Susanna S. Park

Noninvasive Imaging of the Foveal Avascular Zone with High-Speed, Phase-Variance Optical Coherence Tomography

PURPOSEnTo demonstrate the application of phase-variance optical coherence tomography (pvOCT) for contrast agent-free in vivo imaging of volumetric retinal microcirculation in the human foveal region and for extraction of foveal avascular zone dimensions.nnnMETHODSnA custom-built, high-speed Fourier-domain OCT retinal imaging system was used to image retinas of two healthy subjects and eight diabetic patients. Through the acquisition of multiple B-scans for each scan location, phase differences between consecutive scans were extracted and used for phase-variance contrast, identifying motion signals from within blood vessels and capillaries. The en face projection view of the inner retinal layers segmented out from volumetric pvOCT data sets allowed visualization of a perfusion network with the foveal avascular zone (FAZ). In addition, the authors presented 2D retinal perfusion maps with pseudo color-coded depth positions of capillaries.nnnRESULTSnRetinal vascular imaging with pvOCT provides accurate measurements of the FAZ area and its morphology and a volumetric perfusion map of microcapillaries. In this study using two images from each fundus fluorescein angiography (FA) and pvOCT, the measured average areas of the FAZ from two healthy subjects were below 0.22 mm(2), and each of eight diabetic patients had an enlarged FAZ area, larger than 0.22 mm(2). Moreover, the FAZ areas demonstrated a significant correlation (r = 0.91) between measurements from FA and pvOCT.nnnCONCLUSIONSnThe high-speed pvOCT allows contrast agent-free visualization of capillary networks in the human foveal region that is analogous to fundus FA imaging. This could allow for noninvasive diagnosis and progression monitoring of diabetic retinopathy in clinical settings.

High resolution Fourier-domain optical coherence tomography of retinal angiomatous proliferation.

Purpose: To study the anatomic details of retinal angiomatous proliferation (RAP) in patients with age-related macular degeneration (AMD) using high-resolution Fourier-domain optical coherence tomography (Fd-OCT) and its three-dimensional reconstructions. Methods: A Fd-OCT instrument was used to image five patients clinically diagnosed with RAP. A series of 100 raster-scanned B-scans centered over the macula was registered and rendered as a three-dimensional volume. These retinal structures were analyzed for anatomic details of the RAP lesions. Results: The RAP lesion could be identified within the retina on Fd-OCT in all five cases. Fd-OCT images of the first four cases revealed areas of intraretinal neovascularization (IRN) in the deep retina adjacent to a pigment epithelial detachment (PED). There was neovascular proliferation anteriorly and posteriorly through a break in the retinal pigment epithelium (RPE). In three of the four cases, Bruch membrane remained intact. There was no identifiable choroidal neovascularization (CNV). The fifth case had both subretinal and sub-RPE neovascular membranes without a PED. Conclusion: Fd-OCT provides unprecedented in vivo detail of the anatomy of RAP lesions that nearly resembles histologic specimens. This study suggests that the initial neovascular process in RAP can originate either within the retina or in the sub-RPE space.

Effect of Diabetic Retinopathy and Panretinal Photocoagulation on Retinal Nerve Fiber Layer and Optic Nerve Appearance

OBJECTIVEnTo determine if panretinal photocoagulation (PRP) alters retinal nerve fiber layer (RNFL) thickness and optic nerve appearance.nnnMETHODSnPatients with diabetes who did and did not undergo PRP and nondiabetic control subjects were enrolled in a prospective study. Participants underwent optical coherence tomography of the peripapillary retina and optic nerve. Stereoscopic optic nerve photographs were graded in a masked fashion.nnnRESULTSnNinety-four eyes of 48 healthy individuals, 89 eyes of 55 diabetic patients who did not undergo PRP, and 37 eyes of 24 subjects with diabetes who underwent PRP were included in this study. Eyes that had been treated with PRP had thinner peripapillary RNFL compared with the other groups; this was statistically significantly different in the inferior (P = .004) and nasal (P = .003) regions. Optic nerve cupping did not increase with severity of disease classification, but the proportion of optic nerves graded as suspicious for glaucoma or as having nonglaucomatous optic neuropathy did (P = .008). These grading categories were associated with thinner RNFL measurements.nnnCONCLUSIONSnDiabetic eyes that have been treated with PRP have thinner RNFL than nondiabetic eyes. Optic nerves in eyes treated with PRP are more likely to be graded as abnormal, but their appearance is not necessarily glaucomatous and may be related to thinning of the RNFL.

Fourier-domain optical coherence tomography of eyes with idiopathic epiretinal membrane: correlation between macular morphology and visual function.

PurposeThe purpose of this study is to evaluate the macular morphological changes associated with idiopathic epiretinal membrane (iERM) using high-resolution Fourier-domain optical coherence tomography (FD-OCT), as they correlate with visual acuity and microperimetry (MP-1).MethodsIn all, 24 eyes (19 subjects) with iERM were imaged prospectively using FD-OCT with axial resolution of 4.5u2009μm and transverse resolution of 10 to 15u2009μm. MP-1 and Stratus OCT were carried out in a subset of eyes.ResultsThe mean log of the minimum angle of resolution best-corrected visual acuity (BCVA) was 0.18±0.16 (range: −0.08 to 0.48, Snellen equivalent 20/15−1 to 20/60). ERM was visualized in all 24 eyes with FD-OCT and in 17 eyes (85%) of 20 eyes imaged with Stratus OCT. Although BCVA correlated with macular thickening in the central 1u2009mm sub-field of the Stratus ETDRS (P=0.0005) and macular volume (central 3u2009mm area) on FD-OCT (P<0.0001), macular thickening on thickness map and volume correlated poorly with decrease in macular sensitivity on MP-1 (P=0.16). On FD-OCT, foveal morphological changes correlated best with decrease in BCVA, the strongest being central foveal thickness (P<0.0001). Other significant changes included blurring of the foveal inner segment–outer segment (IS–OS) junction and/or Verhoeffs membrane, vitreal displacement of foveal outer nuclear layer and foveal detachment (P<0.05). Foveal IS–OS junction disruption was seen in 25% of eyes on Stratus OCT but in none of the eyes on FD-OCT.ConclusionFD-OCT allowed improved visualization of ERM and associated foveal morphological changes that correlated best with BCVA. Macular thickening correlated weakly with decreased macular function as assessed by MP-1.

Comparison of retinal nerve fiber layer and central macular thickness measurements among five different optical coherence tomography instruments in patients with multiple sclerosis and optic neuritis.

Background: To compare the mean central macular thickness (CMT) and the mean average optic nerve retinal nerve fiber layer (RNFL) thickness in the eyes of patients with a history of optic neuritis and/or multiple sclerosis (MS) using 5 commercially available optical coherence tomography (OCT) instruments. Methods: Cross-sectional study including 46 patients (92 eyes) with a history of optic neuritis and/or MS. Both eyes were imaged on the same day with 5 OCT instruments: 1 time-domain OCT (Stratus) and 4 different Fourier-domain (spectral-domain) OCT (3D OCT-1000, Cirrus, RTVue-100, and Spectralis). Results: Twenty-five patients (50 eyes) were included in the final analysis after excluding patients with diabetes, glaucoma, ocular hypertension, or retinal pathology and inadequate scan quality. Randomized block analysis of variance revealed statistically significant differences across instruments (P < 0.001) for both eyes for mean CMT and mean average optic nerve RNFL. When testing for significant differences in measurements from instrument to instrument, some difference was noted between the right and left eyes. Conclusions: Statistically significant differences exist among commercially available OCT instruments in measuring mean CMT and mean average RNFL thickness in patients with optic neuritis and/or MS. These findings likely result from the differences in data acquisition and segmentation algorithm software among OCT instruments. Awareness of these variations among OCT instruments will be important in using these instruments for clinical trials and management of patients with optic neuritis and/or MS.

Reproducibility of macular thickness measurement among five OCT instruments: effects of image resolution, image registration, and eye tracking.

BACKGROUND AND OBJECTIVEnTo study the effect of image resolution, eye tracking, and image registration on central macular thickness reproducibility (rCMT) among spectral-domain and time-domain optical coherence tomography (SD-OCT and TD-OCT) instruments.nnnPATIENTS AND METHODSnSeventy-six eyes were imaged (44 normal, 32 maculopathy) either twice using four SD-OCT and one TD-OCT devices or three times using Spectralis SD-OCT (with and without eye tracking) (Heidelberg Engineering, Inc., Heidelberg, Germany). Cirrus images (Carl Zeiss Meditec, Dublin, CA) were further analyzed with three-point image registration.nnnRESULTSnAll instruments had superior rCMT in normal versus pathologic eyes (P < .001). No difference in rCMT was noted among instruments in normal eyes (P = .92), but TD-OCT was superior to SD-OCT (P = .017) in pathologic eyes. Cirrus image registration improved rCMT for normal eyes (P = .04), with borderline improvement in pathologic eyes (P = .06). Spectralis eye tracking improved rCMT in normal (P = .01) and pathologic (P = .004) eyes.nnnCONCLUSIONnHigher image resolution with SD-OCT may not improve rCMT, but image registration and eye tracking options may improve rCMT.

Ten-year follow-up of eyes treated with stereotactic fractionated external beam radiation for neovascular age-related macular degeneration

Purpose: To determine the long-term effects of stereotactic fractionated external beam radiation on eyes treated for neovascular age-related macular degeneration. Methods: A retrospective review of all eyes treated with stereotactic fractionated external beam radiation (20-40 Gy, 2-Gy fractions) between 1997 and 2000 was performed to identify eyes with ≥2-year follow-up for analysis. A subset was imaged prospectively using a high-resolution Fourier-domain optical coherence tomography. Results: Among 94 eyes treated, 33 eyes (32 subjects) had ≥2-year follow-up information (mean follow-up, 6.2 years; range, 2-10 years). Final visual acuity ranged from 20/50 to no light perception. Final macular findings included central geographic atrophy (49%), disciform scar (30%), and active choroidal neovascular membrane (9%). Fourier-domain optical coherence tomography images of three eyes with geographic atrophy revealed photoreceptor layer loss within areas of geographic atrophy with intact retinal morphology in areas of radiation exposure outside geographic atrophy. Radiation retinopathy was suspected in 18% and confirmed by fluorescein angiography in 15%, ranging from mild to neovascular glaucoma/phthisis bulbi (2 eyes). Mean time from stereotactic fractionated external beam radiation to development of radiation retinopathy was 5.4 years (range, 1-10 years). Conclusion: A moderate rate of delayed radiation retinopathy was noted in eyes with neovascular age-related macular degeneration treated with stereotactic fractionated external beam radiation. Geographic atrophy was a common finding.

Visual outcome correlates with inner macular volume in eyes with surgically closed macular hole.

Purpose: To determine the macular morphologic features that correlate best with visual outcome in eyes with surgically closed idiopathic macular hole. Methods: Transversal observational case series of 24 eyes (22 subjects) imaged postoperatively using high-resolution Fourier domain optical coherence tomography (FD-OCT). Total and inner macular volume for central 3 mm area, central foveal thickness, and size of foveal inner segment–outer segment junction abnormality were correlated with best-corrected visual acuity. Microperimetry (MP-1) test was performed in a subset of 18 eyes. Results: Mean postoperative best-corrected visual acuity was 20/36 (range, 20/25–20/70). Postoperative follow-up mean was 32.97 ± 24.68 months (range, 5–96 months). Eighteen eyes underwent internal limiting membrane (ILM) peeling. Among FD-OCT parameters, logarithm of the minimum angle of resolution best-corrected visual acuity and mean total microperimetry-1 sensitivity correlated best with inner macular volume in all eyes and ILM-peeled eyes (P < 0.05). Macular surface irregularities were noted in 12 eyes (66.7%) with ILM peeling but in none of the non–ILM-peeled eyes (P = 0.02). No significant correlation was found between microperimetry-1 sensitivity and other FD-OCT parameters. Conclusion: Because inner macular volume strongly correlated with visual outcome in eyes with surgically closed macular hole, the possible effect of ILM peeling on visual outcome needs to be further investigated.

Nonmydriatic Fundus Photography for Teleophthalmology Diabetic Retinopathy Screening in Rural and Urban Clinics

PURPOSEnTo evaluate the relative diagnostic value of nonmydriatic fundus photography (nFP) among patients screened for diabetic retinopathy in remote rural medical clinics and an urban academic medical center for nonadherence to recommended annual dilated eye examination.nnnSUBJECTS AND METHODSnA retrospective cross-sectional study was performed among diabetic patients seen in primary outpatient clinics between 2006 and 2011 who were screened for diabetic retinopathy with nFP for history of nonadherence to recommended annual dilated eye examination. A single nonstereoscopic, 45°, 10-megapixel digital image of the disc and macula of both eyes was obtained locally and transmitted electronically to a retinal specialist for remote review. The results from remote rural Native American Indian reservations were compared with those from an urban academic family practice clinic. The proportion of subjects diagnosed with diabetic retinopathy and the quality of fundus images were compared.nnnRESULTSnAmong 872 patients (1,744 eyes) screened from rural sites and 517 subjects (1,034 eyes) screened from an urban site, images were of good quality for evaluation in 82.4% and 85.7% of subjects, respectively. Diabetic retinopathy was noted in 12.6% of rural subjects and 29.6% of urban subjects (p<0.001).nnnCONCLUSIONSnnFP can be a useful tool in both rural and urban settings to screen for diabetic retinopathy in patients who are nonadherent to the recommended dilated annual eye exam. In our study population, a surprisingly higher percentage of diabetic subjects screened from the urban clinic had retinopathy compared with subjects screened in rural clinics.

Three-year follow-up of a pilot study of ranibizumab combined with proton beam irradiation as treatment for exudative age-related macular degeneration.

Background: To investigate the safety and tolerability of ranibizumab combined with proton beam irradiation in treating exudative age-related macular degeneration. Methods: Six eyes (6 subjects) with exudative age-related macular degeneration (4 newly diagnosed; 2 previous treated with ranibizumab) were treated with 4 monthly ranibizumab and 24 GyE proton beam irradiation (2 fractions, 24 hours apart) and seen monthly thereafter and retreated with ranibizumab for decrease in best-corrected visual acuity of ≥2 lines, new macular hemorrhage or fluid noted on optical coherence tomography. Results: Follow-up ranged from 12 months to 36 months (mean, 28 months). Baseline best-corrected visual acuity ranged from 20/40 to 20/250. Final best-corrected visual acuity ranged from 20/25 to 20/400. No radiation retinopathy was noted in any eye. Calculated radiation distribution dose curves indicate that ⩽10% of retina received ≥90% of radiation dose in all eyes. Two subjects lost ≥3 lines of best-corrected visual acuity during follow-up, 1 subject in both eyes from enlarging geographic atrophy and the other from worsening fibrovascular pigment epithelial detachment, which was refractory to multiple ranibizumab treatments before enrollment. Among 4 eyes with newly diagnosed exudative age-related macular degeneration, 3 had no fluid on optical coherence tomography at month 12 without further treatment. Conclusion: No safety concerns were noted after 3 years in eyes with exudative age-related macular degeneration treated with ranibizumab combined with proton beam irradiation in this small pilot study. A larger randomized prospective study is under way to further evaluate this combination therapy.