Drusen Area Research Articles

Drusen in adaptive optics and SD‐OCT

Abstract Purpose The study objective was to explore the microscopic structure of soft macular drusen and surrounding retinal areas using an adaptive optics (AO) camera and to compare the findings to those from standard clinical examinations. Methods 18 patients of age between 65 and 85 and presenting soft macular drusen were recruited after aninitial scanning laser ophthalmoscope (SLO) examination. We used an AO flood‐illumination system to acquire high‐resolution images of selected drusen areas. Every acquisition provided a series of 20 consecutive reflectance images, out of which 10 were numerically averaged to produce an enhanced final image. The resulting AO images were analyzed in comparison with conventional infrared and autofluorescence fundus images and spectral optical coherence tomography scans. Results The soft drusen were visible in AO images as generally round areas delimited by a peripheral low‐reflectance line. Hyper reflective spots of size comprised between 2 and 15 μm were observed in many drusen inner areas. These bright spots were sometimes isolated, sometimes grouped into tight aggregates of 2 to 40 components. Cone photoreceptors were visible in areas between drusen in most AO images. Conclusion The microscopic structures observed in the AO images of soft drusen presents analogies with their described anatomopathologic characteristics, which could not be identified using other in vivo imaging techniques. AO technology could help to refine the clinical classification of macular drusen and obtain deeper insight in their link with the development of different types of advanced AMD. Author Disclosure Information: N. Massamba, None; B. Lamory, Imagine Eyes, G. Soubrane, None.

Spectral domain optical coherence tomography for quantitative evaluation of drusen and associated structural changes in non-neovascular age-related macular degeneration

Background/aims:To demonstrate how spectral domain optical coherence tomography (SDOCT) can better evaluate drusen and associated anatomical changes in eyes with non-neovascular age-related macular degeneration (AMD) compared with time domain optical...

Inflammation, Complement Factor H, and Age-Related Macular Degeneration: The Multi-Ethnic Study of Atherosclerosis

To describe the relationship of systemic inflammatory disease, complement factor H (CFH) Y402H (1277T-->C) genotype status and age-related macular degeneration (AMD) prevalence in a multiethnic population of whites, blacks, Hispanics, and Chinese. Population-based, cross-sectional study. We included 5887 persons aged 45 to 84 years with gradable AMD. Digital fundus photographs were used to measure AMD. Two years earlier, biomarkers of inflammation were measured and history of inflammatory disease and use of antiinflammatory agents obtained. Prevalence of AMD. While controlling for age, gender, race/ethnicity, and study site, there were no associations between systemic inflammatory factors and AMD severity. Higher levels of high-sensitivity C-reactive protein (odds ratio [OR] per standard deviation [SD] increase in natural log [ln] units, 2.34; 95% confidence interval [CI], 1.33-4.13) and interleukin-6 (OR per SD in ln, 2.06; 95% CI, 1.21-3.49) were associated with geographic atrophy but not other AMD end points. History of periodontal disease (OR, 1.68; 95% CI, 1.14-2.47) was related to increased retinal pigment. A history of arthritis was associated with soft distinct drusen (OR, 1.24; 95% CI, 1.06-1.46). A history of oral steroid use was related to large drusen (OR, 2.13; 95% CI, 1.14-3.97) and soft distinct drusen (OR, 1.76; 95% CI, 1.00-3.10) and history of cyclooxygenase 2 inhibitor use were associated with large drusen (OR, 1.50; 95% CI, 1.10-2.04), soft indistinct drusen (OR, 1.84; 95% CI, 1.09-3.10), and large drusen area (OR, 1.66; 95% CI, 1.02-2.71). Whites, blacks, and Hispanics with CFH Y402H CC variant genotype had the highest frequency of early AMD compared with those with wild TT genotype. The frequency of CFH did explain some of the difference in AMD prevalence between Chinese and Hispanics compared with whites, but did not explain the difference in prevalence between whites and blacks. This study confirmed associations of the Y402H CFH gene variant with AMD in nonwhite populations, but neither explained the lack of association between inflammatory factors and AMD in the cohort nor the basis for the observed differences in AMD prevalence across ethnic groups.

Weekly Vaccination with Copaxone (Glatiramer Acetate) as a Potential Therapy for Dry Age-Related Macular Degeneration

Purpose: Drusen formation in age-related macular degeneration (AMD) shares some similarities with Alzheimer's disease (AD), which is associated with amyloid deposits. Aggregated beta-amyloid induces microglia to become cytotoxic and block neurogenesis. Recent evidence showed that T cell-based vaccination with Copaxone in AD mice model resulted in modulation of microglia into neuroprotective phenotype and as a result in reduction of cognitive decline, elimination of plaque formation, and induction of neuronal survival and neurogenesis. The aim was to investigate whether the effect of Copaxone on drusen in dry AMD is similar to that on deposits of other age-related chronic neurodegenerative diseases such as Alzheimer disease (AD). Materials and Methods: Patients over 50 years of age with intermediate dry AMD in both eyes were randomized to receive Copaxone or sham injections and were weekly treated by subcutaneous injections of Copaxone (dose of 20 mg) or sham injections for 12 weeks. At baseline, 6-week, and 12-week visits, visual acuity, contrast sensitivity, fundus examination and photography, fluorescein angiography, and ocular coherent tomography were performed. Main outcome measure was a change in total drusen area (TDA) measured by Image-Pro software and presented in arbitrary units (AU). Results: Eight studied eyes of four treated patients showed a decrease in TDA from 48130 to 16205 AU at 12 weeks as compared to baseline. In contrast, four control eyes (two patients) demonstrated almost no change in TDA (from 32294 to 32781 AU). Conclusion: These preliminary results show that Copaxone reduces drusen area.

Grading for progression of Age Related Macular Degeneration in the London AMD Study

Abstract Purpose: The aim of this study was to assess interobserver variability when grading progression of Age Related Macular Degeneration (AMD) using the International Classification (IC) system and to assess agreement with clinical decision. Methods: Fifty eyes with a minimum of 5 years disease duration documented by colour photographs were selected from the London AMD Study. Changes related to early and late AMD were graded in a random fashion while masked to the main purpose of the study (FS) and then independently by another grader (IL). Images in time‐sequence were independently analysed for clinical changes. Digitized time‐sequential fundus images were then aligned in uniform fashion, arranged into multi‐layered composites using Adobe Photoshop and clinical assessment made (TP, ACB). Results were compared and a consensus decision was made. Results: Inter‐observer agreement was 89.4% for predominant phenotype (κ=0.84), 89.36%‐91.49% for CNV (κ=0.79‐0.83), 87.23%‐89.36% for GA (κ=0.62‐0.74) and 55.32% for area covered by drusen (κ=0.31). In 4 cases the clinical and IC classifications differed: drusen area in 2 and two of end‐stage disease grading; resulting in 97.8% concordance in identification of change. At baseline,34 eyes had soft drusen, 15 had CNV and one had GA. Of the 34 with Drusen, 14 developed CNV and 9 GA by the end of the study. Disappearance of drusen without end‐stage disease was recorded in two eyes. Conclusions: Overall, changes observed clinically were reflected accurately by the IC grading in the majority of cases. This provides a quantitative basis for using this classification system in longitudinal studies. The accidental observation of regressing drusen without end‐stage disease merits further investigation.

Cone-Mediated Multifocal Electroretinogram in Age-Related Macular Degeneration

To evaluate the progression of change in the cone-driven multifocal electroretinogram (mfERG) responses in patients previously identified as having high-risk, soft drusen 63 mum or greater. Seventeen eyes of 14 patients were reevaluated after 28 to 41 months. Fundus changes were graded depending on drusen size and extent. Each of the 103 mfERG responses was analyzed and compared with age-matched normal controls and with the baseline measurement. Stable visual acuity was found in 12 of the 17 eyes. Drusen size or extent was increased, decreased, and unchanged in 6, 3, and 8 eyes, respectively. The mfERG responses demonstrated a significant progression in the response density loss and in N1 and P1 implicit time delay compared with the baseline evaluation regardless of drusen change. The extent of response deterioration occurred over the entire retinal area tested. Eyes having decreased drusen at follow-up were typically associated with higher response delays at baseline and follow-up than eyes with stable or increased drusen. Early age-related macular degeneration is associated with a progressive loss in the cone-driven mfERG response despite stable visual acuity. The response deterioration extended beyond the visible drusen area. Implicit times seem to be an important predictor of drusen regression.

The Age-Related Eye Disease Study Severity Scale for Age-Related Macular Degeneration

To develop a fundus photographic severity scale for age-related macular degeneration (AMD). In the Age-Related Eye Disease Study, stereoscopic color fundus photographs were taken at baseline, at the 2-year follow-up visit, and annually thereafter. Photographs were graded for drusen characteristics (size, type, area), pigmentary abnormalities (increased pigment, depigmentation, geographic atrophy), and presence of abnormalities characteristic of neovascular AMD (retinal pigment epithelial detachment, serous or hemorrhagic sensory retinal detachment, subretinal or sub-retinal pigment epithelial hemorrhage, subretinal fibrous tissue). Advanced AMD was defined as presence of 1 or more neovascular AMD abnormalities, photocoagulation for AMD, or geographic atrophy involving the center of the macula. We explored associations among right eyes of 3212 participants between severity of drusen characteristics and pigmentary abnormalities at baseline and development of advanced AMD within 5 years of follow-up. A 9-step severity scale that combines a 6-step drusen area scale with a 5-step pigmentary abnormality scale was developed, on which the 5-year risk of advanced AMD increased progressively from less than 1% in step 1 to about 50% in step 9. Among the 334 eyes that had at least a 3-step progression on the scale between the baseline and 5-year visits, almost half showed stepwise progression through intervening severity levels at intervening visits. Replicate gradings showed agreement within 1 step on the scale in 87% of eyes. The scale provides convenient risk categories and has acceptable reproducibility. Progression along it may prove to be useful as a surrogate for progression to advanced AMD.

Detection of Age-Related Macular Degeneration Using a NonmydriaticDigital Camera and a Standard Film Fundus Camera

To compare gradings of lesions associated with age-related macular degeneration (AMD) from digital and stereoscopic film images. Instrument validation study. Sixty-two subjects (124 eyes) with varying degrees of AMD, including no AMD. Images of the optic disc and macula were taken using a 45 degrees digital camera (6.3 megapixels) through dark-adapted pupils and pharmacologically dilated pupils. In addition, 30 degrees stereoscopic retinal film images were taken through pharmacologically dilated pupils of the same eyes. All images were graded for drusen size, type, and area; pigmentary abnormalities; geographic atrophy; and neovascular lesions using the modified Wisconsin Age-Related Maculopathy Grading System. Exact agreement and unweighted kappa scores were calculated for paired gradings resulting from digital and film images. Agreement between gradings obtained from stereoscopic slide transparencies and digital nonstereoscopic images. Exact agreement between gradings of digital and stereoscopic film images taken through pharmacologically dilated pupils was 91% (kappa = 0.85) for the categories of none, early AMD, and late AMD. Exact agreement for gradings of digital images taken through dark-adapted pupils compared with gradings of film images was 80% (kappa = 0.69). Exact agreement for gradings of digital images captured through dark-adapted and pharmacologically dilated pupils was 86% (kappa = 0.78). In addition, kappa scores for agreement between different approaches for individual lesions were moderate to almost perfect. Gradings resulting from high-resolution digital images, especially when the pupil is pharmacologically dilated, are comparable with those resulting from film-based images. We conclude that digital imaging of the retina is useful for epidemiological studies of AMD.

Comparison of color to fluorescein angiographic images from patients with early-adult onset grouped drusen suggests drusen substructure

Purpose Recent structural and histochemical data from our laboratory indicate that human drusen often possess distinct, structural core domains. A similar, corelike structure is frequently noted clinically in some drusen-related conditions. To assess the nature of the corelike structures observed clinically, we evaluated color photographs and fluorescein angiograms from patients with early-adult onset grouped drusen (EAOGD). Design Retrospective case series. Methods The areas of the six largest drusen and hyperfluorescent lesions for eight patients confirmed to have EAOGD were estimated by two masked examiners (RRG, JCF). Data were normalized using a logarithmic transformation and evaluated using a mixed model analysis to account for intragrader, interobserver and intrasubject effects. Results The average color to hyperfluorescence drusen area ratio was 2.29 (SE, 0.06). The area of drusen viewed in color photographs significantly exceeds that of the corresponding area of hyperfluorescence ( P < .0001). The average drusen area (geometric mean) was 0.014 mm 2 (SE, 0.001 mm 2) and the average hyperfluorescent lesion area was 0.006 mm 2 (SE, 0.0005 mm 2). The areas of the hyperfluorescent lesions do not vary among the capillary, venous, and washout angiographic phases. The lesions exceed choroidal intensity and demonstrate prominent, uniformly hyperintense fluorescence throughout all but the choroidal phases of the angiogram. Conclusions These data show that large visible drusen in EAOGD are concentric to regions of hyperfluorescence, suggesting that drusen may possess clinically detectable, substructural domains. Ongoing studies seek to determine whether clinical evidence of drusen substructure may exist in other drusen-associated disorders, such as in age-related macular degeneration.

Risk of age-related macular degeneration in eyes with macular drusen or hyperpigmentation: the Blue Mountains Eye Study cohort.

To quantify the 5-year risk of age-related macular degeneration (AMD) in eyes with different macular drusen characteristics (ie, size, type, location, and total area) or hyperpigmentation in a population-based cohort. The Blue Mountains Eye Study examined 3654 residents during 1992-1994; 2335 (75.1% of survivors) were reexamined during 1997-1999. Retinal photographs were graded using the Wisconsin Age-Related Maculopathy Grading System. Incident AMD lesions were defined by development of neovascular AMD or geographic atrophy in eyes without these lesions at baseline (eyes at risk). Age-adjusted relative risks (RRs) were determined. Generalized estimating equation models were used to estimate odds ratios, adjusting for the correlation between eyes and other AMD risk factors. Main Outcome Measure Incidence of AMD. Of the 4634 eyes at risk, 52 (1.1%) developed neovascular or atrophic AMD lesions over 5 years. In right eyes, presence vs absence of the following macular signs predicted AMD: drusen that were 125 micro m or larger (13.9 vs 0.6%; age-adjusted RR, 5.7; 95% confidence interval [CI], 3.6-9.0), indistinct soft or reticular drusen (23.2% vs 0.4%; RR, 9.9; 95% CI, 6.4-15.4), total drusen area of half the disc area or more (31.4% vs 0.6%; RR, 13.5; 95% CI, 8.0-22.8), and hyperpigmentation (14.4% vs 0.5%; RR, 8.0; 95% CI, 5.4-11.9). After adjusting for age, sex, and smoking status, eyes with these signs at baseline had a high likelihood of developing AMD. Eyes with Age-Related Eye Disease Study categories 3 and 4 were 5 times more likely to develop AMD compared with eyes in categories 1 and 2. This study quantifies the 5-year risk of AMD in eyes with macular drusen and hyperpigmentation.

Influence of arterial hypertension and diet-induced atherosclerosis on macular drusen.

To evaluate whether development of macular drusen is influenced by experimentally induced chronic arterial hypertension and atherosclerosis. The prospective experimental study included 93 eyes of 51 elderly rhesus monkeys. The total study group was divided into groups with experimental arterial hypertension ( n=22), diet-induced atherosclerosis ( n=10), or both arterial hypertension and atherosclerosis ( n=29) and a control group without arterial hypertension or atherosclerosis ( n=32). Using color wide-angle fundus photographs taken at the beginning and the end of the study, age-related macular degeneration was graded by counting the number and estimating the mean size of drusen in the macular region. In the monkeys with arterial hypertension, the count and area of the macular drusen and the change in number and size of macular drusen during the follow-up period were significantly ( P<0.05) higher than in the monkeys of the control group. Correspondingly, the count and size of macular drusen were significantly ( P<0.05) correlated with the duration of arterial hypertension. In contrast, monkeys with only atherosclerosis did not vary significantly ( P>0.10) from monkeys of the control group in number and size of drusen. The macular drusen parameters were statistically ( P>0.20) independent of the duration of atherosclerosis. Similarly, the atherosclerotic monkeys and the monkeys of the control group did not vary significantly ( P>0.30) in the change of the macular drusen parameters during the follow-up period. Development of macular drusen as part of age-related macular degeneration in rhesus monkeys may be associated with experimentally induced arterial hypertension. It does not seem to be influenced by diet-induced atherosclerosis.

The Alzheimer's A beta -peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older individuals worldwide. The disease is characterized by abnormal extracellular deposits, known as drusen, that accumulate along the basal surface of the retinal pigmented epithelium. Although drusen deposition is common in older individuals, large numbers of drusen and/or extensive areas of confluent drusen represent a significant risk factor for AMD. Widespread drusen deposition is associated with retinal pigmented epithelial cell dysfunction and degeneration of the photoreceptor cells of the neural retina. Recent studies have shown that drusen contain a variety of immunomodulatory molecules, suggesting that the process of drusen formation involves local inflammatory events, including activation of the complement cascade. Similar observations in Alzheimer's disease (AD) have lead to the hypothesis that chronic localized inflammation is an important element of AD pathogenesis, with significant neurodegenerative consequences. Accordingly, the amyloid beta (A beta) peptide, a major constituent of neuritic plaques in AD, has been implicated as a primary activator of complement in AD. Here we show that A beta is associated with a substructural vesicular component within drusen. A beta colocalizes with activated complement components in these "amyloid vesicles," thereby identifying them as potential primary sites of complement activation. Thus, A beta deposition could be an important component of the local inflammatory events that contribute to atrophy of the retinal pigmented epithelium, drusen biogenesis, and the pathogenesis of AMD.

Prophylactic laser treatment in early age related maculopathy reduced the incidence of exudative complications

AIMTo investigate the effect of prophylactic laser treatment on drusen area and incidence of exudative lesions in patients with soft drusen maculopathy.METHODSIn a prospective study, patients with early age related...

Alcohol consumption and the 5-year incidence of age-related maculopathy: The beaver dam eye study

Objective This study evaluated alcohol consumption as a risk factor for incidence of age-related maculopathy (ARM). Design Persons aged 43 to 86 years in 1988 in Beaver Dam, Wisconsin, were examined from 1988 through 1990 and 1993 through 1995, n = 3684. The presence and severity of ARM at both examinations were determined from gradings of stereoscopic fundus photographs using the Wisconsin Age-related Maculopathy Classification System. Alcohol consumption was determined by self-report. Results Men drinking at least 78 g/week of alcohol from beer had a higher 5-year age-adjusted incidence of early ARM (10.6%) than did men who did not drink beer (6.9%), but the test for trend was only borderline significant ( P = 0.08). However, incidence of soft indistinct drusen ( P = 0.01), increased drusen area ( P < 0.01), and confluent drusen ( P = 0.02) are all associated with beer drinking in men. Increased retinal pigment and retinal pigment epithelial depigmentation are not associated with beer drinking in men or women nor are any lesions associated with total alcohol consumption or consumption from liquor or wine in either men or women. Conclusions Except for an association of beer drinking with retinal drusen in men, consumption of alcoholic beverages is not likely to be an important risk factor for incidence of ARM.

Seven year follow-up of age-related maculopathy in an elderly British population.

Despite age-related macular degeneration (AMD) being the commonest cause of blindness amongst the elderly in Western society, the incidence of new lesions is poorly documented and the natural history of existing disease remains ill understood. To document in an elderly population the incidence of new AMD lesions and the progression of pre-existing AMD over time. Baseline ophthalmic examinations were performed on a geographically defined random population sample of elderly people in 1982-4, and retinal photographs taken. The present study re-examined and re-photographed survivors after approximately 7 years using the same fundus camera. Photographs were randomly encoded, and independently graded for AMD features by two masked observers using the Wisconsin AMD grading system. Disagreements were resolved by review to reach a consensus. Eighty-two of the 88 participating survivors had photographs of gradable quality on both occasions in at least one eye. Mean age at follow-up was 87 years (range 84-97 years) and 70.7% of subjects were female. Paired photographs were available on 158 eyes, and showed important differences in drusen type, drusen area and characteristics of the retinal pigment epithelium (RPE) between initial and subsequent examinations. The 7 year incidence (and regression) of lesions was: drusen 30.6% (20.0%), RPE degeneration 54.5% (8.8%), increased pigment 11.6% (64.7%), subretinal haemorrhage 1.3%, subretinal scar/fibrin 1.3% and geographic study 1.3%. These unique population-based results provide new insight into the natural history of AMD in an elderly population.

Colour contrast sensitivity in patients with soft drusen, an early stage of ARM.

The present institutional study was undertaken in order to determine whether testing of colour contrast sensitivity is valuable in detecting early functional changes in patients at initial stages of age-related maculopathy (ARM). The study included 27 patients with soft drusen as an early sign of ARM and 29 age-matched normals. The area occupied by drusen was determined using a computer program. Colour contrast sensitivity was measured with a computer graphics system. Visual acuity, central visual field (Humphrey Field Analyser) and colour vision (D-15 panel) were normal in both groups. Mean colour contrast sensitivity was significantly lower in patients with early ARM (for the protan axis: p = 0.00019, for the deutan axis: p = 0.000078 and for the tritan axis: p = 0.000096) than in the controls. Interindividual variations were large. There was a tendency towards a bimodal distribution for all three colour axes, most evident for the tritan axis. We found a correlation of the drusen area with the protan and deutan thresholds for the fundus colour photographs r = 0.5 (p < 0.01) and r = 0.4 (p < 0.05), respectively, and with the tritan threshold for the angiograms r = 0.5 (p < 0.05). The findings suggest that colour contrast sensitivity may offer an additional possibility of predicting exudative ARM. Whether the patients with the highest thresholds are those who will be the first to show progression with indications of exudative ARM is not yet known. The patient group will be followed up in order to elucidate this question.

Effects of argon (green) laser treatment of soft drusen in early age-related maculopathy: a 6 month prospective study.

To evaluate whether perifoveal laser photocoagulation of soft drusen reduces the total area occupied by drusen. In a prospective, randomised study, 20 patients (mean age 71.3 (SD 7.7) years) with early age-related maculopathy (ARM) in the form of soft drusen and pigmentary changes and with good visual acuity (0.94 (0.09)) were treated with argon green laser photocoagulation. Mild laser burns (200 microns) were placed within a temporal horseshoe-shaped area, extending from a distance of no less than 500 microns from the centre of the fovea to the vascular arcades. They were placed on the drusen and scattered over areas where no drusen were present. Fundus colour photography and fluorescein angiography were performed at study entry as well as after 3 and 6 months. Nineteen age-matched patients (68.5 (6.2) years) with soft drusen maculopathy (visual acuity 0.95 (0.10)) were followed as a control group. Using a computer system, the area occupied by drusen was determined as a portion of the total area of a circle with a radius corresponding to 1250 microns in the fundus for the angiograms and 2500 microns for the colour photographs, respectively. At study entry, the mean area occupied by drusen in the treatment group was not significantly (p > 0.5-0.7) different from that of the control group. The mean drusen area of the angiograms and fundus colour photographs in the treated group decreased significantly from 19.3% to 13.8% (p = 0.002) and from 7.84% to 5.02% (p = 0.005), respectively. In the untreated group, the mean area occupied by drusen increased significantly from 17.4% to 20.4% (p = 0.030) and from 8.33% to 9.23% (p = 0.002), respectively. No significant changes in visual acuity (p > 0.05-0.5) or in visual fields (p > 0.05-0.3) occurred in either of the two groups during 6 months. The study suggests that the area occupied by soft drusen in patients with early ARM decreases after perifoveal laser photocoagulation but increases in an untreated control group.

Quantitative image analysis of macular drusen from fundus photographs and scanning laser ophthalmoscope images.

Drusen are common features in the ageing macula and are associated with exudative age-related macular degeneration (ARMD). They appear as characteristic structures in indirect mode infrared scanning laser ophthalmoscope (SLO) images. Manual counting of drusen area in SLO images has shown no significant difference from that in standard fundus photographs in 6 eyes of 5 patients (p > 0.5). Computerised image processing techniques have been applied to digitised colour fundus photographs and indirect mode images to quantify the area of the macula affected by drusen in an automated fashion. Application of these methods may permit objective and repeatable assessment of the natural history of macular drusen. For a specificity of 90%, a sensitivity of 60% for colour fundus photographs and 35% for SLO images has been achieved, when compared with manual counting. The colour fundus photograph method also showed superior reproducibility compared with the SLO technique.

Visual field deficits in early age-related macular degeneration

Patients with early age-related macular degeneration (AMD) may retain good visual acuity but experience distortion and other qualitative visual changes. The purpose of the present study was to determine whether deficits of form recognition, as well as of light sensitivity, were related to retinal pigment epithelial (RPE) atrophy and/or drusen. We assessed form recognition deficits by the Amsler grid and by a perimetric test of tetter recognition and sensitivity deficits by the macular threshold test of the Humphrey Field Analyzer in 59 patients with AMD and visual acuities of 20/40 or better. The number of defects on each test was compared with the area of RPE atrophy and with toe area of drusen determined from fundus photographs. Multiple regression analyses based on ordinal data revealed that the number of visual field defects by each test was significantly correlated with the area of atrophy, but not with the area of drusen. There was also no significant tendency for a patient with a regional preponderance of drusen to have more impairment in the corresponding visual field. These results suggest that deficits of form recognition, as well as of sensitivity, in patients with early stages of AMD can be attributed to alteration of photoreceptor function associated with RPE atrophy, but not with drusen.

Automated extraction and quantification of macular drusen from fundal photographs

The objective quantification of drusen (and other macular lesions) should have applications epidemiologically, in the study of the natural history of drusen, and with such instruments as the scanning laser ophthalmoscope. The automated extraction of drusen from photographs is technically difficult because of uneven macular reflectance, and the confusing pattern of darker vessels. We have developed a method using an IBM personal computer, an image digitising board and specially written software. Once the image is digitised, no further input from the operator is necessary. We present the results of manual counting versus automated counting on a small series of patients with drusen. The automated technique is highly reproducible, and will calculate the retinal area occupied by drusen. The area and numbers of drusen can be compared over time, giving an index of progression. Hard drusen are fairly well detected, but the detection of soft drusen with their lower contrast remains a problem. The technique cannot distinguish between drusen and other pale lesions (e.g., atrophic retinal changes).