Reticular Pseudodrusen: A Key Risk Factor in AMD
Understanding Reticular Pseudodrusen
Reticular pseudodrusen (RPD), also called subretinal drusenoid deposits (SDD), are small yellowish-white lesions. They form in a net-like pattern beneath the retina. They appear as dot-like structures arranged in clusters, often connected in a web-like or reticular pattern.
RPD are most commonly found in the upper outer area of the macula. The macula is the central part of the retina responsible for sharp, detailed vision.
In standard AMD, drusen deposits accumulate below the retinal pigment epithelium (RPE). The RPE is a critical support layer for the retina. Reticular pseudodrusen are different because they sit above the RPE. They form in the space between the RPE and the photoreceptor cells that detect light.
This location is significant. RPD directly disrupt the photoreceptors, leading to earlier and more noticeable problems with visual function.
Using optical coherence tomography (OCT), a high-resolution scan of the retinal layers, retina specialists classify RPD into three types. This system was developed by Zweifel and colleagues.
- Type 1: Granular material sits between the RPE and the ellipsoid zone without disrupting overlying structures.
- Type 2: The material accumulates into a mound shape over the RPE, causing visible distortion of the ellipsoid zone.
- Type 3: The material forms a cone-like shape that punctures through the ellipsoid zone into the outer retina.
Reticular pseudodrusen cause widespread disruption and loss of both the RPE and the ellipsoid zone. This damage impairs the retina's ability to process light signals. Patients with RPD often notice difficulty seeing in dim lighting before they experience problems in bright conditions.
Who Is Affected and Risk Factors
Age is the strongest risk factor for developing reticular pseudodrusen. The mean age of individuals with RPD is 79 years, compared to 75 years for those without RPD (PMC6875626). RPD prevalence can reach up to 30% in individuals older than 83 years (Ophthalmology Retina, 2021).
Women are more likely to develop RPD than men. Female sex carries an odds ratio of 2.10 for RPD (PMC6875626). Among patients with RPD, 65% are female compared to 53% in those without RPD (PMC6875626).
Specific genetic variants increase the likelihood of developing reticular pseudodrusen. The ARMS2 gene, a well-known AMD risk gene, is strongly associated with RPD. The frequency of the risk allele was 78.6% in patients with RPD compared to 59.9% in those without (PMC6875626). Higher overall genetic risk scores for AMD are also linked to the presence of RPD.
RPD are far more common in eyes with intermediate AMD than in early AMD. In the AREDS2 study, RPD were found in 26% of eyes with intermediate AMD compared to only 6% of eyes with early AMD (PMC6875626). The overall prevalence of RPD in the AREDS2 study population was 29% using autofluorescence imaging (PMC6875626).
Reticular pseudodrusen are particularly common in certain advanced forms of AMD. RPD are present in 83% of eyes with retinal angiomatous proliferation (RAP), a subtype of wet AMD (Pubmed 23111182). They also appear in 50% of eyes with geographic atrophy (Pubmed 23111182). In comparison, RPD appear in only 9% of eyes with typical neovascular AMD and 2% of eyes with polypoidal choroidal vasculopathy (Pubmed 23111182).
Patients with RPD-associated AMD also face higher rates of all-cause mortality compared to patients without RPD (PMC6875626). This finding suggests that RPD may reflect broader systemic health factors beyond the eye. Cardiovascular risk factors such as hypertension and high cholesterol may play a role and should be managed carefully.
Signs and Symptoms
Many patients with reticular pseudodrusen do not notice symptoms in the earliest stages. As RPD progress, one of the first functional changes is difficulty with dark adaptation. Dark adaptation is the ability of the eyes to adjust when moving from a bright environment to a dim one. Research confirms that impaired dark adaptation is associated with AMD severity and RPD (Ophthalmology, 2015).
As RPD disrupt more of the photoreceptor layer and RPE, patients may notice reduced visual sharpness. This is particularly true for tasks that require fine detail. Colors may appear less vivid. Reading in low light becomes increasingly difficult. These changes can occur gradually and may not be obvious without formal testing.
While RPD themselves progress slowly, they increase the risk of complications that require urgent care. If you experience any of the following symptoms, see a retina specialist or go to the emergency room immediately.
- A sudden increase in floaters (spots or threads drifting across your vision)
- Flashes of light in one or both eyes
- A curtain, shadow, or dark area appearing over part of your vision
- Sudden loss of vision in one eye
These symptoms may indicate macular neovascularization (new abnormal blood vessels). This is a treatable but urgent complication.
Diagnosis and Testing
Optical coherence tomography (OCT) is the primary tool for identifying and classifying reticular pseudodrusen. This noninvasive imaging test takes detailed cross-sectional pictures of the retina. A retina specialist can see the granular deposits sitting above the RPE. OCT can distinguish the three types of RPD and track changes over time.
Fundus autofluorescence (FAF) is another key imaging method used to detect RPD. This test captures the natural fluorescence of the RPE layer. It can reveal the reticular pattern of RPD across the macula. The AREDS2 study used FAF imaging to determine RPD prevalence, finding deposits in 29% of participants (PMC6875626). FAF is particularly useful for identifying RPD that may be difficult to see on standard photographs.
During a comprehensive dilated eye exam, a retina specialist may observe the whitish-yellow dot-like structures characteristic of RPD. However, RPD can be subtle on clinical examination alone. Advanced imaging with OCT and autofluorescence is typically needed to confirm their presence and extent.
Patients diagnosed with RPD or any form of AMD should monitor their vision at home using an Amsler grid. This simple chart with a grid of straight lines helps detect new distortion or blank spots in central vision. Any new changes on the Amsler grid should prompt a timely visit to a retina specialist. Changes could signal progression to advanced AMD.
Treatment Options
There is no specific treatment that removes or reverses reticular pseudodrusen at this time. Management focuses on close monitoring for progression and reducing risk factors. Treating complications promptly if they arise is also essential. Patients with RPD and intermediate or advanced AMD should follow the AREDS2 recommendations established by the National Eye Institute (NEI).
The AREDS2 formula, a specific combination of vitamins and minerals, has been shown to reduce the risk of progression to advanced AMD. A retina specialist may recommend AREDS2 supplements for patients with intermediate AMD and RPD. Important lifestyle modifications include the following.
- Smoking cessation, as smoking significantly increases the risk of AMD progression
- Blood pressure control and management of cholesterol levels
- A diet rich in leafy green vegetables, fish, and other sources of omega-3 fatty acids
Wet AMD and dry AMD are different conditions requiring different treatments. If RPD progress and macular neovascularization (wet AMD) develops, the standard treatment is intravitreal anti-VEGF injections (injections of medication into the eye). These medications block vascular endothelial growth factor (VEGF), a protein that drives abnormal blood vessel growth and leakage.
Options include Eylea (aflibercept), Lucentis (ranibizumab), Vabysmo (faricimab), and Avastin (bevacizumab), which is FDA-approved for cancer but used off-label for eye conditions. Anti-VEGF therapy treats wet AMD only and is not used for dry AMD or geographic atrophy.
The choice of medication and injection schedule depends on individual response. Some patients may require injections every four to eight weeks. Newer agents like Eylea HD (high-dose aflibercept) and Vabysmo may allow longer intervals after a loading phase.
Geographic atrophy (GA) is a form of advanced dry AMD, which is a separate condition from wet AMD. Because RPD carry a substantial risk for GA, patients should be aware of the first FDA-approved treatments for this condition.
Syfovre (pegcetacoplan), a complement inhibitor that targets C3, and Izervay (avacincaptad pegol), a complement inhibitor that targets C5, are given as intravitreal injections. These treatments slow the growth of GA lesions but do not restore lost vision. They are specifically for geographic atrophy and are not used for wet AMD.
For patients who develop significant vision loss from geographic atrophy or other advanced AMD complications, low vision rehabilitation can help maintain independence. Magnifying devices, specialized lighting, large-print materials, and electronic reading aids can improve the ability to perform daily tasks.
What to Expect
Patients with RPD typically need regular visits to a retina specialist. Visits are often every three to six months depending on the stage of AMD and the rate of change. Each visit may include OCT imaging, autofluorescence imaging, and visual acuity testing. The retina specialist will look for signs of progression, including growth of RPD, thinning of the RPE, or early signs of geographic atrophy or neovascularization.
RPD tend to progress through the three OCT types over time. Flat deposits (Type 1) may become mound-shaped (Type 2) and then cone-shaped deposits that penetrate the photoreceptor layer (Type 3). As deposits advance, they cause increasing photoreceptor damage and vision loss. RPD are a substantial risk factor for late AMD, particularly for geographic atrophy (PMC6875626).
Not all patients progress to advanced disease. However, the risk is higher than with typical drusen alone.
If anti-VEGF injections become necessary, the procedure is performed in a retina specialist's office. Numbing drops are applied to the eye before the injection. Most patients feel pressure and mild discomfort during and after the procedure. Soreness and a gritty feeling may last for a day or two. Each injection appointment typically takes about 15 to 30 minutes including preparation time.
Living with Reticular Pseudodrusen
Maintaining the vision you have is a central goal of managing RPD. Wearing sunglasses with UV protection when outdoors, eating a nutrient-rich diet, exercising regularly, and avoiding smoking all support retinal health. Following the supplement and monitoring schedule recommended by a retina specialist is important for early detection of any changes.
Because RPD commonly affect the ability to see in dim lighting, practical adjustments at home can improve safety and comfort. Increasing indoor lighting and using nightlights in hallways and bathrooms helps. Allowing extra time for eyes to adjust when entering dark spaces is also useful. Avoiding driving at night when possible can reduce the impact of impaired dark adaptation on daily life.
Learning that you have a condition that increases the risk of vision loss can cause anxiety and stress. It is normal to feel concerned. Speaking with a retina specialist about your specific risk level and monitoring plan can provide reassurance. Support groups for people with macular degeneration, available through organizations like the BrightFocus Foundation, can connect you with others who share similar experiences.
When to See a Retina Specialist
Anyone diagnosed with reticular pseudodrusen should maintain regular appointments with a retina specialist. The frequency of visits depends on your AMD stage and individual risk factors. Do not skip scheduled imaging appointments. Early detection of progression can make a significant difference in treatment outcomes.
Between scheduled visits, contact a retina specialist right away if you notice new distortion on the Amsler grid, a sudden change in vision clarity, new floaters, flashes of light, or any shadow or curtain effect in your visual field. These changes may indicate the development of wet AMD or other complications that benefit from prompt treatment.
Questions and Answers
There is no proven way to prevent reticular pseudodrusen from forming. The strongest risk factors, including age and genetics, cannot be modified. However, managing controllable risk factors such as smoking, high blood pressure, and high cholesterol may help reduce overall AMD progression risk. Regular eye examinations allow early detection, which is important for timely monitoring and intervention if complications develop.
No. While both are deposits associated with AMD, they differ in important ways. Regular drusen sit below the RPE, while reticular pseudodrusen sit above it, directly under the photoreceptors. RPD have a distinct net-like appearance and are more strongly associated with geographic atrophy and certain subtypes of wet AMD than typical drusen. The two types of deposits can occur together in the same eye, and having both may indicate higher risk.
Having reticular pseudodrusen does not mean you will lose your vision. RPD do increase the risk of progressing to advanced AMD, including geographic atrophy and neovascular AMD. However, many patients maintain useful vision for years with proper monitoring and management. Early detection of any progression allows a retina specialist to begin treatment when it can be most helpful.
Yes. Researchers are exploring several promising approaches. A pilot study is evaluating subthreshold laser treatment (a very low-energy laser) for RPD associated with dry AMD. Early results are examining safety and short-term effects. The AMD Ryan Initiative Study (ARIS), supported by the NEI, is tracking 200 people with early reticular pseudodrusen alongside 200 people with early typical AMD. This study aims to better understand how RPD progress and how they differ from standard drusen. These studies may lead to new targeted treatments in the future.
A retina specialist can advise whether AREDS2 supplements are appropriate for your situation. Generally, the AREDS2 formula is recommended for patients with intermediate AMD, which commonly overlaps with RPD. The supplement combination includes vitamin C, vitamin E, lutein, zeaxanthin, zinc, and copper. It is important to use the AREDS2 formula specifically. The original AREDS formula contained beta-carotene, which is no longer recommended due to an increased risk of lung cancer in smokers.