True or pseudo optic disc edema: clinically-based approach to the differential diagnosis.

PURPOSE: To present a clinically based approach to the differentiation of optic disc edema (DE) cases, commonly seen in neuro-ophthalmology. METHODS: Consecutive patients who were considered to have unilateral or bilateral DE during examinations in the outpatient clinic and were referred to the neuro-ophthalmology department were included in this prospective study. The examination findings and differential diagnosis based on clinical signs and symptoms, and neuro-ophthalmological approach were evaluated in cases of DE. RESULTS: Of the 119 cases with DE, 69 (58%) were women and 50 (42%) were men, where 89 (75%) had true optic DE (ODE) and 30 (25%) had pseudo optic DE  (PODE). Non-arteritic anterior ischemic optic neuropathy (n = 40), increased intracranial pressure (n = 32), and anterior optic neuritis (n = 17) were determined as the causes of true ODE, whereas small and crowded optic disc (n = 12), tilted optic disc (n = 8), myelinated nerve fibers (n = 5) and optic disc drusen (n = 5) as the causes of PODE. Patients with optic neuritis were the youngest (28.41 years) group of ODE cases while those with non-arteritic anterior ischemic optic neuropathy were the oldest (59.98 years). The first symptoms were sudden and painless loss of vision and/or visual field in cases with non-arteritic anterior ischemic optic neuropathy, pain increasing with eye movements and loss of vision and/or visual field in cases with optic neuritis, headache, and from time to time blurred vision in cases with increased intracranial pressure. Patients having vision loss due to amblyopia constituted (30%) of PODE cases while 70% were determined incidentally and they had the best visual acuity. The accuracy of the preliminary diagnosis based on neuro-ophthalmologic examination findings was 79% in all cases. CONCLUSION: Detailed history taking and neuro-ophthalmological examination are essential in the differential diagnosis of ODE and PODE.

Prevalence, time course, and visual impact of peripapillary hyperreflective ovoid mass-like structures (PHOMS) in pediatric patients with optic nerve pathologies.

BACKGROUND: Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are a recently defined optical coherence tomography (OCT) finding. The purpose of this study was to characterize the presence of PHOMS and their visual significance in pediatric patients with and without optic nerve pathologies. METHODS: This retrospective study evaluated 400 patients (<18 years of age) including normal control subjects and patients with optic neuritis, papillitis, optic nerve head drusen (ONHD), and papilledema. Information on demographics, visual function, and structural parameters were obtained. RESULTS: PHOMS were found in 7 of 258 normal control eyes (2.7%), 9 of 59 eyes with optic neuritis (15.3%), 58 of 76 eyes with ONHD (76.3%), 3 of 11 eyes with papillitis (27.3%), and 180 of 308 eyes with papilledema (58.4%). PHOMS were more prevalent in the papilledema (P < 0.001), ONHD (P < 0.001), and optic neuritis (P = 0.028) eyes than in control eyes. We identified 5 cases where PHOMS developed de novo. This occurred over an average of 2.3 years (range, 0.2-7.4 years). Sixteen cases of PHOMS resolved over an average of 1.1 years (range, 0.3-4.0 years). Cross-sectionally, PHOMS were not associated with visual acuity (P = 0.551), retinal nerve fiber layer thickness (P = 0.068), ganglion cell volume (P = 0.375), or visual field mean deviation (P = 0.795). CONCLUSIONS: PHOMS are present in a majority of children with papilledema or ONHD. PHOMS are dynamic and may form de novo over time with optic nerve pathology and may resolve either through treatment or atrophy. There was no relationship between the presence of PHOMS and poor visual function in our study cohort.

Diagnostic dilemma of papilledema and pseudopapilledema.

BACKGROUND: Papilledema is the optic disc swelling caused by increased intracranial pressure (ICP) that can damage the optic nerve and cause subsequent vision loss. Pseudopapilledema refers to optic disc elevation without peripapillary fluid that can arise from several optic disc disorders, with optic disc drusen (ODD) being the most frequent cause. Occasionally, pseudopapilledema patients are mistakenly diagnosed as papilledema, leading to the possibility of unneeded procedures. We aim to thoroughly examine the most current evidence on papilledema and pseudopapilledema causes and several methods for distinguishing between both conditions. METHODS: An extensive literature search was conducted on electronic databases including PubMed and google scholar using keywords that were relevant to the assessed pathologies. Data were collected and then summarized in comprehensive form. RESULTS: Various techniques are employed to distinguish between papilledema and pseudopapilledema. These techniques include Fundus fluorescein angiography, optical coherence tomography, ultrasonography, and magnetic resonance imaging. Lumbar puncture and other invasive procedures may be needed if results are suspicious. CONCLUSION: Papilledema is a sight-threatening condition that may lead to visual affection. Many disc conditions may mimic papilledema. Accordingly, differentiation between papilledema and pseudopailledema is crucial and can be conducted through many modalities.

Validation of retinal oximetry vessel selection using fluorescein angiography in patients with optic disc drusen.

Retinal oximetry could provide insights into the pathophysiology of optic nerve disease, including optic disc drusen (ODD). Vessel selection for oximetry analysis is based on morphological characteristics of arterioles and venules and supported by an overlay of estimated blood oxygen saturations. The purpose of this cross-sectional study was to determine the validity of this vessel selection procedure by comparing it with vessel selection supported by video fluorescein angiography (FA). The study included 36 eyes of 36 patients with ODD who underwent retinal oximetry (Oxymap retinal oximeter T1) followed by FA (Heidelberg Spectralis). Two trained graders selected vessel segments in a pre-defined measurement area around the optic disc. One of these graders additionally performed the vessel segment selection with the support of FA images. When performed by the same grader, FA-supported and non-FA-supported vessel selection did not lead to significant differences in total vessel segment length, estimated oxygen saturations or vessel diameters (all p > 0.05). Inter-grader differences were found for arterial and venous segment lengths and arterial saturation (p < 0.05). A similar tendency was found for the arteriovenous saturation difference (p = 0.10). In conclusion, identifying vessel segments for retinal oximetry analysis based on vessel morphology and supported by a color-coded saturation overlay appears to be a valid method without the need for invasive angiography. A numerically small inter-grader variation may influence oximetry results. Further studies of retinal oximetry in ODD are warranted.

Kinetic and static perimetry after 16 years and additional OCT-A analysis in eyes with long-lasting optic disc drusen.

The aim of the study is to evaluate the progression of visual field (VF) defects over 16 years of observation and to assess abnormalities in vessels and retinal nerve fibre layer (RNFL) thickness in patients with optic disc drusen (ODD). Both static automated perimetry (SAP) and semi-automated kinetic perimetry (SKP) were performed in 16 eyes of 8 patients (mean age 54 years) with ODD among 26 eyes of 13 patients examined 16 years before. The area of I2e, I4e, III4e, and V4e isopters was measured in deg2. The MD and PSD parameters were estimated using SAP. Optical coherence tomography angiography (OCT-A) was additionally performed in 16 ODD eyes and 16 eyes of 8 healthy subjects to estimate the RNFL thickness and vessel density of the optic nerve disc and the macula. The differences in all isopter areas of SKP and SAP parameters after 16 years were not significant. The analysis of OCT-A showed a significant reduction of the vessel density and RNFL of the peripapillary area in each segment in patients with ODD, compared with the control group. The highest reduction of RNFL was observed in the superior segment of the optic disc area (92.56µm vs 126.63µm) also the macular thickness was decreased in ODD patients, compared with the control group. In the macula, there was a significant vascular defect in the whole superficial layer and in the parafoveal deep layer. A strong significant correlation of the parafoveal deep plexus with MD and PSD parameters was detected. In conclusion, VF loss due to ODD after 16 years of the follow-up was not significant both in SKP and SAP. ODD caused a reduced vessel density and RNFL, as well as macular thickness in OCT-A. SAP parameters were influenced by parafoveal deep plexus.

Updates on ophthalmic imaging features of optic disc drusen, papilledema, and optic disc edema.

PURPOSE OF REVIEW: Optic nerve head elevation can be associated with vision loss. This review provides an update regarding key features of optic disc drusen (ODD) compared with papilledema from increased intracranial pressure and optic disc edema from other causes. RECENT FINDINGS: Clinical history and funduscopic examination are not sufficient to correctly diagnose different causes of optic nerve head elevation. Multimodal ophthalmic imaging is noninvasive and should be used as first-line diagnostic testing to distinguish optic disc edema or papilledema from pseudoedema. Advanced ophthalmic imaging, including enhanced depth imaging optical coherence tomography (EDI-OCT) and autofluorescence imaging, can visualize ODD at high resolution and determine whether there is optic disc edema. OCT angiography does not require contrast and can rapidly visualize papillary, peripapillary, and macular microvasculature and identify important vascular biomarker of ischemia and, potentially, visual prognosis. SUMMARY: Multimodal ophthalmic imaging can help in the diagnosis of ODD and optic disc edema and identify patients at high risk of vision loss and neurological issues in order to ensure appropriate diagnosis and treatment.

Unilateral optic disc drusen mis-diagnosed as optic neuritis: Diagnostic and therapeutic implications.

Objective: To present a case of unilateral optic disc drusen, initially mis-diagnosed as optic neuritis, which led to chronic systemic administration of steroids and the development of hypercortisolism. Methods: A 22-year-old female was referred because of the lack of improvement of the manifestations of optic neuritis despite the chronic use of systemic steroids. Presence of unilateral optic disc edema was initially observed, associated with ipsilateral scotomata and increased ipsilateral latency time in visually evoked potentials (VEP). Results: A CT scan, A and B ultrasonography and autofluorescence of the optic disc confirmed the diagnosis of optic disc drusen. Conclusions: In cases of optic disc edema, the possibility of drusen should always be examined even if functional disturbances, such as scotomas in visual fields or electrophysiological findings, are present, to avoid potential toxicity from unnecessary medications.

The Pathophysiological Significance of Fibulin-3.

Fibulin-3 (also known as EGF-containing fibulin extracellular matrix protein 1 (EFEMP1)) is a secreted extracellular matrix glycoprotein, encoded by the EFEMP1 gene that belongs to the eight-membered fibulin protein family. It has emerged as a functionally unique member of this family, with a diverse array of pathophysiological associations predominantly centered on its role as a modulator of extracellular matrix (ECM) biology. Fibulin-3 is widely expressed in the human body, especially in elastic-fibre-rich tissues and ocular structures, and interacts with enzymatic ECM regulators, including tissue inhibitor of metalloproteinase-3 (TIMP-3). A point mutation in EFEMP1 causes an inherited early-onset form of macular degeneration called Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD). EFEMP1 genetic variants have also been associated in genome-wide association studies with numerous complex inherited phenotypes, both physiological (namely, developmental anthropometric traits) and pathological (many of which involve abnormalities of connective tissue function). Furthermore, EFEMP1 expression changes are implicated in the progression of numerous types of cancer, an area in which fibulin-3 has putative significance as a therapeutic target. Here we discuss the potential mechanistic roles of fibulin-3 in these pathologies and highlight how it may contribute to the development, structural integrity, and emergent functionality of the ECM and connective tissues across a range of anatomical locations. Its myriad of aetiological roles positions fibulin-3 as a molecule of interest across numerous research fields and may inform our future understanding and therapeutic approach to many human diseases in clinical settings.

Vision Loss in Optic Disc Drusen Correlates With Increased Macular Vessel Diameter and Flux and Reduced Peripapillary Vascular Density.

PURPOSE: To determine the key optical coherence tomography (OCT) and OCT angiography (OCTA) parameters that correlate with visual field loss in optic disc drusen (ODD). DESIGN: Retrospective cross-sectional study. METHODS: Single academic center. Seventeen patients with ODD (29 eyes) and 35 age-matched controls (53 eyes). Static perimetry, OCT, and OCTA imaging of optic disc and macula. Static perimetry, OCT, and OCTA measurements. RESULTS: We investigated the relationship between static perimetry and 14 OCT/OCTA measurements in patients with ODD vs age-matched controls and found 5 key measurements that most correlated with visual field loss included: peripapillary retinal nerve fiber layer (RNFL), macular ganglion cell complex (GCC), peripapillary vessel area density (VAD), macular vessel diameter (VD), and flux. Hierarchical clustering of these 5 measurements vs all clinical characteristics revealed 3 distinct clusters. ODD and control eyes with no visual field loss (mean deviation [MD] > -2.0 dB) had high RNFL and GCC, and low macular VD and flux. ODD eyes with mild visual field loss (MD -2.0 to -5.0 dB) had high RNFL, GCC, and increased macular VD and flux. ODD eyes with moderate/severe visual field loss (MD < -5.0 dB) had decreased RNFL, GCC, peripapillary VAD, and increased macular VD and flux. CONCLUSIONS: OCT and OCTA provided objective measurements that can help predict visual field loss in ODD. Our data suggest that increased macular flow may be an early biomarker of visual field loss in ODD, while decreased peripapillary vessel density and RNFL thickness are late biomarkers of visual field loss in ODD.

Young Adults With Anterior Ischemic Optic Neuropathy: A Multicenter Optic Disc Drusen Study.

PURPOSE: Optic disc drusen (ODD), present in 2% of the general population, have occasionally been reported in patients with nonarteritic anterior ischemic optic neuropathy (NA-AION). The purpose of this study was to examine the prevalence of ODD in young patients with NA-AION. DESIGN: Retrospective, cross-sectional multicenter study. METHODS: All patients with NA-AION 50 years old or younger, seen in neuro-ophthalmology clinics of the international ODDS (Optic Disc Drusen Studies) Consortium between April 1, 2017, and March 31, 2019, were identified. Patients were included if ODD were diagnosed by any method, or if ODD were excluded by enhanced-depth imaging optical coherence tomography (EDI-OCT) using ODDS Consortium guidelines. NA-AION eyes with ODD were termed "ODD-AION"; those without were termed "NODD-AION". RESULTS: A total of 65 patients (127 eyes) with NA-AION were included (mean 41 years old). Of the 74 eyes with NA-AION, 51% had ODD-AION, whereas 43% of fellow eyes without NA-AION had ODD (P = .36). No significant differences were found between ODD-AION and NODD-AION eyes in terms of Snellen best-corrected VA or perimetric mean deviation. According to EDI-OCT results, 28% of eyes with NODD-AION had peripapillary hyperreflective ovoid mass-like structures (PHOMS); 7% had hyperreflective lines, whereas 54% with ODD-AION had PHOMS; and 66% had hyperreflective lines (P = .006 and P < .001, respectively). CONCLUSIONS: Most of these young NA-AION patients had ODD. This indicates that ODD may be an independent risk factor for the development of NA-AION, at least in younger patients. This study suggests ODD-AION be recognized as a novel diagnosis.

Enhanced Depth Imaging Optical Coherence Tomography of Optic Nerve Head Drusen in Children.

BACKGROUND: To assess the utility of enhanced depth imaging optical coherence tomography (EDI-OCT), compared with other conventional imaging modalities, for detecting and characterizing optic nerve head drusen (ONHD) in children. METHODS: We report a retrospective cross-sectional case series of consecutive pediatric patients (age ≤16 years) with ONHD confirmed using B-scan ultrasonography. All eyes were evaluated using spectral-domain OCT of the optic nerve head in conventional (non-EDI) and EDI modes, fundus autofluorescence (FAF), and standard automated perimetry. Detection rates and the capacity to characterize ONHD were compared between EDI-OCT, non-EDI-OCT, and FAF. RESULTS: Twenty-eight eyes of 15 patients (mean age 11 years; 60% female) were identified with definite ONHD that were confirmed by B-scan ultrasound. Among the technologies, EDI-OCT, non-EDI-OCT, FAF, and automated perimetry had findings consistent with ONHD in 24, 21, 18, and 4 eyes, respectively. EDI-OCT had a significantly better detection capability (86% of eyes) compared with FAF (P = 0.04) but not with non-EDI-OCT (P = 0.15). Similar to results previously reported in adult patients, EDI-OCT detected ONHD at different levels of depth; most were located anterior to the lamina cribrosa. ONHD detected by EDI-OCT appeared as hypo-reflective ovoid regions bordered by hyper-reflective material or as isolated hyper-reflective bands without a hypo-reflective core. The mean greatest diameter of ONHD seen on EDI-OCT was 449.7 (SD ±114.1) µm. CONCLUSIONS: EDI-OCT detects ONHD in most eyes identified as having drusen on B-scan ultrasonography. This technique has the potential to be an effective alternative first-line diagnostic and monitoring tool for ONHD, particularly for detecting buried drusen in children.

OCT angiography in optic disc drusen: comparison with structural and functional parameters.

BACKGROUND: Optic disc drusen (ODD) can cause retinal nerve fibre layer (RNFL) defects with progressive visual field (VF) loss. Microvascular changes are discussed as a cause. We measured the vessel density (VD) of the optic disc in ODD using optical coherence tomography angiography and compared it with a normal population. Another intent was to determine the sensitivity and correlations in comparison with functional (VF) and structural parameters (RNFL, minimum rim width (MRW), ganglion cell complex (GCC)). METHODS: We analysed the VD of 25 patients with ODD and an age-matched control population including 25 healthy participants using AngioVue (Optovue, Fremont, CA, USA). We obtained data about RNFL, GCC, Bruch's membrane opening MRW (Spectralis HRA & OCT; Heidelberg Engineering, Germany) and VF (standard automated perimetry; SITA 24-2). Low image quality and pathologies interfering with the diagnostics were excluded. Parametric data were analysed using the t-test and non-parametric values using the Mann-Whitney U test. Linear regression analysis was used to determine correlations using the Bravais-Pearson test. RESULTS: The VD was significantly reduced in the ODD group especially the peripapillary capillary VD (n=45 vs 50 eyes; mean 43.15% vs 51.70%). Peripapillary RNFL thickness correlated with the VD significantly (r=0.902 (n=44), 0.901 (n=44), 0.866 (n=45)). The RNFL analysis showed a reduction in ODD, especially the superior hemisphere (mean 107 µm, 129 µm; 49 vs 50 eyes). The GCC was significantly lower in the ODD group (n=38 vs 40; mean 87 µm vs 98 µm). Positive correlation between the VD and the GCC was significant (n=37, r=0.532). There is a significant negative correlation (n=19; r=-0.726) between the VD and the pattern standard deviation (PSD). CONCLUSION: This study reveals significant peripapillary microvascular changes in patients with ODD correlating with the RNFL and GCC reduction. There is a negative correlation between the PSD and the VD.

Inter-Device Comparison of Blue-Light Autofluorescence in Optic Disc Drusen.

PURPOSE: Monochromatic blue-light fundus autofluorescence has proven to be particularly useful for the detection of optic disc drusen (ODD). The aim of this study was to investigate how accurately novel confocal scanners can detect ODD by means of color fundus and autofluorescence images. METHODS: Images were taken in 20 consecutive patients' eyes with funduscopically visible ODD using the TrueColor Eidon AF (60 × 55°) and the spectral domain Spectralis HRA+OCT (30 × 30°). The features of ODD, including localization, extent, and intensity patterns of autofluorescence were compared and correlated with retinal nerve fiber layer (RNFL) thickness in OCT and perimetry findings. RESULTS: Mean patient age was 46 ± 6 years (6 females, 4 males). The TrueColor Eidon AF enabled accurate localization and extent estimation of the drusen area. Drusen presented as a homogeneous signal. The predilection site of ODD, which was nasally pronounced in >80% of cases, was associated with thinning of the RNFL and corresponding visual field defects. CONCLUSION: The TrueColor Eidon AF allows reliable detection of superficial ODD in nondilated eyes. Extended observational studies are needed to determine the value of this noninvasive, nonmydriatic procedure in terms of follow-up and progression analyses of ODD.

Important functional distress in a teenager with optic nerve drusen.

We present a case of bilateral optic disc drusen and severe visual field loss in a female patient diagnosed at a very young age.

The optic nerve drusen and haemodynamics.

PURPOSE: The optic nerve drusen (DON) are precisely described in many papers. But fewer papers evaluate real haemodynamics parameters (HP) in DON. Clinically, it has been shown, that the development and progression of visual field changes in DON is closely related to the hemodynamics of the ocular vascular supply - the optic nerve. DON can visually overlap the excavation optic disc, making it difficult to evaluate scotomas of the visual field in glaucoma. METHODS: HP was prospectively evaluated in 54 patients with compensated intraocular pressure and DON. The drusen at the optic nerve head have been detected by fundus examination and B-scan ultrasonography (USG). DON were divided into 3 groups according to the size of the individual drusen or the drusen complex. I. Group: area size up to 1.9 mm. II. Group: area size: 1.9 - 3.9 mm. III. Group: area size: 4,0 mm. HP - maximum systolic velocity (MSV), minimal diastolic velocity (MDV) and resistance indices (IR) and index pulsatility (IP) - were recorded at the central retinal artery (CRA), at the central retinal vein (CRV), at ciliares posteriores arteries breves (CPAb) and at the ophthalmic artery (AO). The values were divided into 3 groups: 1 - Physiological: CRA: 8.7 ± 0.9 / 2.9 ± 0.6 cm/s or RI: 0.70 ± 0.05. 2 - Slightly impaired: CRA: 6.6 ± 0.8 / 2.0 ± 0.5 cm/s, or RI: 0.75 ± -0.04. 3 - Significantly impaired: CRA: 5.2 ± 1.2 / 1.9 ± 0.7 cm/sec or RI: 0.79 ± 0.03. RESULTS: There was no linear relationship between size of DON and HP. Slight worsening of HP at the CRA was in I. Group (28.6 %), II. Group (48.3 %) and III. Group (62.4 %). Significant worsening of HP at the CRA was I. group (28.6 %), II. Group (48.3 %) and in III. Group (62.4 %). HP of the CPA and of the OA were not significant due to the presence and size of drusen. The relationship between individual variables was evaluated using the Pearson correlation coefficient 0.213. I. Group P: 0.354, II. Group P: 0.073, III. Group P: 0.287. CONCLUSIONS: HP is more often impaired in „large“ DON (Group III), rarely in Group I, but this is not a rule. HP cannot be predicted according to the size of the druse formation at the optic nerve. It seems that the deterioration of HP depends not only on the DON size but also on the location (the distance from the lamella cribriformis) and also to the vascular system intrapapillary.

The Influence of Volume and Anatomic Location of Optic Disc Drusen on the Sensitivity of Autofluorescence.

BACKGROUND: Optic disc drusen (ODD) are acellular deposits in the optic nerve head. ODD can be diagnosed using different imaging modalities, including enhanced depth imaging optical coherence tomography (EDI-OCT) and autofluorescence (AF). It is unknown which factors determine the sensitivity of AF. The aim of this study was to investigate the effect of volume and anatomic location of ODD on the sensitivity of AF. METHODS: Cross-sectional study. RESULTS: A total of 38 patients (75 eyes) with ODD were included. In 12 of 75 eyes (16%) and in 11 of 38 patients (29%), EDI-OCT detected ODD that were not detected by AF. In 24 distinctly solitary ODD, both increase in ODD volume (P = 0.0388) and a more superficial ODD location (P < 0.0001) increased the possibility of AF detection of ODD, when performing a multivariate analysis. CONCLUSIONS: EDI-OCT is superior to AF in the diagnosis of ODD. Volume and anatomic location of ODD have a significant impact on the sensitivity of AF.

The Effect of a Decrease in Intraocular Pressure on Optic Nerve Function in Patients with Optic Nerve Drusen.

PURPOSE: The aim of the study was to compare optic nerve function in eyes with brinzolamide-reduced intraocular pressure (IOP) and the fellow eyes of patients with optic disk drusen (ODD). METHODS: The study comprised 34 patients with bilateral ODD but no signs of any other ocular disease. The eyes with more advanced optic neuropathy were selected for treatment with an IOP-lowering drug, carbonic anhydrase inhibitor (brinzolamide); the fellow eyes served as the control. Static perimetry, pattern electroretinography (PERG), pattern visual-evoked potentials (PVEP), and retinal nerve fiber layer (RNFL) thickness were analyzed. The observation period was 12 months. RESULTS: The eyes with brinzolamide-reduced IOP exhibited a statistically significant decrease in the mean defect index of static visual field (p = 0.03), an increase in PERG N95 amplitude (from 2.94 to 4.41 µV; p = 0.0047), and RNFL thickness stabilization. A statistically significant decrease in RNFL thickness (from 83.21 to 79.85 µm; p = 0.0017) was found in the control eyes. CONCLUSIONS: A decrease in IOP in eyes with ODD results in improvement of retinal ganglion cell function and delays the progression of optic neuropathy. PERG should be performed in patients with ODD as it is a sensitive test for monitoring optic neuropathy.

Doyne Honeycomb Retinal Dystrophy (Malattia Leventinese, Autosomal Dominant Drusen).

In these conditions, drusen are present in childhood, but patients are asymptomatic, with good vision, until their 40s or 50s. Drusen are seen at the macula, around the edge of the optic nerve and/or nasal to the disc, in a radiating pattern (in particular, temporal to macula, as in Figs. 18.1, 18.2, 18.3, 18.4 and 18.5). The periphery is usually spared. Drusen increase in size and number with age. Peripapillary drusen are a characteristic finding. Visual loss later in life is due to pigment hyperplasia, geographic atrophy, and choroidal neovascular membrane (Figs. 18.6 and 18.7). Variability in the clinical picture is common within families.