DIRECTIONAL OPTICAL COHERENCE TOMOGRAPHY IMAGING OF MACULAR PATHOLOGY.

PURPOSE: To survey the impact of directional reflectivity on structures within optical coherence tomography images in retinal pathology. METHODS: Sets of commercial optical coherence tomography images taken from multiple pupil positions were analyzed. These directional optical coherence tomography sets revealed directionally reflective structures within the retina. After ensuring sufficient image quality, resulting hybrid and composite images were characterized by assessing the Henle fiber layer, outer nuclear layer, ellipsoid zone, and interdigitation zone. Additionally, hybrid images were reviewed for novel directionally reflective pathological features. RESULTS: Cross-sectional directional optical coherence tomography image sets were obtained in 75 eyes of 58 patients having a broad range of retinal pathologies. All cases showed improved visualization of the outer nuclear layer/Henle fiber layer interface, and outer nuclear layer thinning was, therefore, more apparent in several cases. The ellipsoid zone and interdigitation zone also demonstrated attenuation where a geometric impact of underlying pathology affected their orientation. Misdirected photoreceptors were also noted as a consistent direction-dependent change in ellipsoid zone reflectivity between regions of normal and absent ellipsoid zone. CONCLUSION: Directional optical coherence tomography enhances the understanding of retinal anatomy and pathology. This optical contrast yields more accurate identification of retinal structures and possible imaging biomarkers for photoreceptor-related pathology.

FINGERPRINT SIGN OF THE HENLE FIBER LAYER.

PURPOSE: To describe the appearance of concentric, fingerprint-like waves within the Henle fiber layer (HFL) using en face optical coherence tomography in patients with tractional pathologies of the retina. METHODS: Retrospective analysis of six eyes of six patients imaged by optical coherence tomography with volumetric slabs positioned at the level of the HFL. RESULTS: Optical coherence tomography data from six patients with tractional vitreoretinal pathology were reviewed. Concentric, fingerprint-like microwaves were visualized through en face optical coherence tomography in all six study eyes at the level of the HFL. This finding resembled the finding of HFL waves previously noted histopathologically from force exerted on this layer. CONCLUSION: In retinal pathologies in which specific physical forces act on the retina, volumetric optical coherence tomography may permit visualization of en face concentric, fingerprint-like hyperreflective rings within the HFL. This "fingerprint sign" may represent a biomechanical consequence of traction on the retina and allow clinical decision making based on improved recognition of the existence of such traction.

EXPANDED CLINICAL SPECTRUM OF MULTIPLE EVANESCENT WHITE DOT SYNDROME WITH MULTIMODAL IMAGING.

PURPOSE: To evaluate and characterize multiple evanescent white dot syndrome abnormalities with modern multimodal imaging modalities. METHODS: This retrospective cohort study evaluated fundus photography, fluorescein angiography, indocyanine green angiography, optical coherence tomography, enhanced depth imaging optical coherence tomography, short-wavelength autofluorescence, and near-infrared autofluorescence. RESULTS: Thirty-four multiple evanescent white dot syndrome patients with mean age of 28.7 years were studied (range, 14-49 years). Twenty-six patients were women, and eight were men. Initial mean visual acuity was 0.41 logMAR. Final mean visual acuity was 0.03 logMAR. Fluorescein angiography shows a variable number of mid retinal early fluorescent dots distributed in a wreathlike pattern, which correlate to fundus photography, fundus autofluorescence, and indocyanine green angiography. Indocyanine green angiography imaging shows the dots and also hypofluorescent, deeper, and larger spots, which are occasionally confluent, demonstrating a large plaque of deep retinal hypofluorescence. Optical coherence tomography imaging shows multifocal debris centered at and around the ellipsoid layer, corresponding to the location of spots seen with photography, indocyanine green angiography, and fluorescein angiography. Protrusions of the hyperreflectant material from the ellipsoid layer toward the outer nuclear layer correspond to the location of dots seen with photography, indocyanine green angiography, and fluorescein angiography. CONCLUSION: Multimodal imaging analysis of the retina in patients with multiple evanescent white dot syndrome shows additional features that may help in the diagnosis of the disease and in further understanding its etiology. Multiple evanescent white dot syndrome is predominantly a disease of the outer retina, centered at the ellipsoid zone, but also involving the interdigitation zone and the outer nuclear layer.

Directional Optical Coherence Tomography Reveals Reliable Outer Nuclear Layer Measurements.

PURPOSE: Directional Optical Coherence Tomography (D-OCT) is a method used to optically segment and identify the outer nuclear layer (ONL) in vivo. The purpose of this study was to determine the repeatability and reproducibility of D-OCT ONL thickness measurements in healthy eyes. METHODS: Sixteen healthy eyes of sixteen subjects were imaged using the Cirrus SD-OCT. The OCT beam entry position was varied horizontally and vertically through the pupil, and cross-sectional images were obtained at baseline and 1-month follow-up by two observers. Detailed segmentation was performed to quantify the thickness of ONL without the inclusion of overlying Henle Fiber Layer. Inter-observer, intra-observer, and inter-visit variability was evaluated using Bland-Altman and coefficient of variation analysis for each category. RESULTS: All 16 eyes were successfully imaged, registered, and segmented. The maximum mean (SD) inter-operator difference was 2.6 (4.8) µm. The maximum mean (SD) intra-operator difference was 2.4 (5.3) µm. There was no statistically significant difference in ONL measurements detected between baseline and follow-up (p > 0.05). The mean (SD) differences measured across visits by one operator varied from -1.6 (3.1) to 1.1 (6.1) µm. The mean (SD) coefficient of variance (CV%) for all sectors with horizontal orientation was 9.1% (2.3%), 10.1% (2.5%), and 8.6% (2.3%) for inter-observer, intra-observer, and inter-visit, respectively. The mean (SD) coefficient of variance (CV%) for all sectors with vertical orientation was 8.3% (1.8%), 6.9% (1.4%), and 8.3% (2.1%) for inter-observer, intra-observer, and inter-visit, respectively. The majority of the variation of paired repeated measurements originated from between-subject variance. The within-subject variance accounted for less than 1% of the total variability. CONCLUSIONS: ONL thickness measurements can be quantified with good repeatability and reproducibility using D-OCT. Identifying the magnitude of D-OCT variability among normal subjects will allow for improved development of future clinical studies that quantitatively track the progression of macular pathology.

DIRECTIONAL OPTICAL COHERENCE TOMOGRAPHY PROVIDES ACCURATE OUTER NUCLEAR LAYER AND HENLE FIBER LAYER MEASUREMENTS.

PURPOSE: The outer nuclear layer (ONL) contains photoreceptor nuclei, and its thickness is an important biomarker for retinal degenerations. Accurate ONL thickness measurements are obscured in standard optical coherence tomography (OCT) images because of Henle fiber layer (HFL). Improved differentiation of the ONL and HFL boundary is made possible by using directional OCT, a method that purposefully varies the pupil entrance position of the OCT beam. METHODS: Fifty-seven normal eyes were imaged using multiple pupil entry positions with a commercial spectral domain OCT system. Cross-sectional image sets were registered to each other and segmented at the top of HFL, the border of HFL and the ONL and at the external limiting membrane. Thicknesses of the ONL and HFL were measured and analyzed. RESULTS: The true ONL and HFL thicknesses varied substantially by eccentricity and between individuals. The true macular ONL thickness comprised an average of 54.6% of measurements that also included HFL. The ONL and HFL thicknesses at specific retinal eccentricities were poorly correlated. CONCLUSION: Accurate ONL and HFL thickness measurements are made possible by the optical contrast of directional OCT. Distinguishing these individual layers can improve clinical trial endpoints and assessment of disease progression.

Sensitivity of fluid detection in patients with neovascular amd using spectral domain optical coherence tomography high-definition line scans.

PURPOSE: To determine the sensitivity of the Cirrus high-definition (HD) 5-line raster scans for detecting retinal fluid in neovascular age-related macular degeneration when using the spectral domain optical coherence tomography macular cubes as a gold standard. METHODS: Patients were retrospectively identified from their initial follow-up visit after being newly diagnosed with neovascular age-related macular degeneration in at least one eye. Patients were imaged with Cirrus spectral domain optical coherence tomography using the 512 × 128 macular cube scan and HD 5-line raster scan settings. Patients with other diseases that cause subretinal or intraretinal fluid, or who had an epiretinal membrane causing macular traction were excluded from the analysis. We recorded the presence or absence of subretinal or intraretinal fluid in the macular cube and on the HD 5-line raster scans. RESULTS: Seventy-nine patients met the study requirements. Of the 63 patients who had fluid present on the macular cube, 1 did not seem to have fluid on the HD 5-line raster scans. Taking the macular cube as a gold standard, the sensitivity of the HD 5-line raster scans for detecting retinal fluid in this cohort was 98.4%. CONCLUSION: The Cirrus HD 5-line raster scans have a high sensitivity for detecting fluid in the macular cube in patients with neovascular age-related macular degeneration.

En face spectral domain optical coherence tomography analysis of lamellar macular holes.

PURPOSE: To analyze the anatomical characteristics of lamellar macular holes using cross-sectional and en face spectral domain optical coherence tomography. METHODS: Forty-two lamellar macular holes were retrospectively identified for analysis. The location, cross-sectional length, and area of lamellar holes were measured using B-scans and en face imaging. The presence of photoreceptor inner segment/outer segment disruption and the presence or absence of epiretinal membrane formation were recorded. RESULTS: Forty-two lamellar macular holes were identified. Intraretinal splitting occurred within the outer plexiform layer in 97.6% of eyes. The area of intraretinal splitting in lamellar holes did not correlate with visual acuity. Eyes with inner segment/outer segment disruption had significantly worse mean logMAR visual acuity (0.363 ± 0.169; Snellen = 20/46) than in eyes without inner segment/outer segment disruption (0.203 ± 0.124; Snellen = 20/32) (analysis of variance, P = 0.004). Epiretinal membrane was present in 34 of 42 eyes (81.0%). CONCLUSION: En face imaging allowed for consistent detection and quantification of intraretinal splitting within the outer plexiform layer in patients with lamellar macular holes, supporting the notion that an area of anatomical weakness exists within Henle's fiber layer, presumably at the synaptic connection of these fibers within the outer plexiform layer. However, the en face area of intraretinal splitting did not correlate with visual acuity, disruption of the inner segment/outer segment junction was associated with significantly worse visual acuity in patients with lamellar macular holes.

Emerging concepts in the management of acute retinal necrosis.

Acute retinal necrosis (ARN), also known as Kirisawa-type uveitis, is an uncommon condition caused by infection of the retina by one of the herpes family of viruses, most typically varicella zoster virus or herpes simplex virus and less commonly cytomegalovirus. Clinical diagnosis can be challenging and is often aided by PCR-based analysis of ocular fluids. Treatment typically involves extended use of one or more antiviral agents. Long term retinal detachment risk is high. We review the literature on ARN and present an approach to the diagnosis and management of this serious condition.

Impact of Prophylactic Ranibizumab to Prevent Neovascular Age-Related Macular Degeneration on Eyes With Intermediate Age-Related Macular Degeneration.

Purpose: The purpose of this study was to determine the impact of prophylactic ranibizumab (PR) injections given every 3 months in eyes with intermediate nonexudative age-related macular degeneration (AMD) on drusen volume, macular layer thicknesses, and progression of geographic atrophy (GA) area over 24 months in the PREVENT trial. Methods: This post hoc analysis of the prospective PREVENT trial compared eyes with intermediate AMD randomized to PR versus sham injections to determine rates of conversion to neovascular AMD over 24 months. Drusen area and volume, macular thickness and volume, and retinal layer thicknesses were measured on spectral-domain optical coherence tomography images and analyzed. Masked grading of GA area and subretinal drusenoid deposits (SDDs) using fundus autofluorescence images was performed. Results: There were no statistical differences in drusen area and volumes between groups, and similar reductions in central subfield thickness, mean cube thickness, cube volume, and retinal sublayer thickness from baseline to 24 months (P = 0.018 to < 0.001), with no statistical differences between groups in any of these anatomic parameters. These findings were not impacted by the presence or absence of SDD. Among the 9 eyes with GA in this study, mean GA growth rate from baseline to 24 months was 1.34 +/- 0.79 mm2/year after PR and 1.95 +/- 1.73 mm2/year in sham-treated eyes (P = 0.49), and similarly showed no statistical difference with square root transformation (P = 0.61). Conclusions: Prophylactic ranibizumab given every 3 months did not appear to affect drusen volume, macular thinning, or GA progression in eyes with intermediate AMD. Translational Relevance: This work investigates the impact of PR on progressive retinal degeneration in a clinical trial.

Subclinical capillary changes in non-proliferative diabetic retinopathy.

PURPOSE: To establish adaptive optics scanning laser ophthalmoscopy as a method to detect and characterize microscopic signs of diabetic retinopathy in capillaries and cone photoreceptors in the parafovea. METHODS: Recently, adaptive optics scanning laser ophthalmoscope (AOSLO) has enabled noninvasive assessment of photoreceptors, capillaries, and leukocytes in the retinas of live human subjects. Repeated application of AOSLO imaging along with comparison to fluorescein angiography was used to track individual capillaries near the foveal avascular zone (FAZ) from one eye affected with severe non-proliferative diabetic retinopathy. Fluorescein angiography was used to identify clinical signs of diabetic retinopathy, such as microaneurysms and intraretinal microvascular abnormalities, and corresponding regions were imaged and assessed using the AOSLO. In addition, the structural integrity of photoreceptors and the spatial distribution of leukocytes around the parafoveal capillary network were quantitatively assessed. RESULTS: Capillaries and cone photoreceptors were visualized using the AOSLO without the use of injected contrast agents. Although the majority of capillaries were stable over a period of 16 months, one capillary at the edge of the FAZ dropped out, leading to a small but significant increase in FAZ size. Longitudinal assessment of the capillaries also showed microaneurysm formation and disappearance as well as the formation of tiny capillary bends similar in appearance to intraretinal microvascular abnormalities. The leukocytes in the capillary network were found to preferentially travel through the same routes in all four visits, suggesting that these channels are robust against small changes to the surrounding capillaries. In this eye, cone photoreceptor spacing was increased in the fovea when compared with normal data but stable across all visits. CONCLUSIONS: AOSLO imaging can be used to longitudinally track capillaries, leukocytes, and photoreceptors in diabetic retinopathy. Capillary changes that can be detected include dropout of individual capillaries as well as formation and disappearance of microaneurysms.

Central posterior hyaloidal fibrosis - A novel optical coherence tomography feature associated with choroidal neovascular membrane.

Purpose: To describe a novel optical coherence tomography (OCT) finding at the vitreomacular interface (VMI), and report its association with advanced choroidal neovascularisation (CNV). Observations: Optical coherence tomography (OCT) scans performed at three retinal imaging centres at Amanat Eye Hospital, Pakistan from May 2016 till May 2021 were reviewed. A specific change at the vitreomacular interface was noted consisting of abnormal hyper reflectivity at the point of attachment of the posterior hyaloid membrane to the foveal center which appears to 'fill in' the foveolar depression.Eight eyes of eight patients were identified. All affected eyes had advanced CNV and persistent vitreofoveolar adhesion. In all eyes, the foveal contour (concavity) was maintained and there was no inner retinal surface wrinkling which differentiates this OCT feature from vitreomacular traction or epiretinal membranes. The authors propose the term Central Posterior Hyaloidal Fibrosis (CPHF) for this specific OCT finding. Conclusions and Importance: Central Posterior Hyaloidal Fibrosis (CPHF) is a newly reported OCT finding associated with advanced CNV, which may represent a possible profibrotic influence of a choroidal neovascular membrane to the overlying posterior hyaloid adhesion.

Volumetric directional optical coherence tomography.

Photoreceptor loss and resultant thinning of the outer nuclear layer (ONL) is an important pathological feature of retinal degenerations and may serve as a useful imaging biomarker for age-related macular degeneration. However, the demarcation between the ONL and the adjacent Henle's fiber layer (HFL) is difficult to visualize with standard optical coherence tomography (OCT). A dedicated OCT system that can precisely control and continuously and synchronously update the imaging beam entry points during scanning has not been realized yet. In this paper, we introduce a novel imaging technology, Volumetric Directional OCT (VD-OCT), which can dynamically adjust the incident beam on the pupil without manual adjustment during a volumetric OCT scan. We also implement a customized spoke-circular scanning pattern to observe the appearance of HFL with sufficient optical contrast in continuous cross-sectional scans through the entire volume. The application of VD-OCT for retinal imaging to exploit directional reflectivity properties of tissue layers has the potential to allow for early identification of retinal diseases.

Multimodal imaging of soccer ball-related ocular posterior segment injuries.

PURPOSE: To investigate the clinical and anatomic characteristics of soccer ball-induced posterior segment injuries in the era of modern multi-modal imaging. METHODS: Retrospective case series of patients with soccer ball injury and diagnostic imaging from 2007 to 2020 at a single vitreoretinal practice. RESULTS: Eight patients met inclusion criteria. Fundus photographs (FP) and optical coherence tomography (OCT) were obtained in eight patients, fundus autofluorescence (FAF) in five patients, fluorescein angiography (FA) in three patients, and en-face OCT and OCT-Angiography (OCT-A) were obtained in two patients each. FA and FAF identified traumatic pigment epitheliopathy secondary to commotio. Increased hypo-autofluorescence was associated with shallow, peripheral retinal detachment on FAF. OCT of the macula displayed outer retinal changes associated with commotio, and offered insight into the acute and subacute changes of traumatic macular hole formation. A patient displayed foveal hyper-reflectivity in the shape of an hourglass with retinal cyst at the level of the external limiting membrane (ELM) as seen on OCT and En-face OCT. A patient with commotio involving the macula lacked microvascular changes on OCT-A. CONCLUSION: OCT, FA, and FAF imaging may aid in the work-up and management of the soccer ball-related posterior segment injuries.

Prophylactic Ranibizumab to Prevent Neovascular Age-Related Macular Degeneration in Vulnerable Fellow Eyes: A Randomized Clinical Trial.

PURPOSE: To determine whether prophylactic ranibizumab prevents the development of neovascular age-related macular degeneration (nAMD) in eyes with intermediate age-related macular degeneration (AMD) for patients with preexisting nAMD in their contralateral eye. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: Adults aged 50 years and older with intermediate AMD (multiple intermediate drusen [≥63 µm and <125 µm] or ≥1 large drusen [≥125 µm] and pigmentary changes) in the study eye and nAMD in the contralateral eye. INTERVENTION: Intravitreal ranibizumab injection (0.5 mg) or sham injection every 3 months for 24 months. MAIN OUTCOME MEASURES: Conversion to nAMD over 24 months (primary). Change in best-corrected visual acuity from baseline to 24 months (secondary). RESULTS: Among 108 enrolled participants (54 [50%] in each group), all except 2 were non-Hispanic Whites, 61 participants (56%) were female, and the mean age was 78 years. The mean baseline visual acuity was 77.7 letters (Snellen equivalent 20/32). Conversion to nAMD over 24 months occurred among 7 of 54 eyes (13%) in both groups (ranibizumab vs. sham hazard ratio = 0.91 [95% confidence interval (CI), 0.32-2.59]; P = 0.86). At 24 months, the cumulative incidence of nAMD adjusted for loss to follow-up was 14% (95% CI, 4%-23%) in the ranibizumab group and 15% (95% CI, 4%-25%) in the sham group. At 24 months, the mean change in visual acuity from baseline was -2.1 letters (standard deviation, 5.4 letters) with ranibizumab and -1.4 letters (standard deviation, 7.7 letters) with sham (adjusted difference = -0.8 letters [95% CI, -3.7 to 2.2 letters]; P = 0.62). The proportion of eyes that lost at least 10 letters of visual acuity from baseline at 24 months was 2 of 39 (5%) with ranibizumab and 4 of 40 (10%) with sham. There were no serious ocular adverse events in either group. CONCLUSIONS: Quarterly dosing of 0.5 mg ranibizumab in eyes with intermediate AMD did not reduce the incidence of nAMD compared with sham injections; however, the study was likely underpowered given the 95% CI, and a clinically meaningful effect cannot be excluded. There also was no effect on visual acuity at 24 months. Other strategies to reduce neovascular conversion in these vulnerable eyes are needed.

Three-Year Safety Results of SAR422459 (EIAV-ABCA4) Gene Therapy in Patients With ABCA4-Associated Stargardt Disease: An Open-Label Dose-Escalation Phase I/IIa Clinical Trial, Cohorts 1-5.

PURPOSE: To report on the safety of the first 5 cohorts of a gene therapy trial using recombinant equine infectious anemia virus expressing ABCA4 (EIAV-ABCA4) in adults with Stargardt dystrophy due to mutations in ABCA4. DESIGN: Nonrandomized multicenter phase I/IIa clinical trial. METHODS: Patients received a subretinal injection of EIAVABCA4 in the worse-seeing eye at 3 dose levels and were followed for 3 years after treatment. MAIN OUTCOME MEASURES: The primary end point was ocular and systemic adverse events. The secondary end points were best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, multifocal ERG, color fundus photography, short-wavelength fundus autofluorescence, and spectral domain optical coherence tomography. RESULTS: The subretinal injections were well tolerated by all 22 patients across 3 dose levels. There was 1 case of a treatment-related ophthalmic serious adverse event in the form of chronic ocular hypertension. The most common adverse events were associated with the surgical procedure. In 1 patient treated with the highest dose, there was a significant decline in the number of macular flecks as compared with the untreated eye. However, in 6 patients, hypoautofluorescent changes were worse in the treated eye than in the untreated eye. Of these, 1 patient had retinal pigment epithelium atrophy that was characteristic of tissue damage likely associated with bleb induction. No patients had any clinically significant changes in best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, or multifocal ERG attributable to the treatment. CONCLUSIONS: Subretinal treatment with EIAV-ABCA4 was well tolerated with only 1 case of ocular hypertension. No clinically significant changes in visual function tests were found to be attributable to the treatment. However, 27% of treated eyes showed exacerbation of retinal pigment epithelium atrophy on fundus autofluorescence. There was a significant reduction in macular flecks in 1 treated eye from the highest dose cohort. Additional follow-up and continued investigation in more patients will be required to fully characterize the safety and efficacy of EIAV-ABCA4.

Progression of geographic atrophy in age-related macular degeneration imaged with spectral domain optical coherence tomography.

PURPOSE: To determine the area and enlargement rate (ER) of geographic atrophy (GA) in patients with age-related macular degeneration (AMD) using the spectral domain optical coherence tomography (SD-OCT) fundus image. DESIGN: Prospective, longitudinal, natural history study. PARTICIPANTS: Eighty-six eyes of 64 patients with ≥6 months of follow-up. METHODS: Patients with GA secondary to AMD were enrolled in this study. Macular scans were performed using the Cirrus SD-OCT (Carl Zeiss Meditec, Dublin, CA). The areas of GA identified on the SD-OCT fundus images were quantified using a digitizing tablet. Reproducibility of these measurements was assessed and the ER of GA was calculated. The usefulness of performing square root transformations of the lesion area measurements was explored. MAIN OUTCOME MEASURES: Enlargement rate of GA. RESULTS: At baseline, 27% of eyes had a single area of GA. The mean total area at baseline was 4.59 mm(2) (1.8 disc areas [DA]). The mean follow-up time was 1.24 years. Reproducibility, as assessed with the intraclass correlation coefficient (ICC), was excellent on both the original area scale (ICC = 0.995) and the square root scale (ICC = 0.996). Intergrader differences were not an important source of variability in lesion size measurement (ICC = 0.999, 0.997). On average, the ER of GA per year was 1.2 mm(2) (0.47 DA; range, 0.01-3.62 mm(2)/year). The ER correlated with the initial area of GA (r = 0.45; P<0.001), but there were variable growth rates for any given baseline area. When the square root transformation of the lesion area measurements was used as a measure of lesion size, the ER (0.28 mm/yr) was not correlated with baseline size (r = -0.09; P = 0.40). In this cohort of lesions, no correlation was found between ER and length of follow-up. Square root transformation of the data helped to facilitate sample size estimates for controlled clinical trials involving GA. CONCLUSIONS: The SD-OCT fundus image can be used to visualize and quantify GA. Advantages of this approach include the convenience and assurance of using a single imaging technique that permits simultaneous visualization of GA along with the loss of photoreceptors and the retinal pigment epithelium that should correlate with the loss of visual function.

Spectral domain optical coherence tomography imaging of drusen in nonexudative age-related macular degeneration.

PURPOSE: To measure drusen area and volume in eyes with nonexudative age-related macular degeneration (AMD) using spectral domain optical coherence tomography imaging (SD-OCT). DESIGN: Evaluation of diagnostic technology. PARTICIPANTS: One hundred three eyes from 74 patients with drusen. METHODS: Patients with drusen secondary to nonexudative AMD were enrolled in this study. Five separate SD-OCT scans, each consisting of 40 000 uniformly spaced A-scans organized as 200 A-scans in each B-scan and 200 horizontal B-scans, were performed on each eye. Each scan covered a retinal area of 6×6 mm centered on the fovea. A novel algorithm was used to quantitatively assess drusen area and volume. Measurements from the entire scans, as well as in regions contained within 3- and 5-mm circles centered on the fovea, were analyzed. Test-retest standard deviations of drusen area and volume measurements were calculated for each eye. MAIN OUTCOME MEASURES: Drusen area and volume. RESULTS: The algorithm created drusen maps that permitted both qualitative and quantitative assessment of drusen area and volume. Both the qualitative appearance and the quantitative measurements of drusen area and volume were highly reproducible over the 5 different datasets. The intraclass correlation coefficient was >0.99 for both area and volume measurements on the entire dataset as well as the 3- and 5-mm circles. The correlation between lesion size and the test-retest standard deviations can be eliminated by performing a square root transformation of the area measurements and a cube root transformation of the volume measurements. These transformed data allowed for the inclusion of all drusen sizes in the calculation of an estimated single pooled test-retest standard deviation, which will be useful for longitudinal studies of drusen natural history. CONCLUSIONS: A novel algorithm for the qualitative and quantitative assessment of drusen imaged using SD-OCT was shown to be highly reproducible. The ability to assess drusen volume reliably represents a new quantitative parameter to measure in AMD and may be useful when assessing disease progression, particularly in trials for treatments of nonexudative AMD.