Outer Retinal Structure in Best Vitelliform Macular Dystrophy

Importance Demonstrating the utility of adaptive optics scanning light ophthalmoscopy (AOSLO) to assess outer retinal structure in Best vitelliform macular dystrophy (BVMD). Objective To characterize outer retinal structure in BVMD using spectral-domain optical coherence tomography (SD-OCT) and AOSLO. Design, Setting, and Participants Prospective, observational case series. Four symptomatic members of a family with BVMD with known BEST1 mutation were recruited at the Advanced Ocular Imaging Program research lab at the Medical College of Wisconsin Eye Institute, Milwaukee. Intervention Thickness of 2 outer retinal layers corresponding to photoreceptor inner and outer segments was measured using SD-OCT. Photoreceptor mosaic AOSLO images within and around visible lesions were obtained, and cone density was assessed in 2 subjects. Main Outcome and Measure Photoreceptor structure. Results Each subject was at a different stage of BVMD, with photoreceptor disruption evident by AOSLO at all stages. When comparing SD-OCT and AOSLO images from the same location, AOSLO images allowed for direct assessment of photoreceptor structure. A variable degree of retained photoreceptors was seen within all lesions. The photoreceptor mosaic immediately adjacent to visible lesions appeared contiguous and was of normal density. Fine hyperreflective structures were visualized by AOSLO, and their anatomical orientation and size were consistent with Henle fibers. Conclusions and Relevance The AOSLO findings indicate that substantial photoreceptor structure persists within active lesions, accounting for good visual acuity in these patients. Despite previous reports of diffuse photoreceptor outer segment abnormalities in BVMD, our data reveal normal photoreceptor structure in areas adjacent to clinical lesions. This study demonstrates the utility of AOSLO for understanding the spectrum of cellular changes that occur in inherited degenerations such as BVMD. Photoreceptors are often significantly affected at various stages of inherited degenerations, and these changes may not be readily apparent with current clinical imaging instrumentation

The Reliability of Parafoveal Cone Density Measurements

Background Adaptive optics scanning light ophthalmoscopy (AOSLO) enables direct visualisation of the cone mosaic, with metrics such as cone density and cell spacing used to assess the integrity or health of the mosaic. Here we examined the interobserver and inter-instrument reliability of cone density measurements. Methods For the interobserver reliability study, 30 subjects with no vision-limiting pathology were imaged. Three image sequences were acquired at a single parafoveal location and aligned to ensure that the three images were from the same retinal location. Ten observers used a semiautomated algorithm to identify the cones in each image, and this was repeated three times for each image. To assess inter-instrument reliability, 20 subjects were imaged at eight parafoveal locations on one AOSLO, followed by the same set of locations on the second AOSLO. A single observer manually aligned the pairs of images and used the semiautomated algorithm to identify the cones in each image. Results Based on a factorial study design model and a variance components model, the interobserver study\u27s largest contribution to variability was the subject (95.72%) while the observer\u27s contribution was only 1.03%. For the inter-instrument study, an average cone density intraclass correlation coefficient (ICC) of between 0.931 and 0.975 was calculated. Conclusions With the AOSLOs used here, reliable cone density measurements can be obtained between observers and between instruments. Additional work is needed to determine how these results vary with differences in image quality

Assessing Retinal Structure In Complete Congenital Stationary Night Blindness and Oguchi Disease

Purpose To examine retinal structure and changes in photoreceptor intensity after dark adaptation in patients with complete congenital stationary night blindness and Oguchi disease. Design Prospective, observational case series. Methods We recruited 3 patients with complete congenital stationary night blindness caused by mutations in GRM6, 2 brothers with Oguchi disease caused by mutations in GRK1, and 1 normal control. Retinal thickness was measured from optical coherence tomography images. Integrity of the rod and cone mosaic was assessed using adaptive optics scanning light ophthalmoscopy. We imaged 5 of the patients after a period of dark adaptation and examined layer reflectivity on optical coherence tomography in a patient with Oguchi disease under light- and dark-adapted conditions. Results Retinal thickness was reduced in the parafoveal region in patients with GRM6 mutations as a result of decreased thickness of the inner retinal layers. All patients had normal photoreceptor density at all locations analyzed. On removal from dark adaptation, the intensity of the rods (but not cones) in the patients with Oguchi disease gradually and significantly increased. In 1 Oguchi disease patient, the outer segment layer contrast on optical coherence tomography was 4-fold higher under dark-adapted versus light-adapted conditions. Conclusions The selective thinning of the inner retinal layers in patients with GRM6 mutations suggests either reduced bipolar or ganglion cell numbers or altered synaptic structure in the inner retina. Our finding that rods, but not cones, change intensity after dark adaptation suggests that fundus changes in Oguchi disease are the result of changes within the rods as opposed to changes at a different retinal locus

Dissociation Chemistry of 3‑Oxetanone in the Gas Phase

3-Oxetanone is a strained cyclic molecule which plays an important role in synthetic chemistry. A few studies exist in the literature about the equilibrium properties of this molecule and the dissociation patterns of substituted 3-oxetanones. For the unsubstituted 3-oxetanone, formation of ketene (CH₂CO) and formaldehyde (HCHO) was considered to be the major dissociation pathway. In a recent work, pyrolysis products of 3-oxetanone molecule in the gas phase were investigated by Fourier transform infrared spectroscopy and photoionization mass spectrometry. In this study, an additional dissociation channel forming ethylene oxide (c-C₂H₄O) and carbon monoxide CO was reported. In the present work, gas phase dissociation chemistry of 3-oxetanone was investigated by electronic structure theory, <i>ab initio</i> classical chemical dynamics simulations, and Rice–Ramsperger–Kassel–Marcus (RRKM) rate constant calculations. The barrier height for the ethylene oxide channel was found to be much higher than the ketene pathway. The dynamics simulations were performed at three different total energies, viz., 150, 200, and 300 kcal/mol, and multiple reaction pathways and varying branching ratios observed. A new dissociation channel involving a ring-opened isomer of ethylene oxide was identified in the simulations. This pathway has a lower energy barrier and was dominant in our dynamics simulations

Evaluation of normal human foveal development using optical coherence tomography and histologic examination

Objective: To assess outer retinal layer maturation during late gestation and early postnatal life using optical coherence tomography and histologic examination. Methods: Thirty-nine participants 30 weeks' postmenstrual age or older were imaged using a handheld optical coherence tomography system, for a total of 102 imaging sessions. Foveal images from 16 participants (21 imaging sessions) were normal and evaluated for inner retinal excavation and the presence of outer retinal reflective bands. Reflectivity profiles of central, parafoveal, and parafoveal retina were extracted and were compared with age-matched histologic sections. Results: The foveal pit morphologic structure in infants was generally distinguishable from that in adults. Reflectivity profiles showed a single hyperreflective band at the fovea in all the infants younger than 42 weeks' postmenstrual age. Multiple bands were distinguishable in the outer retina at the peri fovea by 32 weeks' postmenstrual age and at the fovea by 3 months' postterm. By 17 months' postnatal, the characteristic appearance of 4 hyperreflective bands was evident across the foveal region. These features are consistent with previous results from histologic examinations. A "temporal divot" was present in some infants, and the foveal pit morphologic structure and the extent of inner retinal excavation were variable. Conclusions: Handheld optical coherence tomography is a viable technique for evaluating neonatal retinas. In premature infants who do not develop retinopathy of prematurity, the foveal region seems to follow a developmental time course similar to that associated with in utero maturation. Clinical Relevance: As pediatric optical coherence tomography becomes more common, a better understanding of normal foveal andmacular development is needed. Longitudinal imaging offers the opportunity to track postnatal foveal development among preterm infants in whom poor visual outcomes are anticipated or to follow up treatment outcomes in this population

Multidisciplinary Ophthalmic Imaging RefMoB, a Reflectivity Feature Model-Based Automated Method for Measuring Four Outer Retinal Hyperreflective Bands in Optical Coherence Tomography

Citation: Ross DH, Clark ME, Godara P, et al. RefMoB, a reflectivity feature model-based automated method for measuring four outer retinal hyperreflective bands in optical coherence tomography. Invest Ophthalmol Vis Sci. 2015;56:4166-4176. DOI:10.1167/iovs.14-15256 PURPOSE. To validate a model-driven method (RefMoB) of automatically describing the four outer retinal hyperreflective bands revealed by spectral-domain optical coherence tomography (SDOCT), for comparison with histology of normal macula; to report thickness and position of bands, particularly band 2 (ellipsoid zone [EZ], commonly called IS/OS). METHODS. Foveal and superior perifoveal scans of seven SDOCT volumes of five individuals aged 28 to 69 years with healthy maculas were used (seven eyes for validation, five eyes for measurement). RefMoB determines band thickness and position by a multistage procedure that models reflectivities as a summation of Gaussians. Band thickness and positions were compared with those obtained by manual evaluators for the same scans, and compared with an independent published histological dataset. RESULTS. Agreement among manual evaluators was moderate. Relative to manual evaluation, RefMoB reported reduced thickness and vertical shifts in band positions in a band-specific manner for both simulated and empirical data. In foveal and perifoveal scans, band 1 was thick relative to the anatomical external limiting membrane, band 2 aligned with the outer one-third of the anatomical IS ellipsoid, and band 3 (IZ, interdigitation of retinal pigment epithelium and photoreceptors) was cleanly delineated. CONCLUSIONS. RefMoB is suitable for automatic description of the location and thickness of the four outer retinal hyperreflective bands. Initial results suggest that band 2 aligns with the outer ellipsoid, thus supporting its recent designation as EZ. Automated and objective delineation of band 3 will help investigations of structural biomarkers of dark-adaptation changes in aging. Keywords: optical coherence tomography, reflectivity, segmentation, retina, ellipsoid, interdigitation, photoreceptors, retinal pigment epithelium, age-related macular degeneration S pectral-domain optical coherence tomography (SDOCT) is an interferometry technique that uses low coherence light to achieve depth-resolved, comprehensive, and noninvasive cross-sectional views of chorioretinal structure in vivo. 5 By assuming that the ELM and RPE-BrM bands were correctly designated, we found that band 2 closely aligned with the IS ellipsoid (ISel), a conclusion supported by direct imaginghistology correlations in laboratory animals. 5 These fine processes, up to 15 lm long, form a candelabra-like arrangement with cone OS, which are shorter than rod OS. Othe