Vitreomacular Interface Diseases
Over the past two decades, the role of vitreomacular adhesion in vitreomacular interface pathologies, such as vitreomacular traction syndrome, epiretinal membrane and macular hole, has been increasingly recognized. Abnormalities of the vitreoretinal interface may contribute to important retinal pathologies such as diabetic retinopathy, diabetic macular edema and age-related macular degeneration. The prevalence of many of these serious disorders is rising. Eyes with vitreomacular adhesion-related disorders can experience rapid deterioration of vision and function if not managed in a timely and effective manner. The only treatment option currently available is vitrectomy. Pharmacologic treatment options have advanced over the past decade, and the current strategy of 'watchful waiting' until symptoms worsen may not be acceptable in the future. This article reviews vitreomacular interface disorders, and explores the evidence of experimental agents that can potentially treat these conditions.
The search to define the role of the vitreous in eye disorders has long been neglected because the vitreous consists mostly of water and is optically transparent and, therefore, difficult to visualize. The vitreous has been known for its ability to detach the retina by exerting tractional forces on it, thereby inducing holes or tears; its role in the pathophysiology of other ocular conditions is becoming better understood due to advancements in imaging and diagnostics. Data in the literature suggest that the vitreous contributes to the pathogenesis of vitreomacular traction (VMT), macular holes, macular edema, proliferative retinopathies, retinal vein occlusion and exudative age-related macular degeneration. Patients can have a poor prognosis if left untreated. The disorders must be managed appropriately and in a timely manner, since rapid visual deterioration and potential blindness may occur. For instance, with untreated VMT, vision deteriorates over time, because spontaneous vitreomacular separation occurs infrequently in these patients. Data suggest that the longer the duration of symptoms, the worse the prognosis when surgical treatment is employed. Such conditions do not have any treatment options available today until the disease progressively worsens to the point where a significant decrease in visual acuity warrants eye surgery (vitrectomy).
Surgical vitrectomy has been developed to overcome pathologic conditions related to the vitreous body and retina, and is in widespread use in specialist centers. The extent and difficulty of vitreous surgery depends on the degree of adhesion between the vitreous body and the retina. Although the techniques and instruments for vitreous surgery have been improved in recent years, the surgical removal of the vitreous cortex is still challenging with risk of incomplete vitreoretinal separation, risk of complications, both intraoperative and postoperative (Box 1), as well as a significant treatment burden for the patient and the patient's family and care givers, with associated financial implications. Intraoperative risks include the occurrence of retinal tears (15%) including retinal detachments (1.2–6.6%) as well as damage to internal ocular structures, which can lead to hemorrhage. There is an additional risk associated with general anesthesia in this age group. Postoperative risks include low intraocular pressure, infection, inflammation, choroidal detachment, macular edema and vitreous hemorrhage. Cataract is a very common long-term postoperative complication of vitrectomy, occurring in the vast majority of phakic patients, thereby leading to the need for an additional surgical procedure (cataract extraction) and its consequent risks. In addition to these intraoperative and postoperative risks, vitrectomy entails a significant treatment burden for the patient and their family as outlined in Box 2. Therefore, surgery is used only as an intervention when patients have or are at risk of severe visual disturbance and/or central blindness. However, this means many patients undergo a period of 'watchful waiting' when the patients' symptoms remain untreated until these get severe enough to warrant a major surgical procedure. In some cases, this 'watchful waiting' can lead to irreversible damage to the retina, such that the eventual prognosis is adversely affected. The difference in visual function loss between 'watchful waiting' until symptoms are severe enough for surgery and upon earlier intervention is schematically shown in Figure 1.
(Enlarge Image)
Figure 1.
Progression of symptomatic vitreomacular adhesion until (A) symptoms are severe enough to warrant standard vitrectomy and (B) upon earlier intervention.
It is thus not surprising that over the past decades investigators have been exploring alternative methods to vitrectomy. A minimally invasive, less traumatic and well-tolerated treatment option would represent a significant advance in care. The goal is to relieve tractional effects on the macula, thereby resolving the underlying condition with subsequent functional improvement. Most efforts were directed at pharmacological agents, which modify the molecular structure of the vitreous and its attachment to the retina, which has been called 'pharmacological vitreolysis'.
The aim of this review is to summarize the current knowledge on disorders related to the vitreomacular interface with focus on vitreomacular adhesion and macular hole. The anatomy and physiology of the vitreous is briefly reviewed for a better understanding of the treatment options. A brief overview of vitreoretinal surgery is discussed, as well as agents that have been evaluated for pharmacologic vitreolysis. Finally, an expert view on the treatment of the disorders is given and future trends are highlighted.
Abstract and Introduction
Abstract
Over the past two decades, the role of vitreomacular adhesion in vitreomacular interface pathologies, such as vitreomacular traction syndrome, epiretinal membrane and macular hole, has been increasingly recognized. Abnormalities of the vitreoretinal interface may contribute to important retinal pathologies such as diabetic retinopathy, diabetic macular edema and age-related macular degeneration. The prevalence of many of these serious disorders is rising. Eyes with vitreomacular adhesion-related disorders can experience rapid deterioration of vision and function if not managed in a timely and effective manner. The only treatment option currently available is vitrectomy. Pharmacologic treatment options have advanced over the past decade, and the current strategy of 'watchful waiting' until symptoms worsen may not be acceptable in the future. This article reviews vitreomacular interface disorders, and explores the evidence of experimental agents that can potentially treat these conditions.
Introduction
The search to define the role of the vitreous in eye disorders has long been neglected because the vitreous consists mostly of water and is optically transparent and, therefore, difficult to visualize. The vitreous has been known for its ability to detach the retina by exerting tractional forces on it, thereby inducing holes or tears; its role in the pathophysiology of other ocular conditions is becoming better understood due to advancements in imaging and diagnostics. Data in the literature suggest that the vitreous contributes to the pathogenesis of vitreomacular traction (VMT), macular holes, macular edema, proliferative retinopathies, retinal vein occlusion and exudative age-related macular degeneration. Patients can have a poor prognosis if left untreated. The disorders must be managed appropriately and in a timely manner, since rapid visual deterioration and potential blindness may occur. For instance, with untreated VMT, vision deteriorates over time, because spontaneous vitreomacular separation occurs infrequently in these patients. Data suggest that the longer the duration of symptoms, the worse the prognosis when surgical treatment is employed. Such conditions do not have any treatment options available today until the disease progressively worsens to the point where a significant decrease in visual acuity warrants eye surgery (vitrectomy).
Surgical vitrectomy has been developed to overcome pathologic conditions related to the vitreous body and retina, and is in widespread use in specialist centers. The extent and difficulty of vitreous surgery depends on the degree of adhesion between the vitreous body and the retina. Although the techniques and instruments for vitreous surgery have been improved in recent years, the surgical removal of the vitreous cortex is still challenging with risk of incomplete vitreoretinal separation, risk of complications, both intraoperative and postoperative (Box 1), as well as a significant treatment burden for the patient and the patient's family and care givers, with associated financial implications. Intraoperative risks include the occurrence of retinal tears (15%) including retinal detachments (1.2–6.6%) as well as damage to internal ocular structures, which can lead to hemorrhage. There is an additional risk associated with general anesthesia in this age group. Postoperative risks include low intraocular pressure, infection, inflammation, choroidal detachment, macular edema and vitreous hemorrhage. Cataract is a very common long-term postoperative complication of vitrectomy, occurring in the vast majority of phakic patients, thereby leading to the need for an additional surgical procedure (cataract extraction) and its consequent risks. In addition to these intraoperative and postoperative risks, vitrectomy entails a significant treatment burden for the patient and their family as outlined in Box 2. Therefore, surgery is used only as an intervention when patients have or are at risk of severe visual disturbance and/or central blindness. However, this means many patients undergo a period of 'watchful waiting' when the patients' symptoms remain untreated until these get severe enough to warrant a major surgical procedure. In some cases, this 'watchful waiting' can lead to irreversible damage to the retina, such that the eventual prognosis is adversely affected. The difference in visual function loss between 'watchful waiting' until symptoms are severe enough for surgery and upon earlier intervention is schematically shown in Figure 1.
(Enlarge Image)
Figure 1.
Progression of symptomatic vitreomacular adhesion until (A) symptoms are severe enough to warrant standard vitrectomy and (B) upon earlier intervention.
It is thus not surprising that over the past decades investigators have been exploring alternative methods to vitrectomy. A minimally invasive, less traumatic and well-tolerated treatment option would represent a significant advance in care. The goal is to relieve tractional effects on the macula, thereby resolving the underlying condition with subsequent functional improvement. Most efforts were directed at pharmacological agents, which modify the molecular structure of the vitreous and its attachment to the retina, which has been called 'pharmacological vitreolysis'.
The aim of this review is to summarize the current knowledge on disorders related to the vitreomacular interface with focus on vitreomacular adhesion and macular hole. The anatomy and physiology of the vitreous is briefly reviewed for a better understanding of the treatment options. A brief overview of vitreoretinal surgery is discussed, as well as agents that have been evaluated for pharmacologic vitreolysis. Finally, an expert view on the treatment of the disorders is given and future trends are highlighted.