History of drusen presents to retina clinic for second opinion
Patient reports decreased vision and distortion of vision in right eye
Exam Findings
BCVA: 20/60 OD; 20/25 OS
IOP 19 OU
Pupils: Round, reactive, no rAPD
SLE OU: trace NSC and anterior syneresis
DFE OU:
Figure 1: Fundus photographs of right and left eye showing confluent soft drusen and pigmentary changes within the macula.
Figure 2:(A) OCT macula of the right eye showing large central pigment epithelial detachment (PED) with hyperreflective material beneath RPE and adjacent drusenoid PEDs. No intra- or subretinal fluid observed. Normal choroid (B) OCT macula of left eye with similar findings as right eye with smaller central PED.
Differential Diagnosis of Chorioretinal Conditions with Pigment Epithelial Detachments (PED)
Age-Related Macular Degeneration
Central Serous Chorioretinopathy
Polyploidal Choroidal Vasculopathy
Subtypes of PED
Drusenoid
Serous
Fibrovascular
Hemorrhagic
Additional Investigations
Ancillary testing to determine whether choroidal neovascularization is present
Figure 3: Fluorescein angiography of right eye at initial presentation. (A) Late arterial or early laminar phase with hypofluorescent rim (indicating hypopigmentation or RPE atrophy) surrounding hyperfluorescent center (suggesting pigment clumping). (B) Arteriovenous transit phase without leakage. (C) Late phase with staining within PED without leakage (hot spots or plaques).
Figure 4: Indocyanine green angiography of right eye showing irregular scalloped borders of drusenoid PED at initial presentation. Hypofluorescent during early and late frames suggesting that choroidal neovascularization (CNV) is not present.
Figure 5: Figure 5: OCT Macula at eight-month follow-up. (A) Right eye with larger central drusenoid PED with vitelliform lesions at PED apex. (B) Left eye with enlarging central drusenoid PED with vitelliform lesions at top of apex with possible subretinal fluid.
Three years after initial presentation s/p intravitreal Eylea x3 and Lucentis x1 OD and Lucentis x1 OS. Visual acuity: 20/50 OD and 20/80 OS
Figure 6: Fundus photograph of both eyes showing increased pigmentary changes (hyperpigmentation in macula).
Figure 7: OCT macula. (A) Right eye showing PED collapse with pockets of intraretinal fluid overlying PED and intraretinal RPE migration. (B) Left eye showing PED with red asterisk indicating focal RPE disruption (possible RPE aperture).
Figure 8:(A) Fluorescein angiography of left eye showing late staining of drusen, no leakage, and window defect temporal to macula (blue arrow) (B) ICG of left eye showing no clear CNV and window defect temporally (blue arrow).
Diagnosis
Non-neovascular AMD (intermediate AMD) with bilateral drusenoid PED
Eight months: Bilateral enlargement of bilateral PED with possible appearance of subretinal fluid on OCT Macula without CNV see on FA/ICG and unresponsive to anti-VEGF therapy
Three years: Collapse of PED with focal RPE atrophy suggesting RPE aperture without clear CNV
Pathophysiology of AMD
Metabolic disorder of RPE and photoreceptors
Accumulation of granular lipid rich material between plasma and basement membrane of RPE (basal laminar deposits)
Accumulation of lipofuscin deposits in Bruch’s membrane (basal linear deposits or soft drusen)
Progressive accumulation of lipids creates a hydrophobic environment
RPE pumping becomes stressed causing accumulation of fluid and debris leading to RPE detachment from Bruch’s
Treatment (AAO Practice Guidelines for Non-Neovascular AMD)
Smoking cessation
Monitoring with Amsler Grids
AREDS2: intermediate AMD or advanced AMD in one eye
Close monitoring for CNV with multimodal imaging studies (FA, ICG, OCT, OCT-A)
Prognosis and Future Directions
Drusenoid PEDs associated with non-neovascular AMD (especially intermediate rather than high-risk AMD)
Better visual prognosis than other PEDs
Subset of Age Related Eye Disease (AREDS) Study #28
5 percent prevalence of drusenoid PEDs within study
At median of eight years, 42 percent of patients developed advanced AMD with 19 percent developing geographic atrophy and 23 percent neovascular AMD
Patients usually experience decline in visual acuity (loss of 26 letters from 20/30 to 20/60)
In comparison, original AREDS study showed that risk of progressing from intermediate to advanced AMD over five years, 6 percent with one eye involvement and 26 percent with two eye involvement
Life cycle of drusenoid PED
Drusenoid PED usually develop and enlarge on background of large confluent soft drusen and hyperpigmentation
Collapse of PED through unknown mechanism
Development of hypopigmentation
Final phase: central geographic atrophy
References
Roquet W, Roudot-Thoraval F, Coscas G SG. Clinical features of drusenoid pigment epithelial detachment in age related macular degeneration. Br J Ophthalmol. 2004;88:638-43.
Tan, A; Simahae, D; Balaratnasingam, C; Dansingani, K; Yannuzzi LA. A Perspective on the Nature and Frequency of Pigment Epithelial Detachments. Am J Ophthalmol. Elsevier Inc.; 2016;172:13-27.
Querques G, Capuano V, Costanzo E, Corvi F, Querques LEA, Introini UGO, et al. Retinal Pigment Epithelium Aperture: A Previously Unreported Finding in the Evolution of Avascular Pigment Epithelium Detachment. Retina. 2016;36(12):65-72.
Mrejen S, Sarraf D, Mukkamala SRIK. Multimodal Imaging of Pigment Epithelial Detachment: A Guide to Evaluation. Retina. 2013;33:1735-62.
Zayit-soudry S, Moroz I, Loewenstein A. Retinal Pigment Epithelial Detachment. Surv Ophthalmol. 2007;52(3):227-43.
Amd NE, Amd I, Bressler SB, Bressler NM. Age-Related Macular Degeneration. Fifth Edit. Retina. Elsevier Inc.; 2000. 1150-1182 p.
Sikorski BL, Bukowska D, Kaluzny JJ, Szkulmowski M, Kowalczyk A, Wojtkowski M. Drusen with Accompanying Fluid. Ophthalmology. Elsevier Inc.; 2011;118(1):82-92.
Contact
Amir Kashani, MD, PhD, Assistant Professor of Clinical Ophthalmology, ahkashan@med.usc.edu
