Anastasia Pilat

In Vivo Foveal Development Using Optical Coherence Tomography

PURPOSE To characterize the time course of normal foveal development in vivo in term infants and young children using handheld spectral-domain optical coherence tomography (HH-SDOCT). METHODS We obtained 534 HH-SDOCT scans from 261 infants, children, and young adults with a mean age of 4.9 years (range, 0-27 years). Each retinal layer was manually segmented in ImageJ and correlated with gestational age (GA) and visual acuity (VA). The developmental trajectories of each retinal layer at the fovea, parafovea, and perifovea were calculated using fractional polynomial modeling. RESULTS The central macular thickness (CMT) increases logarithmically between birth and 48.6 months GA. The foveal ganglion cell (GCL), inner plexiform, inner nuclear (INL), and outer plexiform layers decrease in thickness exponentially until 18 months GA. Interestingly, the parafoveal and perifoveal GCL and INL thicknesses initially decrease until 17 months GA and then increase in thickness until 65.5 GA. The foveal outer nuclear layer, inner segment, and outer segment of the photoreceptors increase in thickness logarithmically until 32.4, 26.9, and 45.3 months GA, respectively. The parafoveal and perifoveal outer retinal layers increase in thickness more gradually until 146 months GA. The thickness of the outer retinal layers and CMT were strongly correlated with VA, with r = 0.54 (P < 0.0001) and r = 0.52 (P < 0.0001), respectively. CONCLUSIONS We have modeled for the first time the complex, nonlinear developmental trajectories for each retinal layer and demonstrate that development continues until adolescence. Our description of normal development will be helpful in diagnosing, monitoring, and understanding pediatric retinal disease.

High resolution imaging of the optic nerve and retina in optic nerve hypoplasia

Purpose To investigate the optic nerve and macular morphology in patients with optic nerve hypoplasia (ONH) using spectral-domain optical coherence tomography (SD OCT). Design Prospective, cross-sectional, observational study. Subjects A total of 16 participants with ONH (10 female and 6 male; mean age, 17.2 years; 6 bilateral involvement) and 32 gender-, age-, ethnicity-, and refraction-matched healthy controls. Methods High-resolution SD OCT (Copernicus [Optopol Technology S.A., Zawiercie, Poland], 3 μm resolution) and handheld SD OCT (Bioptigen Inc [Research Triangle Park, NC], 2.6 μm resolution) devices were used to acquire horizontal scans through the center of the optic disc and macula. Main Outcome Measures Horizontal optic disc/cup and rim diameters, cup depth, peripapillary retinal nerve fiber layer (RNFL), and thickness of individual retinal layers in participants with ONH and in controls. Results Patients with ONH had significantly smaller discs (P < 0.03 and P < 0.001 compared with unaffected eye and healthy controls, respectively), horizontal cup diameter (P < 0.02 for both), and cup depth (P < 0.02 and P < 0.01, respectively). In the macula, significantly thinner RNFL (nasally), ganglion cell layer (GCL) (nasally and temporally), inner plexiform layer (IPL) (nasally), outer nuclear layer (ONL) (nasally), and inner segment (centrally and temporally) were found in patients with ONH compared with the control group (P < 0.05 for all comparisons). Continuation of significantly thicker GCL, IPL, and outer plexiform layer in the central retinal area (i.e., foveal hypoplasia) was found in more than 80% of patients with ONH. Clinically unaffected fellow eyes of patients with ONH showed mild features of underdevelopment. Visual acuity and presence of septo-optic dysplasia were associated with changes in GCL and IPL. Sensitivity and specificity for the detection of ONH based on disc and retinal optical coherence tomography (OCT) parameters were >80%. Conclusions Our study provides evidence of retinal changes in ONH. In addition to thinning of retina layers mainly involving the RNFL and GCL, signs reminiscent of foveal hypoplasia were observed in patients with ONH. Optic nerve and foveal parameters measured using OCT showed high sensitivity and specificity for detecting ONH, demonstrating their useful for clinical diagnosis.

Normal macular structure measured with optical coherence tomography across ethnicity

Objective The difference in prevalence of various retinal pathologies in people of different ethnicity is well established. Optical coherence tomography (OCT) is a widely used technique that allows quantitative analysis of macular structure. In this study, we investigated macular layer morphology in healthy subjects using high-resolution spectral domain (SD) OCT across ethnicities comparing Asian (ie, Indian subcontinent) and Caucasian individuals. Methods 133 healthy volunteers (67—Asian, 66—Caucasian) were examined using SD-OCT. Average retinal and nerve fibre layer thickness were measured in a semiautomated way. Analysis of the measurements of each retinal layer at the macula was quantified using tomograms obtained by SD-OCT. Results In this study, we find significant difference in macular structure in Asian and Caucasian participants. Caucasian subjects have thicker inner segment (p=0.015 in the central region), outer segment (p=0.04 in the temporal region) and outer nuclear (p=0.021 and p=0.03 for the central and temporal regions, respectively) layers, while Asians demonstrate thicker retinal pigment epithelial layer (p=0.004 for the temporal region). Conclusions Differences in macular morphology due to ethnicity should be considered in determining control values for diagnostic purposes, and can be used to guide future studies in risk and prognosis for macular pathologies.

In Vivo Morphology of the Optic Nerve and Retina in Patients With Parkinson's Disease

Purpose To investigate optic nerve (ON) and macular morphology in patients with Parkinsons disease (PD) using spectral-domain optical coherence tomography (SD-OCT). Subjects Twenty-five participants with PD (19 males and 6 females; mean age 60.79; SD ± 9.24) and 25 sex-, age-, ethnicity-, and refraction-matched healthy controls. Methods A high-resolution SD-OCT device was used to acquire scans in 25 participants with PD (mean age 60.79; ± SD 9.24) and 25 sex-, age-, ethnicity-, and refraction-matched healthy controls. Main outcome measures included optic nerve head parameters (disc/cup diameters/areas, cup/rim volumes, cup depth, cup/disc ratio; peripapillary retinal nerve fiber layer [ppRNFL] thickness), retinal thickness (in inner and outer annuli around the foveal center) and thickness of individual retinal layers. Results Our study showed significant ppRNFL thinning in PD patients in all quadrants (P < 0.05) associated with a shallower optic cup (P = 0.03) as compared with controls. Foveal remodelling with retinal thinning (nasal and temporal segments in both annuli; and superior segment in outer annulus; P < 0.05), foveal pit widening (P = 0.05), central outer plexiform layer (OPL) thickening (P < 0.001), and nasal RPE thinning (P < 0.001) was also found in PD. The differences were more obvious in hemiretinae related to the predominantly affected cerebral hemisphere. Changes were more pronounced in advanced stages and longer PD duration. Conclusions Optic nerve changes in PD are likely to be caused by primary neurodegeneration. Central retinal thinning, pit widening, central OPL thickening, and RPE thinning indicate foveal remodelling. Specific changes of the fovea and thinning of individual retinal layers, correlating with disease severity and duration, indicate that ON and retinal changes have potential to be used as biomarkers for PD.

Macular Morphology in Patients with Optic Nerve Head Drusen and Optic Disc Edema

PURPOSE In this study we investigated macular morphology, including individual retinal layers, in patients with optic nerve head drusen (ONHD) and optic disc edema (ODE) compared with healthy participants, using high-resolution spectral domain optical coherence tomography (OCT). DESIGN Prospective, cross-sectional, observational study. PARTICIPANTS A total of 67 patients with ONHD, 36 patients with ODE, and 57 healthy participants. METHODS High-resolution spectral domain OCT (Copernicus [OPTOPOL Technology S.A., Zawiercie, Poland] 3-μm resolution, 7 × 7 × 2-mm volumetric scans) was used to image macula morphology. Average retinal nerve fiber layer (RNFL) thickness was measured using a semiautomated method with manual correction of the internal limiting membrane, RNFL, and retinal pigment epithelium (RPE). Retinal and RNFL thicknesses were measured and analyzed in 3 circular zones (Early Treatment Diabetic Retinopathy Study protocol). Individual retinal layers at the macula were quantified by analyzing tomograms using ImageJ (http://rsbweb.nih.gov/ij/; Accessed June 1, 2013). MAIN OUTCOME MEASURES Average retinal and individual retinal layer thickness in patients with ODE or ONHD, and healthy controls. RESULTS Patients with ONHD had thicker retinae in the inner annulus compared with patients with ODE and controls (significant in the temporal segment compared with those with ODE [P = 0.013] and in the superior segment compared with controls [P = 0.05]). Patients with ONHD had a significantly thinner inner plexiform layer (IPL) (P = 0.02), nerve fiber layer (P = 0.05), and RPE (P = 0.0001), and thicker ganglion cell layer (P = 0.003) and outer plexiform layer (OPL) (P < 0.001) compared with controls. Patients with ODE demonstrated the thickest retina and RNFL in the outer annulus (significant in the inferior segment compared with controls, P = 0.02 for both) with significant thickening in the IPL (P = 0.004), OPL (P < 0.003), and outer segment layer (P ≤ 0.02), and severe ganglion cell loss (P = 0.004) and RPE (P = 0.0001) thinning compared with healthy volunteers. CONCLUSIONS Our study shows that optic nerve diseases are associated with selective changes in different retinal layers in patients with ODE and ONHD. These findings may be of diagnostic value and could be taken into consideration in assessing patients and studying the pathogenesis of these conditions.

Retinal development in albinism: a prospective study using optical coherence tomography in infants and young children.

BACKGROUND Retinal development normally involves migration of the inner retinal layers away from the fovea, migration of the cone photoreceptors into the fovea, and elongation of the photoreceptors over time. This process is arrested prematurely in albinism. However, because retinal development continues at least until the age of 4 years, when development arrests in albinism is uncertain. In this study we outlined the time course of retinal development in children with albinism. METHODS We studied 44 children with a diagnosis of albinism and 223 control participants. All participants were aged between 0 and 6 years. We obtained 219 mixed cross-sectional and longitudinal optical coherence tomography examinations in the albinism group and compared them with 558 control examinations. Retinal layer segmentation was performed with ImageJ software. Generalised linear mixed regression modelling was used to analyse group differences in retinal development. FINDINGS In the albinism group, inner retinal layer migration from the fovea was delayed and arrested prematurely, resulting in a significantly thicker central macular thickness than in the control group (p<0·0001). Whereas the central macular thickness increased with age in the control group, in the albinism group it initially decreased with age as a result of continuing regression of the inner retinal layers (p=0·041). The perifoveal retinal thickness was significantly decreased in albinism from a reduction of both inner (p<0·0001) and outer (p<0·0001) retinal layer thicknesses. There was evidence that the photoreceptor layers across the fovea were elongating in albinism, albeit at a reduced rate, compared with the control group. This difference was most apparent for the foveal photoreceptor inner segment (p=0·001). INTERPRETATION Our findings show that perturbations exist in several aspects of retinal development including the migration and differentiation of the neuronal cells within the retina. We showed continuing regression of the inner retinal layers and elongation of the photoreceptor layers suggesting residual plasticity of the developing albino retina. This finding is important because treatment at the earliest stages of the condition might normalise retinal development and optimise vision. FUNDING UK Medical Research Council (grant number MR/J004189/1), Ulverscroft Foundation, National Eye Research Centre, Nystagmus Network UK.

Morphology of Retinal Vessels in Patients With Optic Nerve Head Drusen and Optic Disc Edema

PURPOSE We quantitatively investigated the peripapillary vascular morphology in patients with optic nerve head drusen (ONHD) and optic disc edema (ODE). METHODS Computer-based fundus analysis was used to investigate peripapillary vascular morphology, including length, branching, and diameter of arteries and veins calibrated by optical coherence tomography. RESULTS Patients with ONHD showed significantly larger diameters of arteries without branching (P = 0.05), and arteries after primary/before secondary branching (P = 0.04) and secondary venous branching started closer to the optic disc (P = 0.03) compared to healthy controls. The ODE patients had significantly reduced number of small peripapillary veins and larger number of veins without branching compared to ONHD and controls (P = 0.02). Anomalous branching with arterial and venous trifurcation presented in the ODE and ONHD groups, with significant higher prevalence in ODE patients for venous trifurcations compared to ONHD and controls (P = 0.02). CONCLUSIONS The diameter of vessels in ONHD patients were significantly larger in arteries without branching (P = 0.05), after primary branching (P = 0.04), and venous branching closer to the disc area (P = 0.03) compared to controls. The ODE patients demonstrated widening of the small peripapillary veins measured by a significantly larger number of veins without branching (P = 0.001 and P = 0.02, compared to controls and ONHD, respectively) and less small veins (P = 0.001 and P = 0.04, compared to controls and ONHD, respectively).

Characterization of Abnormal Optic Nerve Head Morphology in Albinism Using Optical Coherence Tomography.

PURPOSE To characterize abnormalities in three-dimensional optic nerve head (ONH) morphology in people with albinism (PWA) using spectral-domain optical coherence tomography (SD-OCT) and to determine whether ONH abnormalities relate to other retinal and clinical abnormalities. METHODS Spectral-domain OCT was used to obtain three-dimensional images from 56 PWA and 60 age- and sex-matched control subjects. B-scans were corrected for nystagmus-associated motion artefacts. Disc, cup, and rim ONH dimensions and peripapillary retinal nerve fiber layer (ppRNFL) thickness were calculated using Copernicus and ImageJ software. RESULTS Median disc areas were similar in PWA (median = 1.65 mm2) and controls (1.71 mm2, P = 0.128), although discs were significantly elongated horizontally in PWA (P < 0.001). In contrast, median optic cup area in PWA (0.088 mm2) was 23.7% of that in controls (0.373 mm2, P < 0.001), with 39.4% of eyes in PWA not demonstrating a measurable optic cup. This led to significantly smaller cup to disc ratios in PWA (P < 0.001). Median rim volume in PWA (0.273 mm3) was 136.6% of that in controls (0.200 mm3). The ppRNFL was significantly thinner in PWA compared with controls (P < 0.001), especially in the temporal quadrant. In PWA, ppRNFL thickness was correlated to ganglion cell thickness at the central fovea (P = 0.007). Several ONH abnormalities, such as cup to disc ratio, were related to higher refractive errors in PWA. CONCLUSIONS In PWA, ocular maldevelopment is not just limited to the retina but also involves the ONH. Reduced ppRNFL thickness is consistent with previous reports of reduced ganglion cell numbers in PWA. The thicker rim volumes may be a result of incomplete maturation of the ONH.

Hand-held optical coherence tomography imaging in children with anterior segment dysgenesis

Case 1: A 5-year-old patient was seen because of conjunctivitis. An irregular circular white structure located underneath of the endothelium anteriorly to the limbus was found incidentally (Fig. 2). Diagnosis of Axenfeld’s anomaly was made. Optical coherence tomography (OCT) angle scans demonstrated a prominent anteriorly displaced Schwalbe line. The patient had several small (less than 1 mm) zones of the iridocorneal adhesions originating from the angular part of the iris and fixed behind the displaced Schwalbe line (Fig. 2E, right) in both eyes.

Retinal and optic nerve changes in microcephaly: An optical coherence tomography study.

Objective To investigate the morphology of the retina and optic nerve (ON) in microcephaly. Methods This was a prospective case-control study including 27 patients with microcephaly and 27 healthy controls. All participants underwent ophthalmologic examination and handheld optical coherence tomography (OCT) of the macula and ON head. The thickness of individual retinal layers was quantified at the foveal center and the parafovea (1,000 μm nasal and temporal to the fovea). For the ON head, disc diameter, cup diameter, cup-to-disc ratio, cup depth, horizontal rim diameter, rim area, peripapillary retinal thickness, and retinal nerve fiber layer thickness were measured. Results Seventy-eight percent of patients had ophthalmologic abnormalities, mainly nystagmus (56%) and strabismus (52%). OCT abnormalities were found in 85% of patients. OCT revealed disruption of the ellipsoid zone, persistent inner retinal layers, and irregular foveal pits. Parafoveal retinal thickness was significantly reduced in patients with microcephaly compared to controls, nasally (307 ± 44 vs 342 ± 19 μm, p = 0.001) and temporally (279 ± 56 vs 325 ± 16 μm, p < 0.001). There was thinning of the ganglion cell layer and the inner segments of the photoreceptors in microcephaly. Total peripapillary retinal thickness was smaller in patients with microcephaly compared to controls for both temporal (275 vs 318 μm, p < 0.001) and nasal sides (239 vs 268 μm, p = 0.013). Conclusions Retinal and ON anomalies in microcephaly likely reflect retinal cell reduction and lamination alteration due to impaired neurogenic mitosis. OCT allows diagnosis and quantification of retinal and ON changes in microcephaly even if they are not detected on ophthalmoscopy.