of the ora serrata in the absence of a PVD. Although RRD affects only a small percentage of the general population, it can cause significant vision loss. A 5–10% of retinal reattachment attempts may fail whereas only half of the eyes with reattached retinas will maintain ≥ 20/50 vision. Furthermore, RRD repair harbours complications such as endophthalmitis, cataracts and diplopia. Prevention of RRD is therefore important. In this course we will explore the risk factors predisposing to RRD and will discuss preventive measures.

From the analysis of pharmacologic vitreolysis to the comprehension of ocriplasmin safety

ABSTRACTIntroduction: Pharmacologic vitreolysis is a strategy used to treat anomalous posterior vitreous detachment, by weakening vitreoretinal adhesion with an intravitreal drug. Pharmacologic vitreolysis facilitates surgery, and abnormalities of the vitreoretinal interface including vitreomacular traction (VMT) and early stage macular hole (MH) could be resolved. Ocriplasmin is a recombinant protease, active against fibronectin and laminin, which are important components of the vitreoretinal interface. Ocriplasmin has been approved for symptomatic treatment of VMT and MH with visible traction, and it functions by dissolving the proteins that link the vitreous to the macula, thereby creating a complete posterior vitreous detachment (PVD).Areas covered: This paper reviews the current knowledge and status of investigations regarding the use of ocriplasmin for pharmacologic vitreolysis and its safety.Expert opinion: Ocriplasmin is a non-specific enzyme; therefore, it dissolves vitreal proteins as well as possibly proteins associated with visual function in the retina, choroid, and lens. Ocular adverse events (OAEs) of ocriplasmin include transient visual loss, intraocular inflammation, vitreous floaters, lens opacification, zonular instability of the lens, and intraocular hemorrhage. The prevalence of the OAEs is very low; however, on rare occasions, they can result in widespread retinal dysfunction. Research into the acute and long-term safety of ocriplasmin is required.

Vitreoretinal Traction and Lamellar Macular Holes Associated with Cicatricial Toxoplasmic Retinochoroiditis: Case Series Report

Inflammation due to retinal neuroepithelial necrotic granulomas of toxoplasmosis can extend to neighbor areas and may develop focal adhesions of the posterior hyaloid, to the surface vessels, and the margins or adjoining areas of retinochoroiditis plaques. These adhesions may develop vitreoretinal traction and retinal tears. Vitreoretinal traction may be macular (VMT) or extramacular depending on the location of the toxoplasmic plaques. Vitreomacular traction may follow anomalous posterior vitreous detachment. We report 7 cases of vitreoretinal traction (macular or peripheral) and the development of 4 lamellar macular holes in cicatricial toxoplasmic retinochoroiditis. This is a retrospective and observational study by revision of clinical records in a retinologist office, using diagnostic techniques, especially optical coherence tomography (OCT), current management, and an extended follow-up. The OCT observations on toxoplasmic extramacular plaques are more difficult. Seven cases in 5 patients, 2 of them bilateral, 3 male (66.6%) and 2 female, median age 46 years, were included. Anteroposterior VMT was found in 6 cases and another case was superotemporal midperipheral; 4 developed lamellar macular holes and 3 chronic macular epiretinal membranes. Best-corrected visual acuity was equal to or better than 20/30 in 3 cases, between 20/50 and 20/80 in 2 cases, and 20/160 to 20/200 in 2 cases. One small lamellar macular hole closed spontaneously during follow-up. Inflammatory retinal granulomas of toxoplasmosis in cicatricial stages may present macular or peripheral focal vitreoretinal adhesions that can eventually lead to VMT and subsequent lamellar macular holes or peripheral retinal tears.

Pharmacologic vitreolysis with ocriplasmin: rationale for use and therapeutic potential in vitreo-retinal disorders.

With increased knowledge about the origins and pathophysiology of vitreo-retinal disorders—and, in particular, the central role of anomalous posterior vitreous detachment in vitreo-maculopathies—a paradigm shift from surgery to pharmacotherapy is taking place with the development of pharmacologic vitreolysis. The first approved agent for pharmacologic vitreolysis therapy is ocriplasmin, a truncated form of the nonspecific serine protease plasmin. Twelve studies comprise the current ocriplasmin clinical trial program, demonstrating the efficacy and safety of a single intravitreal injection of ocriplasmin for the treatment of patients with symptomatic vitreo-macular adhesion or vitreo-macular traction, including patients with macular holes. Although post-approval implementation of ocriplamsin in clinical practice has shown success rates of up to 78%, there have been recent case reports of acute, transient visual dysfunction. There are thus new initiatives to further refine clinical indications for case selection and to identify possible untoward effects. Although more studies are warranted, it appears that ocriplasmin offers a good alternative to surgery. The future lies in pharmacologic vitreolysis, and the future of pharmacologic vitreolysis lies in prevention. Thus, long-term studies are needed to define a role for pharmacologic vitreolysis, in particular with ocriplasmin, in the prevention of progressive diabetic retinopathy and age-related macular degeneration.

The vitreoretinal interface and its role in the pathogenesis of vitreomaculopathies

The vitreoretinal interface consists of the inner limiting membrane of the retina, the posterior vitreous cortex, and an intervening extracellular matrix. Hyalocytes are mononuclear phagocytes embedded in the posterior vitreous cortex, in a single layer of sparse density. At the macula, anomalous posterior vitreous detachment (PVD) results in either full-thickness vitreous cortex adhesion with vitreomacular traction syndrome, or partial-thickness adhesion due to vitreoschisis, a split in the posterior vitreous cortex. Anomalous PVD with vitreoschisis splitting behind the level of the monolayer of hyalocytes leaves a relatively thin hypocellular membrane attached to the macula. Vitreoschisis anterior to the level of the hyalocytes leaves a thicker cellular membrane. Persistent vitreopapillary adhesion promotes outward (from the fovea) tangential traction and is therefore associated with macular holes. Inward (centripetal) tangential traction results in macular pucker, almost always in the absence of persistent vitreopapillary adhesion. The English full-text version of this article is available at SpringerLink (under supplemental).

Vitreomacular Interface: From Anterior to Tangential Traction.

Anomalous posterior vitreous detachment (PVD) plays a major role in the formation of anterior-posterior and tangential epiretinal traction. Advances in the tomographic analysis of vitreous traction vectors have highlighted the selected cases that can benefit from “parasurgical” approaches, providing a different perspective for therapeutic strategies. The symptomatic anterior-posterior traction recently gained crescent interest for the application of enzymatic vitreolysis (ocriplasmin, IVO), mainly in small traction associated with full thickness macular hole. On the other hand, the outer layer of posterior vitreous cortex leads to tangential traction responsible for the formation of macular pucker. As reported by M. R. Romano et al., the presence of vitreoschisis associated with a strong vitreopapillary adhesion of posterior cortex enhances the force of the tangential vector, inducing potential damage to the inner nuclear and outer plexiform layers. They also reported the epiretinal presence of glial fibrillary acidic protein (GFAP), indicating the ability of these cells to proliferate and migrate on the retinal surface. The transdifferentiated epiretinal cells are characterized by a downregulation of GFAP and cytokeratins, while proteins involved in motility and proliferation, such as α-smooth muscle actin, are upregulated. Therefore, the GFAP content in epiretinal tissues has been shown to correlate directly with tractional forces and inversely with the clinical contractility. D. Compera et al. reported interesting histology findings on the presence of GFAP positive cells in lamellar-hole (LMH) associated epiretinal proliferation. The authors hypothesize that the vitreous derived cells, rather than cells of glial origin, may play a relevant role in the pathogenesis of tangential traction. In LMH, differently from macular pucker, the traction is not increased by the contraction of α-smooth muscle actin (α-SMA), as α-SMA-positive myofibroblasts were an infrequent finding in epiretinal proliferation associated with LMH, in their report. D. Agarwal et al. highlighted the presence of a tangential traction due to the thickened premacular vitreous cortex in diabetic patients. The authors also described a significant relationship between PVD and lack of macular edema, suggesting the importance of the vitreous cortex, embedded with fibroblasts and astrocytes, in the development and progression of diabetic retinopathy. The different adhesion at the interfaces seems to be sustained by factors such as VEGF, CCL2, IL-6, IL-8, and IL-18, also encouraging neovascularization and therefore worsening visual outcome. Surgical treatment is still the main approach in the management of the tangential tractional membranes. F. Semeraro et al. showed that the pathological vitreoretinal adhesion on the inner limiting membrane (ILM) offers different surfaces on which transdifferentiated glial cells migrate and thereby configures different aspects of traction maculopathies. The removal of ILM has become a routine practice in the surgery of the epiretinal membranes (ERM). However, many recent studies have shown that ILM peeling may cause immediate iatrogenic damage and progressive modification on the underlying inner retinal layers. R. Gelman et al. reported retinal damage induced by ILM peeling including dye-induced toxicity, Muller cell dysfunction, dissociated optic nerve fiber layer, paracentral hole formation, and phototoxic damage. Interestingly, W. J. Mayer et al. reported, in prospective study on 42 eyes, the evidence of mechanical trauma of ERM and ILM peeling due to the use of intraocular forceps that may affect the outer retinal structure. In fact, they observed a significant correlation between the integrity of the ellipsoid zone and retinal sensitivity, overall and in the peeled areas. M. Asencio-Duran et al. reported that the earliest change in the macula is postoperative swelling of the arcuate retinal nerve fiber layers that appears as hypoautofluorescent arcuate striae on infrared and autofluorescence imaging. Such findings induced by the swelling may disappear in 3 months; however they may potentially cause permanent functional damage in patients already affected by glaucoma. Finally, vitreomacular adhesion (VMA) can also affect the progression of the age-related macular degeneration (AMD), as reported by E. C. Kang and H. J. Koh. In neovascular AMD, VMA may induce inflammation, decrease in oxygenation, and sequestering of VEGF and other cytokines. Moreover, VMA may also interfere with the therapeutical effects of anti-VEGF treatment. Considering movement towards future, a more updated classification of the tangential traction is needed, whereas the anterior-posterior traction has been better classified thanks to the recent interest in the enzymatic vitreolysis. Mario R. Romano Xavier Valldeperas John Byron Christoforidis

Clinicopathological correlations at the vitreoretinal interface

Clinicopathological studies of the vitreoretinal interface (VRI) improve our understanding of the pathogenesis of vitreal maculopathy, facilitate differential diagnoses and help to develop new treatment strategies. The aim of the study was to provide a comprehensive overview on clinicopathological correlations of the VRI. A semi-structured literature search was performed in the Medline and Embase databases for relevant original studies on clinicopathological correlations of vitreal maculopathy, in addition to the latest books and review articles. Age-related vitreous changes with persistent vitreomacular adhesions on the retinal surface promote cellular migration and proliferation onto the vitreal side of the internal limiting membrane (ILM), thereby cementing the vitreomacular adhesions and strengthening the traction forces on retinal layers. Cellular or fibrocellular proliferation at the vitreomacular interface can be seen in all vitreal maculopathies. Furthermore, vitreoschisis in the context of anomalous posterior vitreous detachment causes the presence of vitreous cortex collagen fibrils on the vitreal side of the ILM which is associated with epiretinal membrane formation. Glial cells, hyalocytes and myofibroblasts represent the major cell types in the epiretinal cell proliferation. Glial cells and hyalocytes are capable of transdifferentiation into myofibroblasts which possess strong contractive properties and are well known for the production of extracellular matrix components. Removing vitreomacular adhesions and vitreous cortex collagen fibrils from the retinal surface is most important for successful treatment. In cases with epiretinal cell proliferation, however, removal of the ILM during macular surgery is mandatory to avoid reproliferation and recurrence. Improving the detection of epiretinal cell proliferation and cell distribution in patient eyes by optical coherence tomography or by introduction of new technologies should be addressed in the future.

Retinal Changes Induced by Epiretinal Tangential Forces.

Two kinds of forces are active in vitreoretinal traction diseases: tangential and anterior-posterior forces. However, tangential forces are less characterized and classified in literature compared to the anterior-posterior ones. Tangential epiretinal forces are mainly due to anomalous posterior vitreous detachment (PVD), vitreoschisis, vitreopapillary adhesion (VPA), and epiretinal membranes (ERMs). Anomalous PVD plays a key role in the formation of the tangential vectorial forces on the retinal surface as consequence of gel liquefaction (synchysis) without sufficient and fast vitreous dehiscence at the vitreoretinal interface. The anomalous and persistent adherence of the posterior hyaloid to the retina can lead to vitreomacular/vitreopapillary adhesion or to a formation of avascular fibrocellular tissue (ERM) resulting from the proliferation and transdifferentiation of hyalocytes resident in the cortical vitreous remnants after vitreoschisis. The right interpretation of the forces involved in the epiretinal tangential tractions helps in a better definition of diagnosis, progression, prognosis, and surgical outcomes of vitreomacular interfaces.

Idiopathic epiretinal membrane.

Idiopathic epiretinal membrane (iERM) is a fibrocellular membrane that proliferates on the inner surface of the retina at the macular area. Membrane contraction is an important sight-threatening event and is due to fibrotic remodeling. Analysis of the current literature regarding the epidemiology, clinical features, and pathogenesis of iERM and fibrotic tissue contraction. Epidemiologic studies report a relationship between iERM prevalence, increasing age, and posterior vitreous detachment. Clinically, iERM progresses through different stages characterized by an increased thickness and wrinkling of the membrane. Pathophysiologically, iERM formation is a fibrotic process in which myofibroblast formation and the deposition of newly formed collagens play key roles. Anomalous posterior vitreous detachment may be a key event initiating the formation of iERM. The age-related accumulation of advanced glycation end products may contribute to anomalous posterior vitreous detachment formation and may also influence the mechanical properties of the iERM. Remodeling of the extracellular matrix at the vitreoretinal interface by aging and fibrotic changes, plays a significant role in the pathogenesis of iERM. A better understanding of molecular mechanisms underlying this process may eventually lead to the development of effective and nonsurgical approaches to treat and prevent vitreoretinal fibrotic diseases.

Hyalocytes in idiopathic epiretinal membranes: a correlative light and electron microscopic study.

To describe characteristics of epiretinal cells at the vitreoretinal interface by correlative light and electron microscopy (CLEM). Epiretinal membrane (ERM) specimens and internal limiting membrane (ILM) specimens were harvested by sequential peeling during vitrectomy from 27 eyes with idiopathic epiretinal gliosis, and processed for CLEM. Intraoperatively, the presence of posterior vitreous detachment (PVD) was documented. We used anti-vimentin, anti-α-smooth muscle actin (α-SMA), and anti-CD45 as primary antibodies. A fluorescein-tagged immunonanogold cluster was used as secondary antibody and visualized under the fluorescence and transmission electron microscope. We demonstrated CD45-positive cells specifically labelled at their plasma membranes with ultrastructural features known for hyalocytes, such as oval nucleus with marginal chromatin, vacuoles, dense granules, and thin cytoplasmic protrusions. CD45-positive cells were mostly located on a thick layer of native vitreous collagen. They were covered by newly formed collagen strands with multilayered proliferation of myofibroblasts. We also demonstrated immunoreactivity for vimentin and alpha-SMA. Cell fragments with positive labelling for α-SMA and vimentin were not only found on the vitreal side of the ILM, but also on the retinal side. By CLEM, the majority of CD45-positive cells in epiretinal cell proliferation were characterized as hyalocytes. In the context of anomalous PVD and vitreoschisis, ultrastructural features and topographic localization of hyalocytes suggest that these cells play a significant role in ERM formation. CLEM enables a more accurate characterization of epiretinal cell proliferation, and therefore, contributes to a better understanding of the pathogenesis of diseases at the vitreoretinal interface.

Profile of ocriplasmin and its potential in the treatment of vitreomacular adhesion.

The recent approval by the US Food and Drug Administration of ocriplasmin for the treatment of symptomatic vitreomacular adhesion (VMA), often associated with vitreomacular traction (VMT) and macular hole (MH), has brought new attention to the field of pharmacologic vitreolysis. The need for an enzyme to split the vitreomacular interface, which is formed by a strong adhesive interaction between the posterior vitreous cortex and the internal limiting membrane, historically stems from pediatric eye surgery. This review summarizes the different anatomic classifications of posterior vitreous detachment or anomalous posterior vitreous detachment and puts these in the context of clinical pathologies commonly observed in clinical practice of the vitreoretinal specialist, such as MH, VMT, age-related macular degeneration, and diabetic macular edema. We revisit the outcome of the Phase II studies that indicated ocriplasmin was a safe and effective treatment for selected cases of symptomatic VMA and MH. Release of VMA at day 28 was achieved by 26.5% of patients in the ocriplasmin group versus 10.1% in the placebo group (P<0.001). Interestingly, for MHs, the numbers were more remarkable. Predictive factors for successful ocriplasmin treatment were identified for VMT (VMA diameter smaller than 1,500 μm) and MH (smaller than 250 μm). In comparison with the highly predictable outcome after vitrectomy, the general success rate of ocriplasmin not under clinical trial conditions has not fully met expectations and needs to be proven in real-world clinical settings. The ocriplasmin data will be compared in the future with observational data on spontaneous VMA release, will help retina specialists make more accurate predictions, and will improve outcome rates.