Risk factors for conversion to neovascular age-related macular degeneration based on longitudinal morphologic and visual acuity data.

PURPOSE: To use longitudinal quantitative morphologic and visual acuity (VA) data to investigate the risk of choroidal neovascularization (CNV) event occurrence in eyes with dry age-related macular degeneration (AMD). DESIGN: Prospective observational study. PARTICIPANTS: A total of 513 participants (844 eyes) followed longitudinally in one center enrolled in the Age-Related Eye Disease Study (AREDS) or the Prophylactic Treatment of AMD Study (PTAMD). METHODS: We assessed images of previously obtained fundus photographs for the presence of macular pigmentation, drusen area, and drusen distribution (number and size), and fellow eye CNV status at baseline. Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity at each visit and the age of each subject were obtained. We used a longitudinal logistic mixed-effects model with random intercepts fitted to event occurrences to assess risk on a per eye basis. MAIN OUTCOME MEASURES: Odds ratios for CNV event. RESULTS: Thirty-one subjects (6.0%) had events. Only VA changes over time and follow-up interval showed statistically significant effects. Several statistical models that included VA at the previous visit were used. In 2 models, 3 categories of VA were used: ≤ 75 letters, >75 and ≤ 85 letters, and >85 letters. Two categories were used for follow-up: ≤ 3 years versus >3 years or ≤ 1 year versus >1 year. In the first model with categorization at 3 years, a decrease in acuity from the >85 letter category to ≤ 75 letters increased the odds of CNV by 16.9 times (P = 0.022). In the model with categorization at 1 year, a decrease in acuity from the >85-letter category to ≤ 75 letters increased the odds of CNV by 21.4 times (P = 0.0175). Differences between the follow-up intervals were significant (P = 0.043) and indicated a more than 7-fold increase in the odds. Changes in morphologic features of the macula did not show significant effects. CONCLUSIONS: A decrease in VA to ≤ 75 ETDRS letters in an eye with an initial ETDRS baseline acuity of >85 letters increases the likelihood of CNV by approximately 20-fold. This likelihood also increases with aging.

Is drusen area really so important? An assessment of risk of conversion to neovascular AMD based on computerized measurements of drusen.

PURPOSE: To assess the relative risk of an eye's conversion to wet age-related macular degeneration (AMD) based primarily on drusen measurements obtained from analysis of digitized images. METHODS: Four hundred forty-four subjects (820 eyes) enrolled in the Age-Related Eye Disease Study (AREDS I) and 78 subjects (129 eyes) from the Prophylactic Treatment of AMD trial (PTAMD) were studied retrospectively. Drusen size, distribution, drusen area, and hyperpigmentation in two central macular regions on baseline fundus images were determined using an image analysis algorithm. The relative risk for choroidal neovascularization (CNV) based on drusen area, presence of one or five large drusen, hyperpigmentation, and fellow eye status was calculated. RESULTS: Odds ratios (ORs) for measured drusen area within the 1000- and 3000-µm regions were 1.644* (1.251-2.162) and 1.278 (0.927-1.762) for AREDS eyes and 0.832 (0.345-2.005) and 1.094 (0.524-2.283) for PTAMD eyes (*P < 0.05). In the 1000-µm region, respective ORs for the presence of a large druse, hyperpigmentation, and fellow eye affected were 2.60, 1.71, and 6.44* for AREDS eyes and 8.24, 1.37, and 17.56* for PTAMD eyes; for the 3000-µm region, ORs were 3.45*, 3.40*, and 4.59* for AREDS and nonsignificant, 6.58, and 11.62* for PTAMD eyes, respectively. CONCLUSIONS: Total drusen area, presence of large drusen, and the presence of hyperpigmentation were not consistent risk factors for an eye's development of CNV. Risk depended on study cohort as well as location. Having an affected fellow eye was the strongest and most consistent risk factor across all models. A larger drusen area does not necessarily increase an eye's risk of conversion to CNV.

Analysis of the relationship between drusen size and drusen area in eyes with age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To examine the relationship between drusen counts and drusen area in eyes with age-related macular degeneration, and to correlate drusen areas between fellow eyes. PATIENTS AND METHODS: Digital images from 378 patients (756 eyes) were analyzed using a validated drusen detection algorithm. Total drusen area and the number of drusen of various sizes (small: < 62 microns, intermediate: 63-124 microns, large: 125-249 microns, etc) were recorded for the central 1,000- and 3,000-micron diameter macular regions. Correlations were assessed using structural equation models. RESULTS: For the 1,000-micron region, the number of intermediate drusen was more highly correlated to total drusen area than the number of large drusen (R = 0.91 vs 0.82); this difference was statistically significant. The correlation coefficients for drusen area between fellow eyes was 0.73. CONCLUSION: The number of large drusen does not correlate better with total drusen area than drusen of other sizes. The number of large drusen is not necessarily a good surrogate for total drusen area.

Identification and assessment of Schlemm's canal by spectral-domain optical coherence tomography.

PURPOSE: Measurements of human Schlemm's canal (SC) have been limited to histologic sections. The purpose of this study was to demonstrate noninvasive measurements of aqueous outflow (AO) structures in the human eye, examining regional variation in cross-sectional SC areas (on/off collector channel [CC] ostia [SC/CC] and nasal/temporal) in the eyes of living humans. METHODS: SC was imaged by spectral-domain optical coherence tomography with a 200-nm bandwidth light source. Both eyes of 21 healthy subjects and one glaucomatous eye of three subjects were imaged nasally and temporally. Contrast and magnification were adjusted to maximize visualization. Cross-sectional SC on and off SC/CC was traced three times by two independent masked observers using ImageJ (ImageJ 1.40g, http://rsb.info.nih.gov/ij/ Wayne Rasband, developer, National Institutes of Health, Bethesda, MD). The mean SC area was recorded. A linear mixed-effects model was used to analyze eye, nasal/temporal laterality, and SC area on or off SC/CC. RESULTS: SC area was significantly larger on SC/CCs than off (12,890 vs. 7,391 micorm(2), P < 0.0001) and was significantly larger on the nasal side than on the temporal (10,983 vs. 8,308 micorm(2), P = 0.009). SC areas were significantly smaller in glaucoma patients than in normal subjects, whether pooled (P = 0.0073) or grouped by on (P = 0.0215) or off (P = 0.0114) SC/CC. CONCLUSIONS: Aqueous outflow structures, including SC and CCs, can be noninvasively assessed in the human eye. These measurements will be useful in physiological studies of AO and will be clinically useful in the determination of the impact of glaucoma therapies on IOP as well as presurgical planning.

Prophylactic treatment of age-related macular degeneration report number 2: 810-nanometer laser to eyes with drusen: bilaterally eligible patients.

BACKGROUND AND OBJECTIVE: To determine the prophylactic and therapeutic value of a single subthreshold 810-nanometer laser treatment in patients with high risk drusen as a manifestation of dry age-related macular degeneration in both eyes. PATIENTS AND METHODS: The Prophylactic Treatment of Age-related Macular Degeneration study enrolled 1,278 eyes of 639 participants who were 50 years or older with at least 5 drusen 63 microm or more in diameter in each eye. Treatment consisted of the placement of an annular grid of 48 extrafoveal, subthreshold 810-nm diode laser applications centered at but sparing the foveola in one eye of each participant, with the fellow eye serving as a control. Development of choroidal neovascularization and change in best-corrected visual acuity were compared between treated and untreated eyes. RESULTS: Subthreshold laser treatment did not decrease the incidence of choroidal neovascularization in treated versus untreated eyes. A modest visual acuity benefit in treated eyes was found at 24 months (1.5 letter difference; P = .04) and in the treated eyes of participants with a baseline visual acuity between 20/32 and 20/63 (4.0 letter difference; P = .0034). However, this treatment effect was not sustained at 3 years. CONCLUSION: A single subthreshold 810-nanometer laser treatment to eyes of participants with bilateral high risk drusen is not an effective prophylactic strategy against choroidal neovascularization.

Comparison of StratusOCT and Cirrus HD-OCT imaging in macular diseases.

BACKGROUND AND OBJECTIVE: The Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) device is a spectral-domain optical coherence tomography system that allows faster data acquisition than the previous generation StratusOCT (Carl Zeiss Meditec, Dublin, CA), which is a time-domain device. The authors compared images from both units to determine the clinical usefulness of spectral-domain optical coherence tomography technology in patients with macular diseases. PATIENTS AND METHODS: Six consecutive patients were imaged with both the Cirrus HD-OCT and the StratusOCT devices and the images were compared. RESULTS: Cirrus HD-OCT images were typically more useful than StratusOCT images for assessing fine architectural details in macular pathology. The Cirrus HD-OCT software also facilitated a better understanding of three-dimensional data volumes. CONCLUSIONS: Commercially available spectral-domain optical coherence tomography is a clinically useful tool for visualizing and understanding macular diseases and offers benefits not inherent in previous generation machines.

Ultrahigh-resolution spectral domain optical coherence tomography imaging of the lamina cribrosa.

Study of the structure of the lamina cribrosa is critical in glaucoma research. The purpose of this study is to determine the optimal spectral domain optical coherence tomography imaging protocol for the digital isolation and display of the lamina cribrosa. Three-dimensional datasets centered on the lamina cribrosa were obtained with 200 X 200 to 512 X 512 A-scan densities. The effect of scan density and c-mode slab thickness was subjectively compared. Increasing slab thickness reduced the sharpness of visible prelamina and lamina cribrosa structures. In retrolamina structures, thin slabs provided good visualization, but increased slab size increased the visibility of deeper structures. Scan times as short as 2.3 seconds (256 X 256 A-scans) degraded visualization of the shape of the optic nerve head. The optical scan protocol for lamina cribrosa imaging appears to be a 3 x 3 mm 200 X 200 A-scan volume with the lamina cribrosa positioned near direct current.