USE OF HAND-HELD OPTICAL COHERENCE TOMOGRAPHY DURING RETINOPATHY OF PREMATURITY SCREENING DEMONSTRATES AN INCREASED OUTER RETINA FROM EARLY POSTMENSTRUAL AGE IN PRETERM INFANTS WITH RETINOPATHY OF PREMATURITY.

PURPOSE: To identify structural markers of active retinopathy of prematurity (ROP) in foveal and parafoveal retinal layers using hand-held optical coherence tomography. METHODS: Hand-held optical coherence tomography images (n = 278) were acquired from a prospective mixed cross-sectional longitudinal observational study of 87 participants (23-36 weeks gestational age; n = 30 with ROP, n = 57 without ROP) between 31 and 44 weeks postmenstrual age excluding treated ROP and features of cystoid macular edema. Six retinal layer thicknesses from the fovea to the parafovea were analyzed at five locations up to 1,000 µ m, temporally and nasally. RESULTS: The mean outer retinal thickness during active ROP increased at the fovea and parafovea from postmenstrual age 33 weeks to 39 weeks ( P < 0.001), whereas the parafoveal inner nuclear layer and retinal nerve fiber layer reduced ( P < 0.001). Outer retinal thickness at the fovea from 33 weeks to 39 weeks postmenstrual age was consistently thicker in infants with ROP across all levels of prematurity (gestational age). CONCLUSION: Increased foveal and parafoveal outer retina measured using hand-held optical coherence tomography shows potential as a marker for ROP screening.

Diagnostic accuracy of retinal optical coherence tomography in children with a newly diagnosed brain tumour.

PURPOSE: To estimate the diagnostic accuracy of circumpapillary retinal nerve fibre layer (RNFL) thickness and macular ganglion cell layer-inner plexiform layer (GCL-IPL) thickness measurements to discriminate an abnormal visual function (i.e. abnormal age-based visual acuity and/or visual field defect) in children with a newly diagnosed brain tumour. METHODS: This cross-sectional analysis of a prospective longitudinal nationwide cohort study was conducted at four hospitals in the Netherlands, including the national referral centre for paediatric oncology. Patients aged 0-18 years with a newly diagnosed brain tumour and reliable visual acuity and/or visual field examination and optical coherence tomography were included. Diagnostic accuracy was evaluated with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: Of 115 patients included in the study (67 [58.3%] male; median age 10.6 years [range, 0.2-17.8 years]), reliable RNFL thickness and GCL-IPL thickness measurements were available in 92 patients (80.0%) and 84 patients (73.0%), respectively. The sensitivity for detecting an abnormal visual function was 74.5% for average RNFL thickness and 41.7% for average GCL-IPL thickness at a specificity of 44.5% and 82.9%, respectively. The PPV and NPV were 33.0% and 82.6% for the average RNFL thickness and 57.1% and 82.2% for the average GCL-IPL thickness. CONCLUSION: An abnormal visual function was discriminated correctly by using the average RNFL thickness in seven out of ten patients and by using the average GCL-IPL thickness in four out of ten patients. The relatively high NPVs signified that patients with normal average RNFL thickness and average GCL-IPL thickness measurements had a relative high certainty of a normal visual function.

Recognition of intracranial hypertension using handheld optical coherence tomography in children (RIO Study): a diagnostic accuracy study protocol.

INTRODUCTION: Paediatric intracranial hypertension (IH) is a rare but serious condition that can pose deleterious effects on the brain and vision. Estimating intracranial pressure (ICP) in children is difficult. Gold standard direct ICP measurement is invasive and carries risk. It is impractical to routinely perform direct ICP measurements over time for all children at risk of IH. This study proposes to assess the diagnostic accuracy of handheld optical coherence tomography (OCT), a non-invasive ocular imaging method, to detect IH in children. METHODS AND ANALYSIS: This is a prospective study evaluating the diagnostic accuracy of handheld OCT for IH in at risk children. Inclusion criteria include clinical and/or genetic diagnosis of craniosynostosis, idiopathic intracranial hypertension, space occupying lesion or other conditions association with IH and age 0-18 years old. Exclusion criteria include patients older than 18 years of age and/or absence of condition placing the child at risk of IH. The primary outcome measures are handheld OCT and 48-hour ICP assessments, which will be used for diagnostic accuracy testing (sensitivity, specificity, positive predictive value, negative predictive value and accuracy). Main secondary outcome measures include visual acuity, fundoscopic examination, contrast sensitivity, visual field testing and visual evoked potentials, wherever possible. ETHICS AND DISSEMINATION: Ethical approval was granted for this study by the East Midlands Nottingham 2 Research Ethics committee (UOL0348/IRAS 105137). Our findings will be disseminated through presentation at relevant meetings, peer-reviewed publication and via the popular media. TRIAL REGISTRATION NUMBER: ISRCTN52858719.

Cerebral malaria: insight into pathology from optical coherence tomography.

We aimed to investigate structural retinal changes in malarial retinopathy (MR) using hand-held optical coherence tomography (HH-OCT) to assess its diagnostic potential. Children with MR (n = 43) underwent ophthalmoscopy, fluorescein angiography and HH-OCT during admission, 1-month (n = 31) and 1-year (n = 8) post-discharge. Controls were comatose patients without malaria (n = 6) and age/sex-matched healthy children (n = 43). OCT changes and retinal layer thicknesses were compared. On HH-OCT, hyper-reflective areas (HRAs) were seen in the inner retina of 81% of MR patients, corresponding to ischaemic retinal whitening on fundus photography. Cotton wool spots were present in 37% and abnormal hyper-reflective dots, co-localized to capillary plexus, in 93%. Hyper-reflective vessel walls were present in 84%, and intra-retinal cysts in 9%. Vascular changes and cysts resolved within 48 h. HRAs developed into retinal thinning at 1 month (p = 0.027) which was more pronounced after 1 year (p = 0.009). Ischaemic retinal whitening is located within inner retinal layers, distinguishing it from cotton wool spots. Vascular hyper-reflectivity may represent the sequestration of parasitized erythrocytes in vessels, a key CM feature. The mechanisms of post-ischemic retinal atrophy and cerebral atrophy with cognitive impairment may be similar in CM survivors. HH-OCT has the potential for monitoring patients, treatment response and predicting neurological deficits.

Assessment of the anterior segment of patients with primary congenital glaucoma using handheld optical coherence tomography.

PURPOSE: To investigate the potential of handheld optical coherence tomography (HH-OCT) in assessing the anterior segment of the eye in patients with primary congenital glaucoma. DESIGN: A prospective, case-controlled observational study. PARTICIPANTS: Twenty-two patients with primary congenital glaucoma (PCG, 9 females and 13 males; mean age 4.36 ± 3.4 years) and age-, gender- and ethnicity-matched healthy participants. METHODS: Anterior OCT was performed in all participants using a high-resolution HH SD-OCT device (Envisu 2300, Leica Microsystems, Germany) without anaesthesia or sedation. RESULTS: Anterior HH-OCT in PCG visualised Haab's striae in 14.3%, uneven internal cornea in 9.5% and epithelial thickening in 11.9% of patients with central corneal thickening (CCT, p < 0.001). CCT was significantly correlated with the intraocular pressure (IOP, p < 0.001). The flat iris with a thin collarette zone was found in 59.5%, anterior iris insertion in 11.90% of eyes affected by PCG. Two independent examiners showed sensitivity and specificity of 87% and 77%, respectively, by instating iris thinning and flattening of the anterior profile. CONCLUSIONS: Anterior HH-OCT has significant potential to improve diagnosis and management of PCG. Clinically relevant information can be obtained non-invasively and without sedation. High specificity makes anterior HH-OCT an important adjunct for management of PCG. Excellent visualisation of the iris insertion on OCT indicates potential for AS OCT to assist with surgical planning, including decision on the type of surgery and location of the incision.

Pediatric Optical Coherence Tomography in Clinical Practice-Recent Progress.

PURPOSE: Optical coherence tomography (OCT) has revolutionized the diagnosis and management of adult retinal and optic nerve disease. Children were deprived of this technology until the recent development of handheld spectral-domain OCT (HH-SDOCT). In this article, we review the applications of OCT imaging in pediatric ophthalmology. METHODS: This study was a review of the literature. RESULTS: The acquisition and interpretation of pediatric tomograms differ significantly from those for adults, with adjustments needed to account for the shorter axial lengths, higher refractive errors, and ongoing retinal and optic nerve development in the pediatric eye. Handheld SDOCT is increasingly being used as an adjunctive diagnostic tool in retinopathy of prematurity (ROP) and nonaccidental injury (NAI) by providing additional morphologic information that is not normally clinically discernible. The role of HH-SDOCT in streamlining diagnosis in infantile nystagmus syndrome, retinal dystrophies, and degenerations has been established. Optical coherence tomography can also help differentiate between pediatric intraocular tumors, for example, hamartomas and retinoblastoma; monitor tumor progression; and monitor treatment response. In addition, HH-SDOCT is establishing its role as a noninvasive monitoring tool in children affected by optic nerve pathology such as glaucoma, optic nerve atrophy and hypoplasia, optic pathway glioma, and pseudotumor cerebri. CONCLUSIONS: Handheld SDOCT can provide novel insights into the natural history of retinal and optic nerve diseases in young children. For example, in achromatopsia and albinism, in vivo OCT studies have provided evidence of altered but ongoing retinal development in early childhood, which suggests that potentially targeting treatment at an earlier age may optimize visual function by normalizing retinal development.

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.

A randomized controlled trial comparing soft contact lens and rigid gas-permeable lens wearing in infantile nystagmus.

OBJECTIVE: To perform the first randomized controlled trial comparing soft contact lens (SCL) with rigid gas-permeable lens (RGPL) wearing in infantile nystagmus (IN), using spectacle wear as a baseline. DESIGN: Randomized, controlled cross-over trial with an intention-to-treat design. PARTICIPANTS AND CONTROLS: A total of 24 participants with IN (12 idiopathic, 12 with albinism). METHODS: Participants were randomized into 1 of 2 treatment arms receiving the following sequence of treatments (2-3 weeks for each treatment): (A) spectacles, SCL, RGPL, and spectacle wear; or (B) spectacles, RGPL, SCL, and spectacle wear. MAIN OUTCOME MEASURES: The main outcome measure was mean intensity of nystagmus at the null region viewing at 1.2 m. Secondary outcome measures included the same measure at 0.4 m viewing and across the horizontal meridian (measured over a ±30° range at 3° intervals) for distance and near. The nystagmus foveation characteristics were similarly assessed over ±30° and at the null region at 1.2 m and 0.4 m viewing. Visual outcome measures included best-corrected visual acuity (BCVA) at 4 m and 0.4 m, gaze-dependent visual acuity (GDVA) (i.e., visual acuity when maintaining gaze angles over a ±30° range at 10° intervals) at 4 m, and reading performance at 0.4 m derived from the Radner reading chart. RESULTS: There were no significant differences between SCL and RGPL wearing for any nystagmus characteristics or compared with spectacle wearing. The BCVA, reading acuity, and critical print size were significantly worse for SCL wearing compared with RGPL and baseline spectacle wear (P<0.05), although mean differences were less than 1 logarithm of the minimum angle of resolution (logMAR) line. CONCLUSIONS: Nystagmus was not significantly different during SCL and RGPL wearing in IN, and contact lens wearing does not significantly reduce nystagmus compared with baseline spectacle wearing. The wearing of SCL leads to a small but statistically significant deterioration in visual function compared with both RGPL and spectacle wearing at baseline, although mean effect sizes were not clinically relevant.

Horizontal and vertical look and stare optokinetic nystagmus symmetry in healthy adult volunteers.

PURPOSE: Look optokinetic nystagmus (OKN) consists of voluntary tracking of details in a moving visual field, whereas stare OKN is reflexive and consists of shorter slow phases of lower gain. Horizontal OKN is symmetrical in healthy adults, whereas symmetry of vertical OKN is controversial. Horizontal and vertical look and stare OKN symmetry was measured, and the consistency of individual asymmetries and the effect of varying stimulus conditions were investigated. METHODS: Horizontal and vertical look and stare OKN gains were recorded in 15 healthy volunteers (40 degrees /s) using new methods to delineate look and stare OKN. Responses with right and left eye viewing were compared to investigate consistency of individual OKN asymmetry. In a second experiment, the symmetry of stare OKN was measured in nine volunteers varying velocity (20 degrees /s and 40 degrees /s), contrast (50% and 100%), grating contrast profile (square or sine wave), and stimulus shape (full screen or circular vignetted). RESULTS: There was no horizontal or vertical asymmetry in look or stare OKN gain for all volunteers grouped together. However, individual vertical asymmetries were strongly correlated for left and right eye viewing (look: r = 0.77, P = 0.0008; stare: r = 0.75, P = 0.001) and for look and stare OKN (r = 0.66, P = 7.3 x 10(-5)) because of a strong correlation for downward moving stimuli (r = 0.73, P = 0.002). Horizontal and vertical asymmetries were not significantly affected by variations in stimulus parameter. CONCLUSIONS: Although no horizontal or vertical OKN asymmetries existed for volunteers grouped together, vertical OKN was characterized by idiosyncratic asymmetries that remained consistent for an individual. Look and stare OKN gain is strongly associated for downward moving stimuli.