Pigment Epithelial Detachment (PED) is a structural finding in the eye, characterized by the separation of the Retinal Pigment Epithelium (RPE) layer from the underlying Bruch’s membrane. This separation occurs due to an accumulation of fluid or other material within the sub-RPE space, creating a dome-shaped elevation. PED is not a disease itself but a common manifestation of various retinal conditions, most frequently Age-Related Macular Degeneration (AMD). Treatment strategies are highly specialized and depend entirely on the specific material causing the separation.
Differentiating Types of Pigment Epithelial Detachment
Accurate classification of the material causing the detachment dictates the treatment pathway for PED.
One common type is drusenoid PED, characterized by the accumulation of soft drusen material, a lipoproteinaceous debris associated with dry AMD. These detachments typically have a smooth, dome-shaped contour and often precede the development of advanced disease.
A serous PED involves the accumulation of clear, transudative fluid between the RPE and Bruch’s membrane. This type is frequently associated with non-neovascular AMD or Central Serous Chorioretinopathy (CSC), where fluid leaks from the choroidal blood vessels. Serous PEDs usually present with sharply demarcated borders.
The most vision-threatening type is the vascularized or fibrovascular PED, defined by the presence of Choroidal Neovascularization (CNV)—abnormal, leaking blood vessels—underneath the RPE. This subtype is almost exclusively associated with neovascular (“wet”) AMD and requires aggressive intervention. Finally, a hemorrhagic PED is an acute and severe variant of the fibrovascular type, involving a significant accumulation of blood that separates the RPE from the choroid.
Treatment Strategies for Serous and Drusenoid PED
Treatment for detachments not driven by active Choroidal Neovascularization focuses on monitoring and supportive care. Drusenoid PEDs are managed conservatively as they represent a stage of dry AMD. Patients are advised to take specific high-dose antioxidant and mineral supplements, such as the Age-Related Eye Disease Study (AREDS) formulation, to slow AMD progression. The primary goal is monitoring for conversion to neovascular AMD. Active treatment for the drusenoid detachment itself is avoided, as many detachments may spontaneously resolve.
Serous PEDs, often associated with Central Serous Chorioretinopathy (CSC), are treated by targeting underlying choroidal hyperpermeability. Initial management involves observation, as many acute CSC cases resolve spontaneously within a few months. If the serous detachment persists and causes chronic visual symptoms, intervention is warranted.
A preferred treatment for chronic serous PED is Photodynamic Therapy (PDT) using the photosensitizing drug verteporfin. This reduced-fluence approach selectively targets the choroidal blood vessels without damaging the overlying RPE. Half-dose PDT has been shown to be superior to other laser treatments in achieving a significant reduction in PED height.
Subthreshold micropulse laser is a non-thermal treatment that can also be used to improve structural and functional outcomes in chronic CSC. The laser uses short bursts of energy to stimulate the RPE, promoting fluid absorption without causing visible burns or scarring.
Anti-VEGF Therapy for Neovascular PED
Fibrovascular PEDs require aggressive therapeutic intervention because they are driven by Choroidal Neovascularization (CNV). CNV involves abnormal vessels that leak fluid and blood into the sub-RPE space, fueled by an overabundance of Vascular Endothelial Growth Factor (VEGF).
The standard of care for fibrovascular PEDs associated with neovascular AMD is the regular, long-term administration of anti-VEGF agents. These medications, including ranibizumab, aflibercept, and bevacizumab, are administered as intravitreal injections to neutralize excessive VEGF. Blocking VEGF suppresses CNV growth and leakage, aiming to flatten the PED and stabilize vision.
Therapy begins with a loading phase of three monthly injections to rapidly suppress the neovascular process. This is followed by a maintenance phase, often using a treat-and-extend protocol where injection intervals are gradually lengthened if the PED remains stable. Fibrovascular PEDs are often resistant and may not completely flatten even with consistent anti-VEGF treatment.
A newer anti-VEGF agent, faricimab, targets both VEGF-A and Angiopoietin-2 (Ang-2). Clinical data indicates that faricimab is associated with a greater reduction in maximum PED thickness compared to aflibercept during the initial loading phase. Faricimab has also shown the ability to reduce PED volume in eyes resistant to high-dose aflibercept, suggesting a potential role for this dual-action mechanism in challenging cases.
Management of Complex and Hemorrhagic PED
Complex and hemorrhagic PEDs often require specialized or combination treatments beyond standard anti-VEGF monotherapy. A hemorrhagic PED is a medical emergency that can lead to rapid vision loss due to the toxic effects of blood components on the photoreceptors.
For large, acute hemorrhagic PEDs, the primary goal is to displace the blood away from the central macula. This is achieved through pneumatic displacement, which involves injecting a gas bubble (e.g., sulfur hexafluoride, \(SF_6\)) into the vitreous cavity. The patient is positioned face-down, allowing the gas bubble to physically push the blood away from the fovea.
This technique is frequently combined with an injection of a thrombolytic agent, such as tissue plasminogen activator (tPA), to liquefy the blood clot. For massive subretinal hemorrhage, a more invasive surgical approach called pars plana vitrectomy may be necessary. This procedure allows for the direct injection of tPA into the subretinal space, followed by fluid-gas exchange to displace the hemorrhage, often combined with an anti-VEGF injection.
For refractory PEDs that fail to flatten despite long-term anti-VEGF treatment, management strategies include switching agents or increasing the dose. A persistent PED is a risk factor for a retinal pigment epithelial (RPE) tear, where the RPE layer rips, causing an abrupt drop in vision. Continuation of anti-VEGF therapy is often recommended to stabilize the underlying neovascular process and preserve remaining vision.