Longitudinal Study of Visual Function in Dry Age-Related Macular Degeneration at 12 Months.

PURPOSE: To report the 1-year progression of visual impairment on psychophysical tests of visual function in patients with early and intermediate age-related macular degeneration (AMD). DESIGN: Prospective, observational study. PARTICIPANTS: Patients with early and intermediate AMD were enrolled from the existing population at the Duke Eye Center, and healthy age-matched control participants were recruited from family members or friends of the AMD patients and from the Duke Optometry and Comprehensive Eye Clinics. METHODS: Patients and control participants recruited during the baseline study were assessed at both 6 and 12 months after the initial study visit. Measurements of visual function included best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), low-luminance deficit (LLD), microperimetry percent-reduced threshold (PRT), microperimetry average threshold (AT), and cone contrast tests (CCTs). MAIN OUTCOME MEASURES: Changes in BCVA, LLVA, LLD, microperimetry PRT, microperimetry AT, and CCT results from baseline to 6 months and to 12 months were assessed. RESULTS: Eighty-five patients completed the 12-month examination (19 control participants, 27 early AMD patients, and 39 intermediate AMD patients). Longitudinal analysis detected significant changes from baseline within each group in microperimetry PRT and AT and in the intermediate AMD group only for BCVA and CCT results (P < 0.05). CONCLUSIONS: Microperimetry and CCT are able to detect functional changes resulting from progression of dry AMD within a period as short as 12 months. These functional markers may be useful end points in future clinical trials that assess the effect of potential treatments for AMD.

Visual Function Metrics in Early and Intermediate Dry Age-related Macular Degeneration for Use as Clinical Trial Endpoints.

PURPOSE: To evaluate and quantify visual function metrics to be used as endpoints of age-related macular degeneration (AMD) stages and visual acuity (VA) loss in patients with early and intermediate AMD. DESIGN: Cross-sectional analysis of baseline data from a prospective study. METHODS: One hundred and one patients were enrolled at Duke Eye Center: 80 patients with early AMD (Age-Related Eye Disease Study [AREDS] stage 2 [n = 33] and intermediate stage 3 [n = 47]) and 21 age-matched, normal controls. A dilated retinal examination, macular pigment optical density measurements, and several functional assessments (best-corrected visual acuity, macular integrity assessment mesopic microperimety, dark adaptometry, low-luminance visual acuity [LLVA] [standard using a log 2.0 neutral density filter and computerized method], and cone contrast test [CCT]) were performed. Low-luminance deficit (LLD) was defined as the difference in numbers of letters read at standard vs low luminance. Group comparisons were performed to evaluate differences between the control and the early and intermediate AMD groups using 2-sided significance tests. RESULTS: Functional measures that significantly distinguished between normal and intermediate AMD were standard and computerized (0.5 cd/m2) LLVA, percent reduced threshold and average threshold on microperimetry, CCTs, and rod intercept on dark adaptation (P < .05). The intermediate group demonstrated deficits in microperimetry reduced threshhold, computerized LLD2, and dark adaptation (P < .05) relative to early AMD. CONCLUSIONS: Our study suggests that LLVA, microperimetry, CCT, and dark adaptation may serve as functional measures differentiating early-to-intermediate stages of dry AMD.

Intravitreal Anti-VEGF Injections Reduce Aqueous Outflow Facility in Patients With Neovascular Age-Related Macular Degeneration.

Purpose: We assess the effect of intravitreal anti-VEGF injections on tonographic outflow facility. Methods: Patients with age-related macular degeneration who had received unilateral intravitreal anti-VEGF injections were recruited into two groups, those with ≤10 and those with ≥20 total anti-VEGF injections. Intraocular pressure and tonographic outflow facility of injected and uninjected fellow eyes were measured and compared between groups. Risk factors for development of reduced outflow facility also were assessed. Results: Outflow facility was 12% lower in the injected eyes of patients who received ≥20 anti-VEGF injections, compared to contralateral uninjected eyes (P = 0.02). In contrast, there was no facility reduction for patients with ≤10 anti-VEGF injections (P = 0.4). In patients with ocular hypertension in the uninjected eye (IOP > 21 mm Hg, n = 5), the outflow facility of injected eyes was on average 46% lower (P = 0.01) than in the uninjected fellow eyes. This was significantly greater than the difference observed in patients with IOP ≤ 21 mm Hg in the uninjected eye (P = 2 × 10-4). In patients with ocular hypertension in the injected eye (n = 6) the differences in facility and IOP between contralateral eyes were significantly greater than in patients with IOP ≤ 21 mm Hg in the injected eye (P = 2 × 10-4 and P = 7 × 10-4, respectively). Conclusions: Chronic anti-VEGF injections significantly reduce outflow facility in patients with AMD. The greatest facility reduction is observed in patients with baseline ocular hypertension. Ophthalmologists who administer anti-VEGF injections should be aware of these findings and monitor patients closely for changes in IOP or evidence of glaucoma, especially in those with pre-existing ocular hypertension.

VISUAL FUNCTION MEASURES IN EARLY AND INTERMEDIATE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The objectives of this study were to evaluate 1) the feasibility of performing computerized tests of low luminance visual acuity (LLVA), cone-specific contrast (Cone Contrast Test [CCT]), contrast sensitivity, and microperimetry and 2) the test-retest repeatability of these outcomes in dry age-related macular degeneration (AMD). METHODS: This prospective study enrolled 30 subjects at a single site (8 controls, 8 early AMD, and 12 intermediate AMD). Subjects underwent LLVA, contrast sensitivity, CCT, and microperimetry with eye tracking. Low luminance deficit was defined as best-corrected visual acuity minus LLVA in EDTRS letters. Follow-up testing was administered at approximately 1 month. RESULTS: There was high test-retest repeatability at one month for all visual function metrics (intraclass correlations >0.7) except log contrast sensitivity (intraclass correlations 0.6). Compared with controls, patients with intermediate AMD showed significant deficits on best-corrected visual acuity, LLVA, low luminance deficit, percent-reduced threshold on microperimetry, and red CCT (P < 0.05), but not on contrast sensitivity, green and blue CCT. CONCLUSION: This pilot study supports the feasibility and reliability of using LLVA, microperimetry, and CCT in early dry AMD. Our data suggest these measures can be used as alternative future clinical trial endpoints. A larger, prospective natural history study of alternative visual function measures in dry AMD is warranted.

DYNAMIC CHANGES OF THE ANTERIOR CHAMBER ANGLE PRODUCED BY INTRAVITREAL ANTI-VASCULAR GROWTH FACTOR INJECTIONS.

PURPOSE: To use anterior segment optical coherence tomography (AS-OCT) to evaluate the anterior chamber after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. METHODS: Preinjection and immediate postinjection AS-OCT images were taken and measurements were compared including angle opening distance (AOD) and trabeculo-iris space area (TISA) at 500 µm and 750 µm from the scleral spur (AOD500, AOD750, TISA500 and TISA750, respectively), and the scleral spur angle. RESULTS: Twenty-one eyes from 21 patients were studied. There was significant narrowing of the temporal AOD500, AOD750, and temporal angle after injection (P = 0.03, 0.01, and 0.02, respectively). The percentage of narrowing of the nasal TISA500 and TISA750 was significantly greater in phakic versus pseudophakic eyes (P = 0.03 and 0.02, respectively). A higher postinjection IOP was correlated with increased narrowing of the nasal AOD500, TISA500, TISA750, and nasal angle (R = 0.22, 0.28, 0.34 and 0.20; P = 0.03, 0.01, 0.005 and 0.04, respectively) and a smaller preinjection anterior chamber depth in phakic eyes (R = 0.53, P = 0.01). CONCLUSION: After an anti-vascular endothelial growth factor injection, there is significant narrowing of the temporal anterior chamber angle in all eyes and increased narrowing of the nasal angle in phakic compared with pseudophakic eyes. Physicians performing intravitreal injections should be aware of these associations as they may contribute to our understanding of prolonged elevation of IOP after injections.

Wide field of view swept-source optical coherence tomography for peripheral retinal disease.

BACKGROUND/AIMS: To assess peripheral retinal lesions and the posterior pole in single widefield optical coherence tomography (OCT) volumes. METHODS: A wide field of view (FOV) swept-source OCT (WFOV SSOCT) system was developed using a commercial swept-source laser and a custom sample arm consisting of two indirect ophthalmic lenses. Twenty-seven subjects with peripheral lesions (choroidal melanomas, choroidal naevi, sclerochoroidal calcification, retinitis pigmentosa, diabetic retinopathy, retinoschisis and uveitis) were imaged with the WFOV SSOCT. Volumes were taken in primary gaze. Using the optic nerve to fovea distance as a reference measurement, comparisons were made between the lateral FOV of the WFOV SSOCT, current generation spectral-domain OCT (SDOCT) and widefield scanning laser ophthalmoscopy (SLO) of the same eyes. RESULTS: Peripheral pathologies were captured with WFOV SSOCT in 26 of the 27 subjects. The one not captured was in the far nasal periphery and was not seen in the primary gaze volume. Posterior pole associated pathologies were captured in all subjects. Current generation SDOCT had a mean lateral FOV of 2.08±0.21 optic nerve to fovea distance units, WFOV SSOCT had an FOV of 4.62±0.62 units and SLO had an FOV of 9.35±1.02 units. CONCLUSIONS: WFOV OCT can be used to examine both peripheral retinal pathology and the posterior pole within a single volume acquisition. SLO had the greatest FOV, but does not provide depth information. Future studies using widefield OCT systems will help further delineate the role of WFOV OCT to quantitatively assess and monitor peripheral retinal disease in three dimensions.

Spectral-domain optical coherence tomography characteristics of intermediate age-related macular degeneration.

PURPOSE: Describe qualitative spectral-domain optical coherence tomography (SD-OCT) characteristics of eyes classified as intermediate age-related macular degeneration (nonadvanced AMD) from Age-Related Eye Disease Study 2 (AREDS2) color fundus photography (CFP) grading. DESIGN: Prospective cross-sectional study. PARTICIPANTS: We included 345 AREDS2 participants from 4 study centers and 122 control participants who lack CFP features of intermediate AMD. METHODS: Both eyes were imaged with SD-OCT and CFP. The SD-OCT macular volume scans were graded for the presence of 5 retinal, 5 subretinal, and 4 drusen characteristics. In all, 314 AREDS2 participants with ≥1 category-3 AMD eye and all controls each had 1 eye entered into SD-OCT analysis, with 63 eyes regraded to test reproducibility. MAIN OUTCOME MEASURES: We assessed SD-OCT characteristics at baseline. RESULTS: In 98% of AMD eyes, SD-OCT grading of all characteristics was successful, detecting drusen in 99.7%, retinal pigment epithelium (RPE) atrophy/absence in 22.9%, subfoveal geographic atrophy in 2.5%, and fluid in or under the retina in 25.5%. Twenty-eight percent of AMD eyes had characteristics of possible advanced AMD on SD-OCT. Two percent of control eyes had drusen on SD-OCT. Vision loss was not correlated with foveal drusen alone, but with foveal drusen that were associated with other foveal pathology and with overlying focal hyperreflectivity. Focal hyperreflectivity over drusen, drusen cores, and hyper- or hyporeflectivity of drusen were also associated with RPE atrophy. CONCLUSIONS: Macular pathologies in AMD can be qualitatively and reproducibly evaluated with SD-OCT, identifying pathologic features that are associated with vision loss, RPE atrophy, and even possibly the presence of advanced AMD not apparent on CFP. Qualitative and detailed SD-OCT analysis can contribute to the anatomic characterization of AMD in clinical studies of vision loss and disease progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Spatial correlation between hyperpigmentary changes on color fundus photography and hyperreflective foci on SDOCT in intermediate AMD.

PURPOSE: Macular hyperpigmentation is associated with progression from intermediate to advanced age-related macular degeneration (AMD). The purpose of this study was to accurately correlate hyperpigmentary changes with spectral domain optical coherence tomography (SDOCT) hyperreflective foci in eyes with non-advanced AMD. METHODS: A prospective cross-sectional analysis of 314 eyes (314 subjects) with intermediate AMD was performed in the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SDOCT Study to correlate hyperpigmentary changes on color fundus photographs (CFP) with abnormal morphology on SDOCT. Spatial coregistration was performed with an automated algorithm in two nonoverlapping subsets of 20 study eyes, which permitted double-masked CFP and SDOCT grading by certified investigators. RESULTS: Macular CFP hyperpigmentation was significantly associated with SDOCT intraretinal hyperreflective foci in the 314 study eyes (P < 0.001). In a substudy of 40 eyes, automated intermodality spatial coregistration was successfully achieved in all 136 (100%) retinal regions selected for CFP and SDOCT grading. In one subset of 20 study eyes, 28 of 39 (71.8%) retinal CFP regions with hyperpigmentation were correlated with focal hyperreflectivity on SDOCT, versus seven of 39 (17.9%) control regions (P < 0.001). In another subset of 20 eyes, 21 of 29 (72.4%) SDOCT regions with hyperreflective foci were correlated with hyperpigmentary changes on CFP, versus two of 29 (6.9%) control regions (P < 0.001). CONCLUSIONS: A novel algorithm achieves automated intermodality spatial coregistration for masked grading of regions selected on CFP and SDOCT. In intermediate AMD, macular hyperpigmentation has high spatial correlation to SDOCT hyperreflective foci and often represents the same anatomical lesion. (ClinicalTrials.gov number, NCT00734487.).

Photoreceptor layer thinning over drusen in eyes with age-related macular degeneration imaged in vivo with spectral-domain optical coherence tomography.

PURPOSE: Detect changes in the neurosensory retina using spectral-domain optical coherence tomography (SD OCT) imaging over drusen in age-related macular degeneration (AMD). Quantitative imaging biomarkers may aid in defining risk of disease progression. DESIGN: Cross-sectional, case-control study evaluating SD OCT testing in AMD. PARTICIPANTS AND CONTROLS: Seventeen eyes of 12 subjects with nonneovascular AMD and drusen and 17 eyes of 10 age-matched control subjects. METHODS: Spectral-domain OCT imaging across the fovea in the study eye with multiple 10- to 12-mm scans of 1000 A scans each. MAIN OUTCOME MEASURES: In summed SD OCT scans, the height of individual retinal layers either over drusen or at corresponding locations in the control eye and qualitative changes in retinal layers over drusen. Secondary measures included photoreceptor layer (PRL) area, inner retinal area, and retinal pigment epithelium (RPE)/drusen area. RESULTS: The PRL was thinned over 97% of drusen, average PRL thickness was reduced by 27.5% over drusen compared with over a similar location in controls, and the finding of a difference was valid and significant (P=0.004). Photoreceptor outer segments were absent over at least 1 druse in 47% of eyes. Despite thinning of the PRL, inner retinal thickness remained unchanged. We observed 2 types of hyperreflective abnormalities in the neurosensory retina over drusen. Distinct hyperreflective speckled patterns occurred over drusen in 41% of AMD eyes and never in control eyes. A prominent hyperreflective haze was present in the photoreceptor nuclear layer over drusen in 67% of AMD eyes and more subtly in the photoreceptor nuclear layer in 18% of control eyes (no drusen). CONCLUSIONS: With SD OCT as used in this study, we can easily detect and measure changes in PRL over drusen. Decreased PRL thickness over drusen suggests a degenerative process, with cell loss leading to decreased visual function. The hyperreflective foci overlying drusen are likely to represent progression of disease RPE cell migration into the retina and possible photoreceptor degeneration or glial scar formation. A longitudinal study using SD OCT to examine and measure the neurosensory retina over drusen will resolve the timeline of degenerative changes relative to druse formation.

Wavelength independence and interdevice variability of optical coherence tomography.

BACKGROUND AND OBJECTIVE: Comparison of nerve fiber layer (NFL) thickness and macular retinal thickness measurements in two different commercial optical coherence tomography (OCT) machines with the same and different super luminescent diode lasers (SLDs). PATIENTS AND METHODS: Thirty eyes of 30 subjects were studied, with each eye scanned on two different OCT machines on the same day. Three 3.4-mm diameter circumpapillary NFL scans and six 6-mm radial scans centered on the fovea were obtained. Macular volumes were calculated from the central 3.45 mm of the 6 radial scans. RESULTS: The first study (identical SLDs of 850 nm) included 10 eyes of 10 subjects for mean NFL thickness and 6 eyes of 6 subjects for macular volume. There was no systematic difference between the measurements on the two machines for NFL (difference = 5.6 microm, standard error [SE] = 3.8, P= .18) or macular volume (difference = -0.003 mm3, SE = 0.064, P = .96). The second study (SLDs of 850 and 820 nm) included 20 eyes of 20 subjects. There was no significant difference between the two machines for mean NFL (difference = 3.4 microm, SE = 2.9, P= 0.26) or macular volume (difference = -.017 mm3, SE = 0.017, P= .33). For the smaller areas of the macular scan, several (including the outer ring) showed a significant systematic difference between measurements at the two wavelengths, but even these had at most 12% of the total variance attributable to the different wavelengths. CONCLUSION: Our study indicates that OCT measurements of NFL thickness do not differ much when the device or the wavelength of the SLD is changed. Some measurements of the macular thickness in specific areas may differ systematically for different wavelengths, but in most cases the difference is small.

Usage and cost of laser trabeculoplasty in the United States.

To determine annual usage and costs of laser trabeculoplasty (LTP) in the United States, we reviewed data from the Health Care Financing Administration from 1986 to 2000, using the Part B Extract and Summary System (BESS). The annual number of LTP procedures performed increased to a peak number of 176,670 in 1992 and has declined since that time, with a 57% reduction in the number of procedures performed in 2000 (75,838) compared with the peak number. The total allowed charges declined from a peak of $137,127,436 in 1991 to $27,622,073 in 2000 (80% reduction). The average allowed charge per procedure was highest in 1989 ($893), and by 2000 the average charge ($359) was reduced by 60% compared with the peak charge. The total number of LTP procedures performed in Medicare beneficiaries has decreased in recent years compared with the peak number in 1992. In recent years, there also has been a marked reduction in the total allowed charges and the average charge per procedure for LTP.