The clinical importance of phenotyping drusen

A 42-year-old lady presented to the outpatient department with diminished vision for near, for one year. Best-corrected visual acuity was 6/9 N8 in both eyes. The anterior segment was within normal limits. Fundus examination showed bilateral, nearly symmetrical, medium-to-large drusen along with deposition of yellowish amorphous material in the center of the macula. Numerous drusen, which were smaller and more discrete, were seen in the temporal macula extending to the superior arcades as well Fig. 1a and b. Fundus fluorescein angiography (FFA) showed discrete hyperfluorescent lesions with a starry-sky appearance, corresponding to the drusen in the arteriovenous phase. There was central blocked fluorescence due to the vitelliform material Fig. 1c and d. Optical coherence tomography (OCT) showed sub-retinal pigment epithelium (sub-RPE) elevations with a classical saw-tooth pattern. Diffuse, homogenous sub-retinal hyperreflective material (SHRM) with back shadowing was seen, limited to the foveal and parafoveal region Fig. 2a and b. The autofluorescence (BAF) showed hyperautofluorescence (hyper-AF) corresponding to the SHRM. This was consistent with acquired vitelliform lesions (AVLs) Fig. 2c and d. Indocyanine green angiography (ICGA) and OCT angiography did not show macular neovascularization (MNV).Figure 1: (a and b) Color fundus photograph of both eyes showing medium-to-large drusen at the macula and extending to the superior and temporal paramacular region. There was yellowish amorphous material at the center of the macula, suggestive of acquired vitelliform lesions. (c and d) On FFA, numerous discrete hyperfluorescent dots corresponding to the cuticular drusen were seen in the macular area in the arteriovenous phase. FFA = Fundus fluorescein angiographyFigure 2: (a and b) OCT showing saw-tooth appearance of type 2 cuticular drusen (yellow arrow). Diffuse, homogenous SHRM with back-shadowing suggestive of AVL (orange arrow). (c and d) The SHRM corresponded to the central hyper-AF seen on BAF. AF = autofluorescence, AVL = acquired vitelliform lesion, BAF = blue autofluorescence, OCT = Optical coherence tomography, SHRM = Sub-retinal hyperreflective materialWhat would you do Next? Inject anti-vascular endothelial growth factor (VEGF) – loading doses followed by pro-re-nata regimen Photodynamic therapy (PDT) Laser photocoagulation Age-related Eye Disease Study (AREDS) 2 formula. Diagnosis Cuticular drusen. Answer D. AREDS 2 formula Discussion Gass first described cuticular drusen as small, yellow, sub-retinal lesions that have a typical starry-sky appearance seen best in the arteriovenous phase of FFA.1 The level of the drusen has since been better characterized by OCT as between the basal lamina of the RPE (RPE-BL) and the inner collagenous layer of Bruch’s membrane. There is a strong female preponderance, especially in those complicated with AVL and neovascularization.2 Clinically, cuticular drusen appear as roundish yellow lesions, measuring about 50–75 micrometers (µm), clustered in the macular area and/or mid-peripheral retina. When they coalesce, they resemble soft drusen. Cuticular drusen are confirmed by characteristic features on at least three out of four imaging modalities, including color fundus photographs, OCT, FFA, and Fundus autofluorescence (FAF). Balaratnasingam et al.3 described three distinct patterns on OCT. Type 1 pattern: Shallow RPE-BL elevations without discernible drusen content. Type 2 pattern: Classical saw-tooth configuration with hyporeflective internal content. Type 3 pattern: Broad, mound-shaped RPE-BL elevations with hyporeflective internal content. Type 3 pattern is common and seen in up to 60% of cases. FFA depicts the classical “starry-sky appearance” with several round hyperfluorescent lesions that remain hyperfluorescent for the entire duration of FFA. ICGA shows early hyperfluorescent lesions surrounded by hypofluorescent halos, which later become hyperfluorescent. The lesions on FFA are much more numerous than those on ICGA. FAF pattern of drusen is characterized by central hypoautofluorescence with a hyperautofluorescent rim. In our case example, this pattern was obscured by the hyper-AF due to AVL. AVLs are typically seen in younger age, as seen in our patient. They are seen as diffuse, homogeneous SHRM on OCT and are hyper-AF on blue FAF.2,3 AVL can lead to the development of MNV; however, the MNV may be obscured by the back shadowing on OCT and have blocked fluorescence on angiography. Resolution of AVL heralds the onset of RPE abnormalities, drusen disappearance, and geographic atrophy.3 Treatment with anti-VEGF is indicated only once MNV develops. Laser treatment and PDT are not recommended in view of the risk of worsening RPE damage. Age-related Eye Disease Study (AREDS) 2 formula—containing antioxidants and zinc—may help reduce the risk of progression to late Age related macular degeneration (AMD) in patients with extensive drusen, regardless of drusen subtypes.4 AVLs should not be confused with SHRM due to activity from MNV. Multimodal imaging is essential to characterize drusen subtypes, make the distinction between neovascular and non-neovascular pathologies, and withhold unnecessary anti-VEGF injections. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest.