Introduction

Drusen remains one of the main biomarkers of age-related macular degeneration (AMD). They play a prognostic role and reflect the stage of the disease. Distinguishing drusen parameters provides a personalized risk profile for the transition to geographic atrophy or neovascular AMD. Everyone working with AMD patients should know how to detect, quantify, and track drusen on OCT.

What are the types of drusen?

Drusen are accumulations of pathological material of lipid-protein nature, localized under the PES. They reflect impaired transport and exchange between the retinal pigment epithelium and Bruch’s membrane. Historically, they are divided into hard, soft, reticular pseudodruses (or subretinal drusenoid deposits) and other less common types (confluent, pachidruses) as well as other retinal OCT biomarkers for drusen segmentation.

Hard drusen

On ophthalmoscopy, they are small, rounded, clearly delineated foci of yellowish-white color. On OCT, they look like local deposits of hyperreflective material under the PES with a diameter of no more than 63 microns. In small quantities (up to 8), they are not a sign of pathology. They are asymptomatic in most patients.

Soft drusen

Soft drusen are larger than hard drusen and appear as extensive foci with blurred edges on the fundus. On OCT, they are dome-shaped and elevated above the PES and are divided into medium (63-125 μm) and large (more than 125 μm) in size. They are more strongly associated with AMD progression, especially when accompanied by pigmentary abnormalities and other OCT biomarkers (hyperreflective foci, destruction of the ellipsoidal zone, etc.). Soft drusen can enlarge and merge. An area of ​​merging drusen with a diameter exceeding 350 μm is called a drusenoid detachment of the PES.

Soft drusen detected by Altris IMS. AI models are for Research Use Only. Not for use in diagnostic purposes. 

Confluent drusen

These are multiple small deposits under the PES, which can occur in relatively young patients; on FAG they often show a “starry sky” appearance. On OCT, there are multiple small symmetrical elevations of the PES, small in diameter (like hard drusen), but more numerous, prone to merging. The course is variable: some patients maintain a stable course for years, some have an increased risk of complications and transition to the late stages of AMD.

Reticular pseudodrusen (or subretinal drusenoid deposits)

They differ fundamentally in their localization, being located above the PES (in the subretinal space). They contain some common proteins with soft drusen, but differ in lipid composition. Due to their close location to the important photoreceptor layer, they are more often combined with a decrease in visual function, and also carry a higher risk of progression to late AMD (especially characterized by a rapid transition to geographic atrophy (GA) and the development of macular neovascularization (MNV) type 3).

What are the levels of drusen?

The AREDS size classification is still useful in clinical practice: small <63 μm, medium 63–124 μm, large ≥125 μm. Analyses confirm that the 5-year risk of progression to late AMD increases with the number and size of drusen in both eyes and especially with the presence of reticular pseudodrusen. In the NICE guidance for the management of patients with AMD (2018), the risk of progression also depends on the size and type of drusen, as well as the presence of associated pathological changes (pigmentary abnormalities, vitelliform deposits).

The OCT era has added powerful quantitative metrics with AI for drusen measurement and monitoring:

• drusen height (μm),
• area (mm²),
• volume (mm³),
• topography (central ring within 1.5 mm; parafovea 3–5 mm),
• dynamics of changes and associated biomarkers (hyperreflective foci, ellipsoidal zone disruption, presence of hypertransmission zones, etc.).

A practically significant increase in the volume of drusen in the macular region over a year/two correlates with structural and functional deterioration (destructive changes in the photoreceptor layer, changes in ONL thickness, visual acuity). Data from multicenter projects (such as MACUSTAR) confirm the repeatability of measurements and the possibility of comparison between devices, provided that the correct algorithms are used.

What do drusen look like on OCT?

On B-scan OCT, classic hard and soft drusen are localized deposits of hyperreflective material between the PES and Bruch’s membrane (under the PES). Reflectivity can be uniform or heterogeneous depending on the structure and stage of development. Reticular pseudodruses are localized between the photoreceptor layer and the PES (above the PES) – this is the key difference from conventional drusen. On OCT images, they appear as tubercles in the subretinal space that remodel the outer layers of the retina (in particular, the ellipsoidal zone), and on en face, they are visualized as punctate structures, usually connected in a mesh pattern.

A: Soft drusen. B: Hard drusen (Source) Another classic white and black scan

In addition to the drusen themselves, clinically significant are hyperreflective foci, destruction of the ellipsoidal zone, thinning of the outer layers/ONL, formation of hyperreflective foci in OCT or geographic atrophy with the effect of hypertransmission – it is the combinations of these features that form prognostic models of the transition of intermediate AMD to late stages. The combination of these biomarkers consistently exceeds single morphometric thresholds.

En Face Optical Coherence Tomography Illustration of the Trizonal Distribution of Drusen and Subretinal Drusenoid Deposits in the Macula (Source)

As we can see, en face and linear OCT scans help to differentiate different types of drusen and track their progression dynamics. Modern deep learning models for AI drusen examination and en face analysis, like Altris.AI, reliably detect and segment classic drusen from subretinal drusenoid deposits, improving repeatability and reporting speed. You may see the difference from the classic white and black image analysis here:

Confluent drusen are highlighted by Altris IMS. AI models are used for Research Use Only. Not for use in Diagnostic Purposes. 

How to measure drusen size?

Here we can find how drusen are measured:

1) Classical size scale (AREDS):

Orientation on diameter or equivalent on planar reconstructions: <63, 63–124, ≥125 μm. Convenient, but does not take volume/height or topography into account.

2) Quantitative OCT analysis of PES elevation:

On ZEISS CIRRUS instruments, the Advanced RPE Analysis module automatically calculates the area and volume of PES elevation in standard 3 and 5 mm rings around the fovea; the minimum height that the system consistently includes in quantitative results is about 19–20 μm. This provides repeatable metrics and a common “language of numbers” for clinical and research purposes.

3) Morphometric rule for differentiation of drusen and drusenoid detachment of PES:

By basal width: <350 μm – drusen, ≥350 μm drusenoid detachment of PES.

4) AI segmentation and 3D morphometry:

Deep networks segment Bruch’s membrane, PES, and ellipsoidal zone, as well as PES elevation on OCT, calculating drusen height/area/volume and generating dynamics maps. Validation work in 2023–2025 will demonstrate robustness between different OCT devices, which is critical for multicenter networks. Besides, you may track drusen progression on OCT AI tool and stay informed ahead of time to prevent more severe pathology changes in advance.

Can drusen exist without macular degeneration?

Yes, and this is possible in the following cases.

Small (<63 μm) single drusen may occur in the elderly in the absence of other signs of AMD and concomitant risk biomarkers (hyperreflective foci, ellipsoidal zone abnormalities). In this phenotype, the 5-year risk of progression is low; routine monitoring at an interval of 1 time per year is sufficient, if possible, with recording quantitative indicators on OCT (volume/area of ​​PES elevation) for comparison in dynamics. The patient should be informed that the fact of “small drusen” alone does not equal a diagnosis of AMD and does not require treatment, but it is advisable to maintain lifestyle modification (blood pressure control, smoking cessation, a healthy diet).

Confluent drusen are sometimes found in younger patients; they do not always fit into the classic models of AMD. Tactics – individual observation with an emphasis on high-quality OCT documentation (the same scan and control of concomitant biomarkers). In the absence of “red flags”, a 6-12 month follow-up interval is sufficient.

Understanding Macular Degeneration (Source)

Hereditary dystrophies (EFEMP1-related; associated phenotypes are Doyne’s cellular degeneration of the retina and Leventis’ malady) form drusen-like deposits without the typical pathogenesis inherent in AMD. They have an autosomal dominant inheritance pattern and are characterized by yellow-white deposits, like drusen, accumulating under the PES, often in the peripapillary zone. The clinical picture may include gradual vision loss, impaired contrast sensitivity, or metamorphopsia. In this case, timely detection of the phenotype (age of onset, family history, symmetry, characteristic fundus appearance) and referral for medical and genetic counseling with a subsequent individual follow-up plan, including monitoring of possible complications (neovascularization, atrophic changes).

Drusen vs. drusenoid detachment of PES

Drusen are local elevations of PES above Bruch’s membrane due to deposits of pathological material under PES. Usually multiple, of different diameters, with a tendency to merge with the formation of larger, topographically continuous areas of PES elevation.

Drusenoid detachment of the pigment epithelium is formed from a larger conglomerate of drusenoid material, which in turn is formed as a result of the fusion of drusen.

Another differentiating drusen and drusenoid deposits subtypes on multimodal imaging samples

On B-scan OCT, it has smooth edges, uneven reflectivity, and often retains communication with neighboring drusen. On en face visualization, a conglomerate of elevation is visible, which corresponds to the zone of changes in the PES-Bruch’s membrane complex. In the absence of fluid inside the lesion, we are talking about drusenoid detachment of PES; if homogeneous hyporeflectivity is visualized under PES, this is serous detachment of PES, and if there are signs of a neovascular membrane according to OCTA or FAG, this is fibrovascular detachment of PES. Therefore, in doubtful cases, it is advisable to add OCTA to exclude hidden MNV.

The main morphometric rule: basal width ≥350 μm (in the horizontal projection of the OCT slice favors drusenoid detachment of PES. In some situations, we also pay attention to the content (serous/optically empty space, signs of vascularization), PES profile, and associated biomarkers, since PES detachment is more often associated with the risk of transition to HA or the formation of neovascularization.

What is the best treatment for drusen?

Drusen are not treated as a separate nosology. They are a structural biomarker of AMD, and also have prognostic value for assessing the further development and rate of progression of the disease.

Optimal tactics for detecting drusen:

Optimal tactics for detecting drusen may include the following

Risk modification: 

• smoking cessation,
•  blood pressure control,
• metabolic profile,
• diet.

Dietary supplements based on AREDS 2: 

• taking antioxidant complexes (lutein, zeaxanthin, vitamins C and E, zinc, copper) reduces the risk of transition to late AMD by approximately 25% within 5 years (according to AREDS 2).

Quantitative monitoring on OCT: 

• record the volume/area/height of drusen and their dynamics, distinguish between drusen types, detect other concomitant signs of AMD progression (hyperreflective foci, destructive changes in the ellipsoidal zone, pigmentary anomalies, vitelliform material deposition, signs of formation of foci of geographic atrophy).
• Individualize observation intervals (depending on the type of drusen, the dynamics of their structural changes and other risk factors).
• Among the new promising methods of treating dry AMD at the drusen stage is multiwavelength photobiomodulation.

Multiwavelength photobiomodulation:

This method is aimed at stopping or regressing the progression of dry AMD by modulating mitochondrial activity and consists of the use of specific light (red and near-infrared spectrum from ~590 to 850 nm), which can reduce oxidative stress in retinal cells, inflammation and apoptosis of PES cells.

The efficacy as a potential treatment approach has remained controversial until recently: studies have shown only temporary improvement in visual function and reduction in drusen volume (not maintained for 6 months).

Updated data from the LIGHTSITE III study were presented at the ARVO 2025 conference. They showed that photobiomodulation can significantly slow the decline in visual acuity and reduce the rate of expansion of HA zones

Recently, the FDA approved photobiomodulation for the treatment of AMD.

For complications:

• Neovascular AMD– anti-VEGF.

• Geographic atrophy – injectable drugs (inhibitors of the C3 and C5 complement system), approved by the FDA

The role of AI drusen quantification OCT

The role of AI: automated drusen-volume measurement in OCT is now a reality. IT allows automated segmentation and counting (3D volume, area, height), identification of reticular pseudodruses and other signs of AMD, and compilation of prognostic profiles.

In practice, applying an OCT drusen-counting algorithm reduces variability in assessments and helps personalize visit frequency. Additionally, home OCT monitoring models with AI analysis are being developed, indicating that broader AI support for AMD is fast approaching.

Conclusion

Drusen on OCT are more than just a sign of AMD. They have become one of the most important biomarkers of age-related macular degeneration and a kind of “compass” in the daily practice of an ophthalmologist. Today we understand that:

Drusen come in different types, and, accordingly, carry different prognostic information: hard, soft, confluent, and reticular pseudodrusen. Each type carries a different risk and requires a different surveillance strategy.

Drusen levels are no longer limited to diameter, height, volume, dynamics, and structural features as well as accompanying OCT biomarkers have also become important. It is the combination of these parameters that allows us to predict the transition to the late stages of AMD.

OCT has changed the game: drusen can now be seen in 3D, segmented automatically, build PES elevation maps, and compare data between visits. Thanks to this, the doctor receives a lot of information about the evolution of the disease.

AI sets a new standard: algorithms can accurately calculate drusen volume, identify their subtypes, generate prognostic profiles, and reduce interobserver variability. This translates data from subjective descriptions into objective, reproducible numbers.

Drusen classification on OCT using AI allows not only ascertaining the presence of drusen, but also differentiating their type, objectively measuring their number and parameters, and tracking their dynamics via AI drusen quantification on OCT. For the doctor, this means identifying risk factors in the early stages of retinal disease, accurately comparing data between visits, and prescribing the correct therapy promptly.

Home monitoring is the future that has already begun: the first FDA-approved solutions with “OCT + AI” are currently used to monitor fluid in neovascular AMD, but they pave the way for daily structural monitoring of drusen as well. This means that in the near future, the patient may be able to monitor their own retina at home, and the doctor may be able to see the dynamics in real time.

In the treatment of drusen wet or dry AMD, the main goal remains not to “remove drusen,” but to minimize risks (smoking, diet, systemic factors), prescribe AREDS2-based complexes, timely detect complications, and apply already available therapies (anti-VEGF in INM, C3 and C5 inhibitors of the complement system in HA). Among the new promising methods for treating dry AMD at the drusen stage is multiwavelength photobiomodulation.

 

It is important to remember when communicating with the patient: drusen is not a therapeutic target, but a structural “compass”. We do not “treat drusen.” Instead, we systematically reduce risks (smoking, blood pressure, nutrition), use drugs based on the AREDS2 formula, and most importantly, we regularly measure their quantitative parameters in dynamics. When complications appear and the transition to a late stage occurs, we prescribe treatment based on the same objective OCT metrics. Thus, instrumental accuracy and AI analytics turn drusen into a manageable marker that helps to timely detect the risks of AMD progression.

Thus, drusen on OCT have become a bridge between morphology and prognosis. They provide an opportunity to build a long-term strategy for preserving vision. Today, the doctor is required not only to see drusen, but also to quantitatively measure, assess in dynamics, calculate the risk, and explain to the patient his individual risks. It is thanks to these approaches that we are moving towards a new paradigm – personalized ophthalmology, where decisions are made based on objective digital data, enhanced by artificial intelligence.

Sources:

1. 1. https://pubmed.ncbi.nlm.nih.gov/39558093/
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   5. https://www.ophthalmologyscience.org/article/S2666-9145(25)00182-4/fulltext
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   7. https://www.ophthalmologytimes.com/view/arvo-2025-update-on-the-lightsite-iii-study-in-amd