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Drusen
Macular soft drusen in the right eye of a 70-year-old male.
SpecialtyOphthalmology Edit this on Wikidata
Macular hard drusen and hard exudates in the right eye of a 65-year-old diabetic woman

Drusen, from the German word for node or geode (singular, "Druse"), are tiny yellow or white accumulations of extracellular material that build up between Bruch's membrane and the retinal pigment epithelium of the eye. The presence of a few small ("hard") drusen is normal with advancing age, and most people over 40 have some hard drusen.[1] However, the presence of larger and more numerous drusen in the macula is a common early sign of age-related macular degeneration (AMD).

Classification

[edit]

Drusen associated with aging and macular degeneration are distinct from another clinical entity, optic disc drusen, which is present on the optic nerve head.[2] Both age-related drusen and optic disc drusen can be observed by ophthalmoscopy. Optical coherence tomography scans of the orbits or head, calcification at the head of the optic nerve without change in size of globe strongly suggests drusen in a middle-age or elderly patient.

Whether drusen promote AMD or are symptomatic of an underlying process that causes both drusen and AMD is not known, but they are indicators of increased risk of the complications of AMD.[3]

'Hard drusen' may coalesce into 'soft drusen' which is a manifestation of macular degeneration.[4]

Pathophysiology

[edit]

Around 1850, three authors, Carl Wedl, Franciscus Donders, and Heinrich Müller, gave drusen different labels. Drusen, the hallmark of AMD, were first described in 1854 by Wedl.[5] Wedl named them colloid bodies of the choroid and thought that they were incompletely developed cells. Franciscus Donders[6] called them "Colloidkugeln" (colloid spheres). Later, Heinrich Müller named them by the German word for geode, based on their glittering appearance.[7] He was convinced that drusen originated from the nuclei of the pigment cells, which he believed to belong to the choroid.[8] In view of their location between the retinal pigment epithelium (RPE) and its vascular supply, the choriocapillaris, it is possible that drusen deprive the RPE and photoreceptor cells of oxygen and nutrients. In some cases, drusen develop above the so-called pillars of the choriocapillaris that is the area between two micro vessels;[9] although important variations are observed between different subtypes of AMD.

Drusen in optical coherence tomography.

The source of the proteins and lipids in drusen is also not clear, with potential contributions by both the RPE and the choroid. Several trace elements are present in drusen,[10] probably the most concentrated being zinc.[11] The protein composition of drusen includes apolipoproteins and oxidized proteins, likely originating from blood, RPE, and photoreceptors.[12] Drusen composition also includes members of the complement system. Zinc in drusen has been suggested to play a role in drusen formation by precipitating and inhibiting the elements of the complement cascade, especially complement factor H.[11]

The presence of molecules that regulate inflammation in drusen has led some investigators to conclude that these deposits are a product of the immune system.[13]

Diagnosis

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Usually being asymptomatic, drusen are typically found during routine eye exams where the pupils have been dilated.[14]

Treatment

[edit]

Laser treatment of drusen has been studied. While it is possible to eliminate drusen with this treatment strategy, it has been shown that this fails to reduce the risk of developing the choroidal neovascularisation which causes the blindness associated with age-related macular degeneration.[15]

See also

[edit]

Notes

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Drusen

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Drusen are small, yellow or white extracellular deposits composed primarily of , proteins, and cellular debris that accumulate between the and in the layers of the . These deposits, often visible as distinct spots during eye examinations, are a common age-related finding in the eye and serve as an early indicator of potential retinal pathology. While typically benign in small quantities, larger or more numerous drusen are strongly associated with the development of age-related (), a leading cause of vision loss in older adults. Drusen are classified by size, appearance, and location, with key distinctions including hard drusen (smaller than 63 microns, well-defined, and linked to normal aging) and soft drusen (larger than 125 microns, poorly defined and mound-like, indicating higher risk for progression to advanced ). Intermediate drusen (63–125 microns) and cuticular drusen (25–75 microns, often numerous and aggregating) represent additional subtypes. Primarily occurring in the or peripheral , drusen in the central pose a greater threat to central vision. Separately, refer to calcified clumps of fatty proteins that form in the head, distinct from retinal drusen but also detectable on retinal exams. The formation of drusen is attributed to age-related biochemical changes in the , with risk factors for macular drusen including advancing age (common in individuals over 50, with studies showing prevalence exceeding 90% for hard drusen), , , high , high , and family history, particularly among populations. may have a genetic component, often appearing in families, though their exact remains unclear. Clinically, the presence of extensive soft drusen or multiple intermediate drusen elevates the 5-year risk of progressing to advanced up to 13% in bilateral cases, underscoring their prognostic value. Drusen can also occur in other conditions, such as or Sorsby fundus dystrophy, but their hallmark role remains in AMD monitoring.

Overview

Definition and Characteristics

Drusen are small, yellow or white extracellular deposits primarily composed of , proteins, and cellular , situated between the (RPE) and or within the head. These deposits appear as dome-shaped elevations visible during ophthalmoscopic examination, with sizes classified as small (less than 63 μm in diameter), intermediate (63–125 μm), or large (greater than 125 μm). Histologically, drusen consist of accumulations that include apolipoproteins such as apolipoprotein E, complement factors like C5 and the C5b-9 complex, and amyloid-like structures including amyloid-beta peptides. These components contribute to the deposits' characteristic structure, distinguishing them from other retinal changes. While small, hard drusen are a normal aging finding present in over 90% of individuals by age 50, larger soft drusen indicate higher AMD risk and are pathological extracellular accumulations, unlike normal aging processes, which involve intracellular lipofuscin accumulation within RPE cells. Drusen serve as an early hallmark of age-related macular degeneration (AMD).

Epidemiology and Risk Factors

Drusen are commonly observed in the eyes of older adults, with prevalence increasing markedly with age. Any drusen are common, present in over 95% of individuals by age 50, but clinically significant large or soft drusen increase from about 2% in those aged 40-50 to over 25% by age 75, with early features (including soft drusen) at 2.2% in 43-54 years and 27.9% in 75-84 years per the Beaver Dam Eye Study. These deposits serve as precursor lesions for , with higher burdens correlating with greater risk of progression to advanced disease. Demographic factors play a key role in drusen development, with age being the strongest non-modifiable , as onset typically occurs after 50 years and escalates thereafter. Data on differences are conflicting; some studies show a slight predominance in females for overall , while others indicate higher rates of soft drusen in males (e.g., age-adjusted of large drusen ~2.5-4.7% in both genders but varying by age and ). Ethnic variations are notable, with higher among Caucasians; large drusen (>125 μm) are more prevalent in older white individuals (up to 25-30% in those ≥80 years) compared to populations (around 10-14% in ≥80 years), though small drusen (≥64 μm) occur at similar rates across ethnicities (~20% in older adults) but with fewer progressing to large in non-whites. In contrast, and groups exhibit lower overall drusen burden compared to Caucasians, per multi-ethnic cohort data. Genetic and environmental factors further influence drusen formation. Variants in the complement (CFH) gene, such as Y402H, and ARMS2/HTRA1 locus increase susceptibility, with odds ratios ranging from 2- to 7-fold for developing drusen or early depending on and combination. is a major modifiable risk, approximately doubling the odds of drusen presence and progression through mechanisms. exposure has been implicated as an environmental contributor, with prolonged history associated with higher drusen risk in some analyses. Cardiovascular comorbidities, including and , also elevate risk, likely via vascular and inflammatory pathways shared with . Recent 2025 data from the American Academy of Ophthalmology (AAO) highlight emerging insights into ethnic disparities, showing lower drusen burden in non-Caucasian populations but confirming the presence of subretinal drusenoid deposits (a subtype) in and patients for the first time, with potentially higher progression risks in these groups despite reduced initial prevalence. These findings underscore the need for targeted screening in diverse populations to address varying drusen-related trajectories.

Classification

Macular Drusen

Macular drusen are extracellular deposits located between the (RPE) and in the macular region, often appearing as yellowish lesions that can be discrete or . These deposits are typically graded by size (e.g., small <63 μm, intermediate 63-125 μm, large >125 μm) and total area covered within standardized regions, such as the Early Treatment Study (ETDRS) grid, which divides the into concentric circles centered on the fovea for precise quantification. Soft macular drusen, in particular, tend to be larger, more ill-defined, and prone to , contributing to a higher-risk compared to harder variants. Macular drusen are classified into subtypes based on morphology and location, with hard drusen characterized as small (<63 μm), discrete, and punctate, generally posing a lower risk for progression. In contrast, soft drusen are larger (>125 μm), amorphous, and more closely associated with age-related (AMD), serving as a hallmark of intermediate dry AMD. A distinct variant, subretinal drusenoid deposits (SDDs)—also known as pseudodrusen—are located above the RPE in the subretinal space and often present as dot- or ribbon-like lesions; these are more prevalent in advanced AMD stages and indicate a separate pathway to or neovascularization. Clinically, macular drusen represent an early marker of dry , with their presence and characteristics guiding risk stratification. Large drusen (>125 μm) substantially elevate the risk of progression to neovascular , increasing it by approximately 3-4 times compared to smaller drusen, particularly when confluent or accompanied by pigmentary changes. This heightened risk underscores the importance of monitoring macular drusen for timely intervention in management. Recent 2025 research, including presentations at the American Academy of Ophthalmology (AAO) annual meeting, has highlighted SDDs as underrecognized high-risk features in and patients with , where they occur in about 43% of cases and are linked to vascular comorbidities such as and , similar to patterns in White patients. These findings, drawn from a of 23 such patients, emphasize the need for enhanced screening in diverse populations to address disparities in progression.

Optic Disc Drusen

Optic disc drusen are calcified deposits located within the head, anterior to the lamina cribrosa, and can be either superficial or buried. These acellular concretions primarily consist of calcium, along with mitochondria-derived material, , nucleic acids, mucopolysaccharides, and occasionally iron. They share an extracellular deposit nature with macular drusen but differ in their calcified, nerve-head localization. The condition is often bilateral, affecting 70-80% of cases. On fundus examination, superficial optic disc drusen typically appear as small, refractile, yellow-white bodies clustered at the optic disc margin, while buried drusen may lead to an elevated disc appearance with blurred margins due to axonal crowding in a congenitally small scleral canal. The prevalence in the general population ranges from 0.3% to 2.4%, with rates of about 0.4% observed in children, increasing to approximately 2% by adulthood as drusen become more visible. This elevated disc elevation can mimic pseudopapilledema, necessitating differentiation from true papilledema via imaging. Optic disc drusen are associated with defects, including arcuate scotomas, in 20-30% of affected eyes, particularly those with visible surface drusen, due to compression of fibers. Rare complications include , resulting from vascular compromise at the crowded head. As of 2025, updated pathogenesis models emphasize aberrant axoplasmic transport leading to axonal degeneration, mitochondrial , and glial as key drivers of drusen formation and progression, with slowed flow expelling damaged mitochondria extracellularly for progressive .

Pathophysiology

Formation and Composition

Drusen formation begins with the accumulation of extracellular debris in the subretinal pigment epithelium (RPE) space, primarily due to impaired by RPE cells of shed photoreceptor outer segments. This process leads to the buildup of undigested cellular material, including and proteins, which serve as a nidus for further deposition. from retinal metabolism and environmental factors exacerbates this by promoting and triggering local , which in turn activates the , resulting in the deposition of components such as C3 and the membrane attack complex C5b-9 within the forming deposits. The biochemical composition of drusen is dominated by , which constitute approximately 40% of their volume, primarily in the form of esters (about 33%) and (about 33%), alongside smaller amounts of triglycerides, free fatty acids, and unesterified . Proteins make up around 38% of drusen content, including acute-phase reactants like and , as well as complement proteins (e.g., C3, C5, C9, and ) and amyloid-beta, with the drusen characterized through revealing over 100 distinct proteins. Trace minerals, such as spherules, also contribute to the structure, facilitating protein oligomerization and deposit stabilization. Genetic factors significantly influence drusen biogenesis, particularly polymorphisms in complement regulatory genes. The Y402H variant in the complement (CFH) gene impairs CFH's ability to regulate complement activation and bind to , leading to inefficient clearance of extracellular and increased drusen formation; heterozygous carriers face an of 2.5 for soft drusen development, while homozygotes have an of up to 6.3 compared to non-carriers. This variant accounts for a substantial portion of drusen-associated risk by promoting unchecked and deposit accumulation. At the cellular level, RPE and thickening of act as key precursors to drusen formation. Age-related stiffening and lipid infiltration of hinder nutrient diffusion and waste removal, contributing to RPE dysfunction and the release of lipoproteins into the . These changes create an environment conducive to debris retention and progressive deposit buildup beneath the RPE.

Role in Disease Progression

Drusen play a central role in the progression of by disrupting the (RPE) barrier function, inducing hypoxia, and promoting (CNV). Accumulation of drusen beneath the RPE impairs oxygen and nutrient diffusion from the , leading to relative hypoxia in the subretinal space and subsequent RPE dysfunction through and reduced lysosomal activity. This hypoxic environment activates hypoxia-inducible factor-1α (HIF-1α), upregulating (VEGF) secretion by RPE cells, which drives the formation of fragile, leaky vessels characteristic of neovascular (wet) . Large soft drusen, in particular, elevate the 5-year risk of progression to late up to 47.3% in eyes with bilateral involvement and pigmentary changes. Drusen also serve as a nidus for chronic , exacerbating advancement through release that fosters in dry or CNV in wet . The deposits trigger complement activation and recruitment at the RPE-Bruch's membrane interface, resulting in the local production of pro-inflammatory such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Elevated IL-6 levels correlate with subretinal and progression to , while TNF-α enhances VEGF expression via reactive oxygen species-dependent pathways, further promoting neovascularization. In optic disc drusen, progression involves mechanical compression of retinal ganglion cell axons and vascular compromise within the crowded optic nerve head. The calcified deposits impede axoplasmic flow and directly compress nerve fibers, leading to visual field defects in approximately 71% of affected eyes, often manifesting as enlarged blind spots or nerve fiber bundle defects that worsen with age. Additionally, drusen reduce blood flow to the optic nerve by compressing adjacent vessels, increasing susceptibility to ischemic events such as disc hemorrhages or nonarteritic anterior ischemic optic neuropathy. Recent 2025 research highlights subretinal drusenoid deposits (SDDs) as markers of accelerated progression, with multimodal imaging revealing their association with reduced retinal sensitivity and higher risk stratified by deposit pattern (e.g., ribbon-type SDDs cause greater functional impairment than dot-type). Studies using fundus autofluorescence, reflectance, and have also documented drusen regression following therapy in neovascular cases with submacular hemorrhage, attributed to enhanced macrophage of deposit material.

Clinical Presentation

Symptoms

Drusen, especially macular drusen linked to early age-related (), are frequently asymptomatic in their initial stages, with many individuals unaware of their presence until routine examination. As the condition progresses, patients may report a gradual onset of , characterized by distorted or wavy central vision, or a central , manifesting as a blind spot in the center of the . In contrast, optic disc drusen tend to remain for most patients, though approximately 8-10% experience transient visual obscurations, brief episodes of dimmed or lasting seconds to minutes. Some individuals also report headaches, potentially related to the elevation of the , while rare cases involve hemifield visual loss due to associated field defects. With disease progression, symptoms common to macular drusen include blurred near vision and challenges with low-contrast tasks, such as distinguishing objects in dim or reading small print, though pain is not typically present. These subjective complaints can significantly impact daily activities, with studies showing reduced quality-of-life scores in AMD-associated cases, where over 80% of patients report interference in reading, , or other routine visual tasks.

Ocular Signs

Drusen manifest as distinct ocular signs during fundus examination, varying by location and type. In the , hard drusen appear as small, yellow-white spots less than 63 micrometers in diameter, scattered and well-defined, while soft drusen present as larger, more confluent, dome-shaped elevations greater than 125 micrometers, often pale yellow or grayish-white. Optic disc drusen typically exhibit a lumpy-bumpy elevation of the head with blurred margins, where superficial drusen appear as round, refractile, white or yellow crystalline bodies embedded in the disc substance. Buried optic disc drusen may cause anomalous disc swelling without visible surface deposits, mimicking due to the elevated, hyperemic appearance. Associated findings include (RPE) mottling and pigment clumping surrounding macular drusen, reflecting localized RPE alterations. In optic disc drusen, peripapillary atrophy is common, and hemorrhages—such as , flame-shaped, or subretinal—occur in approximately 2-13% of cases, often resolving spontaneously but indicating potential vascular compromise. Severity is assessed using the modified grading scale, which quantifies drusen area coverage in the (e.g., none, <5%, 5-20%, or >20% of a standard grid circle) to stratify age-related risk. For buried optic disc drusen, B-scan ultrasonography reveals highly reflective echoes with posterior acoustic shadowing, confirming calcification and distinguishing from true edema. Drusen are frequently incidental discoveries during routine eye examinations, detected in 1-2% of cases overall, with bilateral in about 75% of affected individuals and macular drusen often symmetric in early age-related .

Diagnosis

Clinical Examination

Dilated funduscopy remains the gold standard for visualizing superficial drusen, appearing as yellow-white deposits on the retinal surface or during stereoscopic examination, which allows assessment of elevation and depth. For macular drusen, this examination detects early subretinal or sub-RPE deposits, while in , it identifies superficial lumpy excrescences on the disc margin. Visual field testing via perimetry is essential for detecting functional deficits associated with drusen, such as scotomas. In macular drusen cases, the 10-2 pattern perimetry evaluates central sensitivity to identify paracentral scotomas linked to drusen progression in . For optic disc drusen, the 24-2 pattern perimetry assesses peripheral loss, including enlarged blind spots or arcuate defects due to nerve fiber compression. The serves as a simple self-administered test for patients with macular drusen, helping to detect by revealing distortions in straight lines, which indicate central macular involvement. As an ancillary office-based technique, B-scan ultrasonography is particularly valuable for confirming buried not visible on funduscopy, showing highly echogenic material within the disc head with posterior acoustic shadowing.

Imaging Modalities

(OCT) serves as a primary imaging modality for detecting and quantifying macular drusen in (), providing cross-sectional views that reveal drusen as dome-shaped elevations beneath the (RPE) with hyperreflective cores and overlying RPE alterations, such as thinning or disruption. Advanced OCT techniques, including swept-source OCT, enable precise measurement of drusen volume, where volumes exceeding 0.03 mm³ are associated with heightened risk of progression to advanced . These features allow for early identification of high-risk lesions, distinguishing calcified drusen through heterogeneous internal reflectivity and hyporeflective cores that may evolve into atrophic changes. Fundus autofluorescence (FAF) complements OCT by mapping distribution in the RPE, where drusen exhibit variable patterns of hyper-, hypo-, or iso-autofluorescence; hyperautofluorescence often reflects accumulation in active drusen, while hypoautofluorescent areas signal reduced due to RPE degeneration or impairment and may precede . This modality is particularly useful for quantitative assessment, as changes in autofluorescence intensity correlate with drusen regression or growth, facilitating progression tracking in clinical trials with high inter-grader reproducibility. For (ODD), computed tomography (CT) confirms calcification by detecting hyperdense lesions at the posterior globe-optic nerve junction, offering superior sensitivity to MRI, which is less effective for calcified deposits but useful in ruling out compressive etiologies. angiography (OCTA) assesses vascular compression by visualizing peripapillary microvascular attenuation and reduced vessel density, which correlate with thinning and defects in ODD. Enhanced depth imaging OCT further characterizes ODD as hyporeflective masses with hyperreflective borders anterior to the lamina cribrosa. Recent advancements as of 2025 incorporate (AI) into OCT analysis for automated drusen segmentation, particularly enhancing detection of early subretinal drusenoid deposits (SDDs) with classification accuracies exceeding 95% even on limited datasets, improving diagnostic precision and enabling scalable screening.

Management

Monitoring Strategies

Monitoring strategies for drusen in () emphasize regular surveillance to detect progression early, particularly through risk-stratified follow-up protocols tailored to drusen characteristics. For patients with small or hard drusen indicative of early , annual comprehensive eye examinations are typically recommended, though intervals may extend to every 2 years for low-risk cases without symptoms. In contrast, individuals with large or soft drusen, signifying intermediate , require more frequent monitoring, such as semi-annual visits, to assess for structural changes or functional decline. These frequencies align with guidelines that prioritize patients returning every 6 to 24 months based on disease stage, with prompt evaluation for any new visual symptoms suggestive of complications. Optical coherence tomography (OCT) serves as a cornerstone for quantitative monitoring, enabling serial assessment of drusen volume against baseline imaging to identify progression. Drusen volumes exceeding 0.03 mm³ in the central subfield indicate increased risk for late AMD and warrant escalated care. Visual acuity testing and visual field assessments are integrated into these visits, with thresholds like a 2-line loss on Snellen charts or new scotomas prompting intensified surveillance or referral. For high-risk features, including subretinal drusenoid deposits (SDDs), current guidelines such as those from the Royal College of Ophthalmologists recommend OCT monitoring every 4 months, particularly in fellow eyes of those with unilateral advanced disease, to capture subtle changes. Home-based self-monitoring complements clinical visits, with patients instructed to use an daily to detect distortions, blind spots, or indicative of macular changes. This simple tool enhances patient engagement and allows for timely reporting of alterations. during monitoring appointments reinforces modifiable risk factors, integrating advice on —which doubles progression risk if continued—and adoption of a nutrient-rich diet, such as the Mediterranean pattern high in leafy greens and omega-3s, to potentially slow drusen accumulation. These strategies focus on , empowering patients while establishing clear escalation criteria based on objective metrics.

Therapeutic Interventions

Therapeutic interventions for drusen primarily target associated complications rather than the deposits themselves, with approaches varying by type and underlying condition. For drusen linked to age-related macular degeneration (AMD), the Age-Related Eye Disease Study 2 (AREDS2) formulation—containing vitamins C and E, lutein, and zeaxanthin—has been shown to reduce the progression from intermediate to advanced AMD by approximately 25% in patients with intermediate disease characterized by large drusen. These supplements are recommended for individuals with multiple medium-sized drusen or at least one large druse, based on clinical trial evidence demonstrating slowed development of late-stage dry AMD. In cases where drusen-associated dry AMD progresses to neovascular (wet) AMD, anti-vascular endothelial growth factor (anti-VEGF) injections, such as aflibercept, are the standard treatment to inhibit choroidal neovascularization and preserve vision. Aflibercept is typically administered via intravitreal injection at a dose of 2 mg every 4 weeks for the first three doses, followed by dosing every 8 weeks, with adjustments based on clinical response. As of 2025, extended-dosing options like aflibercept 8 mg (EYLEA HD) allow administration every 12-16 weeks after initial doses for neovascular AMD. For optic disc drusen, no direct therapies exist to dissolve or prevent the calcified deposits, as they are generally benign and do not require intervention unless complications arise. Laser photocoagulation is occasionally used for rare complications like (CNV) secondary to , with reported success in stabilizing or resolving the neovascularization in select cases, though it is not routinely recommended due to risks of damage. Emerging therapies as of 2025 show promise for drusen regression in . Subthreshold treatment, such as nanosecond , has demonstrated potential reductions in drusen volume and slowing of progression in clinical trials for intermediate , without visible burns. As of 2025, therapies targeting complement (CFH), a key genetic for drusen accumulation, remain in phase II trials (e.g., GEM103), with data suggesting potential to slow drusen buildup in dry patients by modulating complement pathway overactivation. Surgical options focus on complications rather than drusen directly; is performed for epiretinal membranes associated with drusen-related traction, involving removal of the vitreous gel and membrane peeling to improve macular distortion and vision. Drusen removal itself is not indicated, as it offers no proven benefit and carries surgical risks. Monitoring strategies guide the timing of these interventions by detecting early complications like neovascularization.

Prognosis

Progression Risks

The size and area of drusen are key predictors of progression to late-stage age-related (). Large drusen, defined as those exceeding 125 μm in , significantly elevate the risk, with data from the Age-Related Eye Disease Study (AREDS) indicating approximately a 4-fold increase in the likelihood of developing advanced over 5 years compared to eyes with smaller drusen. Very large drusen (>250 μm) confer a higher 5-year risk of about 25%. This risk escalates further when drusen occupy a substantial macular area, such as greater than half a disc area, correlating with heightened susceptibility to or neovascularization. Certain biomarkers further stratify progression risks in patients with drusen. Elevated levels of (CRP), a marker of , are independently associated with accelerated advancement, with concentrations above 3 mg/L linked to approximately 50% increased risk ( 1.5) of developing compared to levels below 1 mg/L. Similarly, drusen regression observed on (OCT) signals a poor , often preceding the onset of as the regressing drusen give way to loss and outer retinal atrophy. Comorbidities involving drusen distribution and genetic background amplify progression odds. Bilateral drusen presence roughly doubles the risk of advancing to late over 5 years relative to unilateral involvement, particularly when combined with pigmentary changes, yielding up to a 47% progression rate. A family history of adds a 1.5- to 3-fold increased risk, reflecting shared genetic factors that influence drusen accumulation and subsequent degeneration. Recent 2025 analyses highlight the presence of subretinal drusenoid deposits (SDDs) in patients with , similar to other populations; SDDs generally predict faster transition to compared to conventional drusen phenotypes.

Long-Term Outcomes

In patients with drusen associated with age-related (), approximately 70-80% maintain good (20/40 or better) over the long term through regular monitoring and lifestyle interventions. However, around 20% of cases progress to legal blindness within 10 years, primarily due to advancement to late-stage . Key complications include the development of in 15-20% of eyes with large drusen over 5-10 years, leading to gradual central vision loss, and neovascular in about 10% of cases, which can cause more abrupt visual decline if untreated. For optic disc drusen, which are distinct from retinal drusen, defects are common, affecting up to 87% of adults, with slow progression (approximately 1.6% per year) in those with visible drusen, often manifesting as blind spot enlargement or arcuate defects. Drusen themselves carry no direct link to increased mortality, but the associated advanced elevates fall risk by twofold in elderly individuals due to impaired vision and mobility. As of 2025, early intervention strategies, including therapies for neovascular complications and nutritional supplements for dry AMD, have contributed to an approximately 19% reduction in AMD-related blindness prevalence globally from 2000 to 2020 by slowing progression and preserving vision in at-risk patients. Complement inhibitors like and , approved in 2023, slow growth by approximately 20-30%, further improving outcomes. Monitoring and timely therapeutic interventions play a crucial role in optimizing these outcomes.

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