Victor Chong MD, ... Sobha Sivaprasad DM, MS, DNB, FRCS, inRetinal Pharmacotherapy, 2010


Posterior vitreous detachment (PVD) results from weakening of the adhesion between the posterior vitreous cortex and the ILM, in conjunction with liquefaction within the vitreous body. Weakening of the posterior vitreous cortex/ILM adhesion at the posterior pole allows liquid vitreous to enter the retrocortical space via the prepapillary hole. Volume displacement from the central vitreous to the preretinal space causes the observed collapse of the vitreous body.

PVD may exert traction at the vitreoretinal adhesion, leading to hemorrhage, retinal tears, and detachment. Focal attachment in the foveal area can cause vitreomacular traction, with associated diffuse macular edema. Proliferative diabetic retinopathy can be greatly aggravated by anomalous PVD. Effects upon vitreous involve posterior vitreoschisis, where splitting of the posterior vitreous cortex and forward displacement of the vitreous body leave the outer layer of the split posterior vitreous cortex still attached to the retina. This can result in epiretinal membrane, and contribute to macular holes and tractional retinal detachment.


Christos Haritoglou, Anselm Kampik, in Retina (Fifth Edition), 2013

Rationale for pharmacologic vitreolysis

Posterior vitreous detachment (PVD) is a progressive physiological process, involving both syneresis (liquefaction) and synchysis (separation). However, spontaneous PVD is very often incomplete and remnants of the vitreous adhere firmly either to areas in the periphery of the retina or to the macular area in some conditions. Tractional forces exerted by vitreous collagen fibers and/or cellular proliferations at the vitreoretinal interface also play an important role in the pathogenesis of tractional maculopathies such as macular holes, vitreomacular traction syndrome or epimacular membranes. In addition, focal abnormal vitreoretinal adhesions may be implicated in certain types of diabetic macular edema and exudative age-related macular degeneration.1,2

Our present therapeutic approach in these tractional maculopathies is to relieve tractional forces surgically by mechanical means inducing a more or less complete PVD using suction exerted by the vitrectomy probe, followed by a removal of remnants of vitreous collagen fibers and cellular proliferations using endgripping forceps. As we have learned that cellular proliferations tend to recur using remnants of collagen at the internal limiting membrane (ILM) as a scaffold for cellular proliferation, most surgeons tend to remove the ILM during the surgical intervention as well, in order to remove all epiretinal tissue. However, it may be hypothesized that direct manipulation in the area of the macula and the removal of the ILM itself may somehow have an impact on function in the macular area or interfere with the morphological integrity of the retinal layers, especially when being removed with the aid of visualizing agents.3 Therefore, although ILM peeling appears safe from a clinical point of view, it may not be the optimum treatment option with regard to the best possible functional results.

Given this background, a pharmacological liquefaction of the vitreous gel and simultaneous enzymatic separation of vitreous fibrils from the inner aspect of the ILM may result in a resolution of focal vitreomacular adhesions, and this represents an alternative approach to treat traction-related retinal and macular diseases. Leaving the ILM in place and cleaving the vitreoretinal interface at the vitreal side of the ILM, may offer a more complete PVD, and be less traumatic as compared with vitrectomy. This pharmacologic induction of a PVD, if achieved early in the course of retinal or macular diseases, may have also a potential as a prophylactic treatment against advanced stages of potentially sight-threatening conditions such as diabetic retinopathy or AMD.4 This concept is referred to as “pharmacologic vitreolysis,” and was initially introduced by Sebag in 1998.5 Additional potential indications include vitreoretinal procedures for retinal detachment in children, in whom firm adherences of the vitreous often complicate surgery, especially in retinopathy of prematurity or ocular trauma with intraocular foreign body in young persons. The hope is to make vitreoretinal surgery procedures more safe and effective using the concept of pharmacologic vitreolysis.