Laurel N. Vuong

Comparison of Spectral / Fourier Domain Optical Coherence Tomography Instruments for Assessment of Normal Macular Thickness

Purpose: The purpose of this study was to report normal macular thickness measurements and assess reproducibility of retinal thickness measurements acquired by a time-domain optical coherence tomography (OCT) (Stratus, Carl Zeiss Meditec, Inc., Dublin, CA) and three commercially available spectral/Fourier domain OCT instruments (Cirrus HD-OCT, Carl Zeiss Meditec, Inc.; RTVue-100, Optovue, Inc., Fremont, CA; 3D OCT-1000, Topcon, Inc., Paramus, NJ). Methods: Forty randomly selected eyes of 40 normal, healthy volunteers were imaged. Subjects were scanned twice during 1 visit and a subset of 25 was scanned again within 8 weeks. Retinal thickness measurements were automatically generated by OCT software and recorded after manual correction. Regression and Bland–Altman plots were used to compare agreement between instruments. Reproducibility was analyzed by using intraclass correlation coefficients, and incidence of artifacts was determined. Results: Macular thickness measurements were found to have high reproducibility across all instruments with intraclass correlation coefficients values ranging 84.8% to 94.9% for Stratus OCT, 92.6% to 97.3% for Cirrus Cube, 76.4% to 93.7% for RTVue MM5, 61.1% to 96.8% for MM6, 93.1% to 97.9% for 3D OCT-1000 radial, and 31.5% to 97.5% for 3D macular scans. Incidence of artifacts was higher in spectral/Fourier domain instruments, ranging from 28.75% to 53.16%, compared with 17.46% in Stratus OCT. No significant age or sex trends were found in the measurements. Conclusion: Commercial spectral/Fourier domain OCT instruments provide higher speed and axial resolution than the Stratus OCT, although they vary greatly in scanning protocols and are currently limited in their analysis functions. Further development of segmentation algorithms and quantitative features are needed to assist clinicians in objective use of these newer instruments to manage diseases.

Assessment of artifacts and reproducibility across spectral- and time-domain optical coherence tomography devices.

PURPOSE To report the frequency of optical coherence tomography (OCT) scan artifacts and to compare macular thickness measurements, interscan reproducibility, and interdevice agreeability across 3 spectral-domain (SD) OCT (also known as Fourier domain; Cirrus HD-OCT, RTVue-100, and Topcon 3D-OCT 1000) devices and 1 time-domain (TD) OCT (Stratus OCT) device. DESIGN Prospective, noncomparative, noninterventional case series. PARTICIPANTS Fifty-two patients seen at the New England Eye Center, Tufts Medical Center Retina Service, between February and August 2008. METHODS Two scans were performed for each of the SD OCT protocols: Cirrus macular cube 512 x 128 (software version 3.0; Carl Zeiss Meditec, Inc., Dublin, CA), RTVue (E)MM5 and MM6 (software version 3.5; Optovue, Inc., Fremont, CA), Topcon 3D Macular and Radial (software version 2.12; Topcon, Inc., Paramus, NJ), in addition to 1 TD OCT scan via Stratus macular thickness protocol (software version 4.0; Carl Zeiss Meditec, Inc.). Scans were inspected for 6 types of OCT scan artifacts and were analyzed. Interscan reproducibility and interdevice agreeability were assessed by intraclass correlation coefficients (ICCs) and Bland-Altman plots, respectively. MAIN OUTCOME MEASURES Optical coherence tomography image artifacts, macular thickness, reproducibility, and agreeability. RESULTS Time-domain OCT scans contained a significantly higher percentage of clinically significant improper central foveal thickness (IFT) after manual correction (11-mum change or more) compared with SD OCT scans. Cirrus HD-OCT had a significantly lower percentage of clinically significant IFT (11.1%) compared with the other SD OCT devices (Topcon 3D, 20.4%; Topcon Radial, 29.6%; RTVue (E)MM5, 42.6%; RTVue MM6, 24.1%; P = 0.001). All 3 SD OCT devices had central foveal subfield thicknesses that were significantly more than that of TD OCT after manual correction (P<0.0001). All 3 SD OCT devices demonstrated a high degree of reproducibility in the central foveal region (ICCs, 0.92-0.97). Bland-Altman plots showed low agreeability between TD and SD OCT scans. CONCLUSIONS Out of all OCT devices analyzed, cirrus HD-OCT scans exhibited the lowest occurrence of any artifacts (68.5%), IFT (40.7%), and clinically significant IFT (11.1%), whereas Stratus OCT scans exhibited the highest occurrence of clinically significant IFT. Further work on improving segmentation algorithm to decrease artifacts is warranted.

Subretinal Fluid From Anterior Ischemic Optic Neuropathy Demonstrated by Optical Coherence Tomography

OBJECTIVE To demonstrate the development of subfoveal fluid associated with optic disc swelling from nonarteritic anterior ischemic optic neuropathy. METHODS Optical coherence tomographic studies obtained during a 3-year period (October 1, 2003, to December 30, 2006) from 76 patients who developed ischemic optic neuropathy from 2 institutions were evaluated. The presence or absence, and the distribution, of subretinal fluid was determined. RESULTS Seventy-six patients underwent macular optical coherence tomography within 4 weeks of developing sudden loss of vision in one eye, decreased visual acuity, a visual field defect, a relative afferent pupillary defect, and optic disc swelling with peripapillary hemorrhages. Eight patients had apparent subretinal fluid extending into the subfoveal space. Visual acuity improved in 5 of the 8 patients as the subfoveal fluid resolved. CONCLUSIONS Subretinal fluid develops in some patients with nonarteritic anterior ischemic optic neuropathy and may contribute to some of the visual loss associated with this condition. Furthermore, resolution of the subretinal fluid could account for some of the visual improvement that can follow anterior ischemic optic neuropathy.

Projection OCT fundus imaging for visualising outer retinal pathology in non-exudative age-related macular degeneration

Aims: To demonstrate ultrahigh-resolution, three-dimensional optical coherence tomography (3D-OCT) and projection OCT fundus imaging for enhanced visualisation of outer retinal pathology in non-exudative age-related macular degeneration (AMD). Methods: A high-speed, 3.5 μm resolution OCT prototype instrument was developed for the ophthalmic clinic. Eighty-three patients with non-exudative AMD were imaged. Projection OCT fundus images were generated from 3D-OCT data by selectively summing different retinal depth levels. Results were compared with standard ophthalmic examination, including fundus photography and fluorescein angiography, when indicated. Results: Projection OCT fundus imaging enhanced the visualisation of outer retinal pathology in non-exudative AMD. Different types of drusen exhibited distinct features in projection OCT images. Photoreceptor disruption was indicated by loss of the photoreceptor inner/outer segment (IS/OS) boundary and external limiting membrane (ELM). RPE atrophy can be assessed using choroid-level projection OCT images. Conclusions: Projection OCT fundus imaging facilities rapid interpretation of large 3D-OCT data sets. Projection OCT enhances contrast and visualises outer retinal pathology not visible with standard fundus imaging or OCT fundus imaging. Projection OCT fundus images enable registration with standard ophthalmic diagnostics and cross-sectional OCT images. Outer retinal alterations can be assessed and drusen morphology, photoreceptor impairment and pigmentary abnormalities identified.

Three-dimensional ultrahigh resolution optical coherence tomography imaging of age-related macular degeneration

Ultrahigh resolution optical coherence tomography (OCT) enhances the ability to visualize different intra retinal layers. In age-related macular degeneration (AMD), pathological changes in individual retinal layers, including photoreceptor inner and outer segments and retinal pigment epithelium, can be detected. OCT using spectral / Fourier domain detection enables high speed, volumetric imaging of the macula, which provides comprehensive three-dimensional tomographic and morphologic information. We present a case series of AMD patients, from mild drusen to more advanced geographic atrophy and exudative AMD. Patients were imaged with a research prototype, ultrahigh resolution spectral / Fourier domain OCT instrument with 3.5 microm axial image resolution operating at 25,000 axial scans per second. These cases provide representative volumetric datasets of well-documented AMD pathologies which could be used for the development of visualization and imaging processing methods and algorithms.

High-speed ultrahigh resolution optical coherence tomography before and after ranibizumab for age-related macular degeneration.

OBJECTIVE To evaluate intraretinal anatomy in patients with exudative age-related macular degeneration (AMD) using high-speed ultrahigh resolution optical coherence tomography (hsUHR-OCT) before and 1 month after intravitreal injection of ranibizumab. DESIGN Retrospective case series. PARTICIPANTS Twelve eyes of 12 patients. METHODS A broad bandwidth superluminescent diode laser light source and spectral/Fourier domain signal detection were used to create a prototype hsUHR-OCT instrument with 3.5 mum axial image resolution and approximately 25,000 lines/second acquisition speed. Twelve eyes of 12 patients with exudative AMD were imaged with hsUHR-OCT before and 1 month after intravitreal ranibizumab injection. High pixel density and raster-scanned 3-dimensional (3D) OCT data sets were generated. Three-dimensional imaging software was used to calculate subretinal/retinal pigment epithelium fluid volume and volume of the fibrovascular lesion. MAIN OUTCOME MEASURES Qualitative and quantitative analysis of hsUHR-OCT images and 3D data sets. RESULTS All eyes had some degree of normalization of macular contour after intravitreal ranibizumab. The inner/outer photoreceptor segment junction visualized on hsUHR-OCT was discontinuous, overlying the fibrovascular lesion in all 12 of 12 eyes both before and after treatment; 9 of 12 eyes had focal areas of thinning of the outer nuclear layer, which remained after treatment. Volumetric measurements were possible in 8 of 12 eyes with 3D-rendering software. Fibrovascular lesion volume did not change significantly after treatment. CONCLUSIONS hsUHR-OCT is capable of unprecedented imaging speed and resolution, making it a valuable instrument in measuring in vivo intraretinal pathology. All 12 eyes had some normalization of macular contour. Fibrovascular lesion volume did not change significantly 1 month after treatment, suggesting that ranibizumab does not cause much initial regression of preexisting neovascular tissue. Photoreceptor abnormalities remained in all patients after treatment of wet AMD, suggesting that although ranibizumab improves overall retinal architecture, some photoreceptor damage may be irreversible. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Nitric oxide-induced homologous recombination in Escherichia coli is promoted by DNA glycosylases

Nitric oxide (NO*) is involved in neurotransmission, inflammation, and many other biological processes. Exposure of cells to NO* leads to DNA damage, including formation of deaminated and oxidized bases. Apurinic/apyrimidinic (AP) endonuclease-deficient cells are sensitive to NO* toxicity, which indicates that base excision repair (BER) intermediates are being generated. Here, we show that AP endonuclease-deficient cells can be protected from NO* toxicity by inactivation of the uracil (Ung) or formamidopyrimidine (Fpg) DNA glycosylases but not by inactivation of a 3-methyladenine (AlkA) DNA glycosylase. These results suggest that Ung and Fpg remove nontoxic NO*-induced base damage to create BER intermediates that are toxic if they are not processed by AP endonucleases. Our next goal was to learn how Ung and Fpg affect susceptibility to homologous recombination. The RecBCD complex is critical for repair of double-strand breaks via homologous recombination. When both Ung and Fpg were inactivated in recBCD cells, survival was significantly enhanced. We infer that both Ung and Fpg create substrates for recombinational repair, which is consistent with the observation that disrupting ung and fpg suppressed NO*-induced recombination. Taken together, a picture emerges in which the action of DNA glycosylases on NO*-induced base damage results in the accumulation of BER intermediates, which in turn can induce homologous recombination. These studies shed light on the underlying mechanism of NO*-induced homologous recombination.

Multifocal visual-evoked potential in unilateral compressive optic neuropathy

Aim: To evaluate the effects of unilateral compressive optic neuropathy on amplitude and latency of multifocal visual evoked potentials (mfVEPs). Methods: Static automated perimetry and mfVEP recordings were obtained from six patients with presumed meningiomas affecting one optic nerve. Monocular and interocular amplitude and latency analyses were performed and compared with normal control subjects. Results: The change in the mfVEP amplitude agreed with visual field findings with regard to topography and severity of deviation from normal. The delay in recordable responses from affected eyes ranged from 7.6 to 20.7 ms (interocular analysis) and 7.9 to 13.9 ms (monocular analysis). Conclusions: Compressive optic neuropathy decreases the amplitude and increases the latency of the mfVEP. The changes in latency were similar to those seen in optic neuritis but larger than those in ischaemic optic neuropathy and glaucoma.

Optical Coherence Tomography Angiography in Nonarteritic Anterior Ischemic Optic Neuropathy.

Background: Optical coherence tomography angiography (OCTA) has demonstrated good utility in qualitative analysis of retinal and choroidal vasculature and therefore may be relevant in the diagnostic and treatment efforts surrounding nonarteritic anterior ischemic optic neuropathy (NAION). Methods: Retrospective, cross-sectional study of 10 eyes of 9 patients with a previous or new diagnosis of NAION that received imaging with OCTA between November 2015 and February 2016. Two independent readers qualitatively analyzed the retinal peripapillary capillaries (RPC) and peripapillary choriocapillaris (PCC) for flow impairment. Findings were compared with automated visual field and structural optical coherence tomography (OCT) studies. Results: Flow impairment seen on OCTA in the RPC corresponded to structural OCT deficits of the retinal nerve fiber layer (RNFL) and ganglion cell layer complex (GCC) in 80% and 100% of eyes, respectively, and to automated visual field deficits in 90% of eyes. Flow impairment seen on OCTA in the PCC corresponded to structural OCT deficits of the RNFL and GCC in 70% and 80% of eyes, respectively, and to visual field deficits in 60%–80% of eyes. Conclusions: OCTA can noninvasively visualize microvascular flow impairment in patients with NAION.

Ganglion Cell Complex Loss in Chiasmal Compression by Brain Tumors

Background: Patterns of ganglion cell complex (GCC) loss detected by optical coherence tomography provide an objective measure of optic nerve injury. These patterns aid in early diagnosis and localization of chiasmal lesions. Methods: Twenty-three patients with chiasmal compression seen between 2010 and 2015 were imaged with the Cirrus high-definition optical coherence tomography macular cube 512 × 128, retinal nerve fiber layer (RNFL) scan protocols and automated (30-2 Humphrey) visual fields (VFs). Age-matched controls were included for comparison. Generalized estimating equations were performed comparing RNFL and GCC thicknesses between patients and their controls. Effect size (d) was calculated to assess the magnitude of difference between patients and controls. The average GCC and RNFL thicknesses also were correlated with VF mean deviation (MD). Pre operative average GCC thickness was correlated to post operative VF MD. Results: Patterns of GCC thinning corresponded to VF defects. The average GCC thickness was 67 ± 9 &mgr;m in patients and 86 ± 5 &mgr;m in controls (P < 0.001). The effect size was the greatest for GCC thickness (d = 2.72). The mean deviation was better correlated with GCC thickness (r2 =0.25) than RNFL thicknesses (r2 =0.15). Postoperatively, VF MD improved in 7 of 8 patients with persistent nasal GCC thinning. Six patients had no VF defect and showed statistically significant loss of GCC compared with controls (P = 0.001). Conclusions: Distinct patterns of GCC loss were identified in patients with chiasmal compression. Binasal GCC loss was typical and could be seen with minimal or no detectable VF loss. Thinning of the GCC may be detected before loss of the RNFL in some patients. After decompression, the majority of patients showed improvement in VF despite persistent GCC loss. Patients with less GCC loss before decompression had better postoperative VFs. Therefore, GCC analysis may be an objective method to diagnose and follow patients with chiasmal lesions.