Handheld Spectral-domain Optical Coherence Research Articles

Varied toxicity profile of intravitreal melphalan in two retinoblastoma eyes.

Retinoblastoma (RB) is the most common primary intraocular malignant tumor of childhood. Persistent or recurrent vitreous seeding is the most common reason for therapeutic failure in advanced RB. Intravitreal chemotherapy has emerged as an effective therapy for vitreous seeding in RB, with a generally acceptable safety profile. However, intravitreal chemotherapeutics, especially melphalan, can cause toxicity that may progress to total retinal atrophy. In this report, we present two cases with retinal melphalan toxicity that had varied clinical findings. One of the cases had extensive retinal atrophy that was demonstrated by hand-held spectral domain optical coherence tomography (HHSD-OCT), while the other had normal retinal anatomy on HHSD-OCT but markedly diminished retinal function on flash electroretinography.

Multivariate Models to Diagnose Early Referral-Warranted Retinopathy of Prematurity With Handheld Optical Coherence Tomography.

The purpose of this study was to create multivariate models predicting early referral-warranted retinopathy of prematurity (ROP) using non-contact handheld spectral-domain optical coherence tomography (OCT) and demographic data. Between July 2015 and February 2018, infants ≤1500 grams birth weight or ≤30 weeks gestational age from 2 academic neonatal intensive care units were eligible for this study. Infants were excluded if they were too unstable to participate in ophthalmologic examination (2), had inadequate image quality (20), or received prior ROP treatment (2). Multivariate models were created using demographic variables and imaging findings to identify early referral-warranted ROP (referral-warranted ROP and/or pre-plus disease) by routine indirect ophthalmoscopy. A total of 167 imaging sessions of 71 infants (45% male infants, gestational age 28.2+/-2.8 weeks, and birth weight 995.6+/-292.0 grams) were included. Twelve of 71 infants (17%) developed early referral-warranted ROP. The area under the receiver operating characteristic curve (AUC) was 0.94 for the generalized linear mixed model (sensitivity = 95.5% and specificity = 80.7%) and 0.83 for the machine learning model (sensitivity = 91.7% and specificity = 77.8%). The strongest variables in both models were birth weight, image-based Vitreous Opacity Ratio (an estimate of opacity density), vessel elevation, and hyporeflective vessels. A model using only birth weight and gestational age yielded an AUC of 0.68 (sensitivity = 77.3% and specificity = 63.4%), and a model using only imaging biomarkers yielded 0.88 (sensitivity = 81.8% and specificity = 84.8%). A generalized linear mixed model containing handheld OCT biomarkers can identify early referral-warranted ROP. Machine learning produced a less optimal model. With further validation, this work may lead to a better-tolerated ROP screening tool.

Posterior segment indications of handheld spectral domain optical coherence tomography in pediatric age group in a tertiary eye center in Egypt

Objective The aim of this study was to detect the posterior segment indications for the use of handheld optical coherence tomography in the pediatric age group. Patients and methods This was a retrospective observational study that included patients who were candidates for handheld spectral domain optical coherence tomography (HH-OCT) imaging for retinal or optic nerve (ON) diseases in Abo Elreesh hospital during the period from June 2018 to June 2022. The image, demographic, and clinical database of the included patients were reviewed. Data were tabulated using Microsoft Excel. Appropriate statistical methods were used to analyze and correlate the obtained data. Results A total of 189 patients were included in this study, comprising 109 (57.7%) male patients. The mean age was 7.2±3.9 (range: 0.2–16 years) years. Overall, 46 (24.3%) patients were less than 5 years of age (i.e. infants and preschool age). Patients who underwent HH-OCT scanning due to retinal causes (i.e. nystagmus, unexplained poor vision, uveitis, Coat's disease, trauma, and high myopia) were 130 (68.8%) patients, whereas 59 (31.2%) patients were indicated due to ON disease (i.e. primary congenital glaucoma and juvenile open angle glaucoma, optic disc hyperemia, swelling or pallor, and cases of large physiological cupping). Conclusion HH-OCT is a noninvasive feasible image modality for evaluation of retina and ON in infants and young children. The lack of a normative database for retinal nerve fiber layer thickness and ON head parameters in the pediatric age group in the device available in our service is considered a limitation in its use for proper evaluation of different pathologies involving the ON.

Severity of cystoid macular oedema in preterm infants observed using hand-held spectral domain optical coherence tomography improves weekly with postmenstrual age

ObjectiveTo investigate the relationship between cystoid macular oedema (CMO) measured in preterm infants using hand-held spectral domain optical coherence tomography (HH SD-OCT), with gestational age at birth (GA), birthweight (BW), diagnosis of retinopathy of prematurity (ROP) and the presence or absence of the external limiting membrane (ELM).MethodsWe conducted a prospective mixed cross-sectional/longitudinal observational study of 112 participants (23 to 36 weeks GA; n = 25 with, and n = 87 without, CMO). Retinal images were acquired using 344 HH SD-OCT (n = 66 with and n = 278 without, CMO) between 31 to 44 weeks postmenstrual age (PMA). CMO type (‘fovea’ and ‘dome’) was measured using thickness, width, area and peak.ResultsCMO was observed in 22.9% of preterm infants, and 19.2% of images. The mean values for thickness, width, area and peak of ‘dome’ CMO were 128.47 µm (SD +/- 34.23), 3624.45 µm (SD +/- 1323.03), 0.49 mm2 (SD +/- 0.28) and 279.81 µm (SD +/- 13.57) respectively. The mean values for thickness, width, area and peak of ‘fovea’ CMO were 64.37 µm (SD +/- 17.11), 2226.28 µm (SD +/- 1123.82), 0.16 mm2 (SD +/- 0.11) and 95.03 µm (SD +/- 26.99) respectively. Thickness, area width and peak were significantly greater for ‘dome CMO compared with ‘fovea’ CMO (P < 0.0001 for thickness, area and peak; P < 0.01 for width). Area and width significantly decreased with PMA for ‘dome’ and ‘fovea’ CMO (p = 0.0028; p < 0.001 respectively). No association was found between the presence of ROP and the detection of CMO or detection of CMO with absence of ELM.ConclusionsHH -OCT in preterm infants demonstrates that the severity of CMO appearance improves each week for both fovea and dome CMO.

Hand-held optical coherence tomography: Advancements in detection and assessment of optic nerve abnormalities and disease progression monitoring

Introduction Developmental abnormalities of the optic nerve (ON) and pediatric optic neuropathies such as glaucoma, are leading causes of childhood blindness. The recent development of hand-held spectral domain optical coherence tomography (HH-OCT) has enabled noncontact, high-resolution scanning in non-sedated newborns, infants and young children and has provided for the first time, in vivo visualization of the retina and ON in these patient groups. Areas covered This review will address the applications, recent advances and future potential of HH-OCT in diagnosis and monitoring of pediatric optic neuropathies. We will provide an update on the use of HH-OCT in pediatric glaucoma, congenital optic disc anomalies, optic pathway gliomas, optic atrophy and papilledema. Expert opinion HH-OCT could offer particular utility in children with optic neuropathies, by providing noninvasive, high-resolution characterization of the optic nerve head. Optic nerve parameters, such as retinal nerve fiber layer thickness, could serve as biomarkers to assess the severity of optic nerve disease qualitatively and quantitatively. Hence, HH-OCT is emerging as a powerful imaging tool to facilitate early diagnosis, identify prognostic biomarkers, monitor disease progression and assess response to treatment.

Segmentation of the foveal and parafoveal retinal architecture using handheld spectral-domain optical coherence tomography in children with Down syndrome.

Down syndrome is a common multigene, multisystem disorder associated with abnormalities of visual function and characteristic changes in the majority of tissues in the eye. Historic descriptions of macular structure in Down syndrome have been variable, but optical coherence tomography allows increasingly detailed characterization of retinal architecture in vivo. We demonstrate the feasibility of retinal imaging in children with Down syndrome using handheld OCT in an outpatient clinical setting, and describe the foveal and parafoveal retinal architecture in this group. Fourteen White British children aged between 4 and 11 with Down syndrome were recruited to have handheld SD-OCT retinal imaging performed at a single centre in an outpatient clinical setting. The thickness of the retinal layers at the fovea and parafovea was analysed using segmentation software, and compared with age-matched controls from a previously published normative UK dataset. Sixty-seven percent of the children studied had grade 1 foveal hypoplasia. At the fovea, the ganglion cell layer (p = 0.002) and inner nuclear layer (p < 0.001) were thickened relative to the control group. At the parafovea, there was thickening of the retina attributable to numerous layers in both the inner and outer retina, which remained significant after Bonferroni correction. OCT imaging of children with Down syndrome in an outpatient setting is feasible. There is a high incidence of foveal hypoplasia in this group, associated with thickening of the ganglion cell and inner nuclear layers at the fovea.

Assessment of macular edema after pediatric cataract and intraocular lens implantation surgery using handheld spectral domain optical coherence tomography

Assessment of macular edema after pediatric cataract and intraocular lens implantation surgery using handheld spectral domain optical coherence tomography

Vitreous findings quantified by handheld spectral domain optical coherence tomography correlate with retinopathy of prematurity severity

Vitreous findings quantified by handheld spectral domain optical coherence tomography correlate with retinopathy of prematurity severity

Clinical evaluation of torpedo maculopathy in an infant population with additional genetic testing for NEXMIF mutation.

To assess clinical characteristics of torpedo maculopathy (TM) lesions in an infant population with age ≤1.5 years and to investigate the role of NEXMIF mutation in the development of TM. Retrospective analysis of medical records of 17 consecutive infants with the diagnosis of TM between 2016 January and 2019 December were done. Fundus images and a hand-held spectral-domain optical coherence tomography (Envisu 2300, Bioptigen, Morrisville, NC, USA) were used to identify clinical characteristics of TM lesions. Additional molecular testing for mutation screening for NEXMIF gene was also carried out. Totally 55334 infants were screened during the study period and 17 (0.03%) were identified as having TM. The mean age at the time of diagnosis was 3.94±5.08 months. All TM lesions showed variable degrees of hypopigmentation. Satellite lesion in one infant was nasally located to the main TM lesion. Absence, disruption, loss, degeneration and/or irregularity of the ellipsoid zone were common findings on OCT examination. No pathogenic or likely pathogenic variant of NEXMIF gene was detected. Fundoscopic appearance and OCT findings of lesions show similarities to those already reported previously. Contrary to popular belief, a nasally located satellite lesion was observed in one of our case.

Dome-shaped macula in premature infants visualized by handheld spectral-domain optical coherence tomography

To describe dome-shaped macula and associated clinical findings in premature infants. This prospective, observational cohort study included a consecutive sample of premature infants screened for retinopathy of prematurity (ROP) with 9-month follow-up. Handheld spectral domain optical coherence tomography (SD-OCT) was performed at the time of ROP screening. Images were assessed for dome-shaped macula, cystoid macular edema, epiretinal membrane, vitreous bands, and punctate hyperreflective vitreous opacities. Dome height measurements were performed in a subset of images. Teller visual acuity and cycloplegic refraction were performed at an adjusted age of 8-10months. Of 37 infants (74 eyes; 49% male; mean gestational age 27.8±3.2weeks; mean birth weight 949±284g), 24/37 (65%) demonstrated dome-shaped macula in at least one eye (13 both eyes, 5 right eye only, and 6 left eye only). Of the 74 eyes, 26 (35%) could be reliably measured, with a mean dome height of 139.0±72.3μm (range, 54-369μm). Presence of dome-shaped macula was associated with a diagnosis of ROP (P=0.02; OR, 3.03; 95% CI, 1.18-7.82) and pre-plus or plus disease (P=0.02; OR, 4.20; 95% CI, 1.05-16.78). Infants with dome-shaped macula had lower birth weight compared with those without (877 vs 1081g; P=0.04). No associations with other demographics, OCT findings, and 9-month refractive outcomes were found. Dome-shaped macula was frequently identified by handheld SD-OCT in premature infants, especially those with lower birth weight and severe ROP. The long-term clinical significance of this finding is unknown.

In vivo dynamic characterization of the human tympanic membrane using pneumatic optical coherence tomography.

Decreased mobility of the human eardrum, the tympanic membrane (TM), is an essential indicator of a prevalent middle ear infection. The current diagnostic method to assess TM mobility is via pneumatic otoscopy, which provides subjective and qualitative information of subtle motion. In this study, a handheld spectral-domain pneumatic optical coherence tomography system was developed to simultaneously measure the displacement of the TM, air pressure inputs applied to a sealed ear canal, and to perform digital pneumatic otoscopy. A novel approach based on quantitative parameters is presented to characterize spatial and temporal variations of the dynamic TM motion. Furthermore, the TM motions of normal middle ears are compared with those of ears with middle ear infections. The capability of noninvasively measuring the rapid motion of the TM is beneficial to understand the complex dynamics of the human TM, and can ultimately lead to improved diagnosis and management of middle ear infections.

Understanding the variability of handheld spectral-domain optical coherence tomography measurements in supine infants.

PurposeCentral foveal thickness (CFT) measurements from optical coherence tomography (OCT) scans provide a precise measure of severity of pathologic changes in the fovea, progress of disease and response to treatment. Although these measures are additionally valuable to assess foveal development in infants, their reproducibility is not known. The goal of this retrospective study is to evaluate the variation and reproducibility of CFT measurements using handheld spectral-domain OCT (hh-SDOCT) in supine infants compared to conventional adult tabletop imaging.MethodsImaging sessions with multiple macular, volume scans in one eye were selected for analysis from two participant groups: Group 1, 25 imaging sessions from 21 preterm infants without macular edema imaged supine in the nursery using hh-SDOCT (Leica/Bioptigen Envisu C2300, RTP, NC); Group 2, 25 imaging sessions from 25 adults imaged using tabletop Bioptigen SDOCT. For each imaging session, three macular OCT volumes with acceptable image quality were selected for analysis. CFTs were measured using a customized script for automatic segmentation. An expert grader and a typical grader corrected the segmentation lines for the central foveal frame. Coefficient of variations (CV) and intraclass correlation coefficients (ICC) were calculated for graders and systems and compared to the previous literature on OCT reproducibility.ResultsCFT measurements were repeatable and reproducible for both handheld and tabletop SDOCT systems. For handheld, grader ICC (CI) and mean CV were 0.94 (0.90–0.97) and 3.8 (typical) and 0.98 (0.96–0.99) and 2.9 (expert), and for tabletop were 0.91(0.83–0.96) and 2.1 (typical) and 0.92 (0.86–0.96) and 1.9 (expert). Intergrader reproducibility of handheld and tabletop SDOCT systems were ICC(CI) 0.97 (0.95–0.98) and 0.93 (0.89–0.96) respectively, and both are comparable to previously reported reproducibility of tabletop systems.ConclusionHandheld SDOCT is a reproducible instrument to measure foveal thicknesses in supine infants. It can be used in clinical research to evaluate foveal changes during retinal development and pathological conditions.

HANDHELD SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS OF X-LINKED RETINOSCHISIS IN EARLY CHILDHOOD.

Using handheld spectral domain optical coherence tomography (SDOCT) imaging to investigate in vivo microanatomic retinal changes and their progression over time in young children with juvenile X-linked retinoschisis (XLRS). This retrospective analysis was of handheld SD OCT images obtained under a prospective research protocol in children who had established XLRS diagnosis based on genetic testing or clinical history. Three OCT graders performed standardized qualitative and quantitative assessment of retinal volume scans, which were divided into foveal, parafoveal, and extrafoveal regions. Visual acuity data were obtained when possible. Spectral domain OCT images were available of both eyes in 8 pediatric patients with ages 7 months to 10 years. The schisis cavities involved inner nuclear layer in over 90% (15/16) of eyes in all 3 regions. Retinal nerve fiber and ganglion cell layer involvement was present only in the extrafoveal region in 63% (10/16) eyes and outer nuclear and plexiform layer in few others. In 7 children followed over 2 months to 15 months, the location of schisis remained consistent. Central foveal thickness decreased from the baseline to final available visit in 4/6 eyes. Ellipsoid zone disruption seemed to accompany lower visual acuity in 1/4 eyes. Early in life, the SD OCT findings in XLRS demonstrate differences in schisis location in fovea-parafoveal versus extrafoveal region, possible association between poor visual acuity and degree of ellipsoid zone disruption and decrease in central foveal thickness over time in this group. Furthermore, they illustrates that the pattern of XLRS in adults is already present in very young children, and unlike in older children and adults, those presenting with earlier disease may have a more aggressive course. Further studies in this early age group may provide more insights into treatment and prevention of progressive visual impairment in children with XLRS.

Punctate hyperreflective vitreous opacities visualized by handheld spectral domain optical coherence tomography in premature infants screened for retinopathy of prematurity

Vitreous changes in retinopathy of prematurity (ROP) are poorly understood. The goal of this study was to characterize punctate hyperreflective vitreous opacities seen on handheld spectral domain optical coherence tomography (SD-OCT).

Comparison of hand-held spectral domain optical coherence tomography (HH-SDOCT) findings in nonaccidental injury (NAI) and non-NAI

We previously reported the utility of HH-SDOCT in identifying characteristic and unique vitreoretinal abnormalities not detected on clinical examination in children with NAI. The aim of this study was to compare HH-SDOCT findings in retinal haemorrhages of NAI and non-NAI and evaluate their usefulness in differentiating NAI from non-NAI.

Dome-shaped macula in infants screened for retinopathy of prematurity as seen by handheld spectral-domain optical coherence tomography

Dome-shaped macula in infants screened for retinopathy of prematurity as seen by handheld spectral-domain optical coherence tomography

HANDHELD SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IMAGING THROUGH THE UNDILATED PUPIL IN INFANTS BORN PRETERM OR WITH HYPOXIC INJURY OR HYDROCEPHALUS.

The authors investigated feasibility of undilated handheld spectral domain optical coherence tomography (SDOCT) retinal imaging in preterm infants and children with neurologic abnormalities. Under an institutional review board-approved protocol, the authors attempted handheld SDOCT imaging of the retina, choroid, and optic nerve in infants and young children without pupil dilation. Scans were analyzed for quality and successful capture of foveal, optic nerve, and retinal structural parameters and abnormalities. The authors obtained images through an undilated pupil of 11 infants/children over 28 eye imaging sessions, 27 at the bedside without sedation, and one under anesthesia. Infants had retinopathy of prematurity (n = 8), hypoxic ischemic encephalopathy (n = 2), or obstructive hydrocephalus (n = 1 child). Pupil sizes ranged from 1.0 mm to 3.5 mm. The authors captured fovea and optic nerve scans in 25/28 eye imaging sessions, with scans of adequate quality to discern prespecified foveal and optic nerve morphology, and of the 25 sessions, the choroidal-scleral junction was visible in all but 6 sessions. Undilated, handheld SDOCT imaging is a potential alternative method to evaluate the retina and optic nerve in patients with relative contraindication to pharmacological pupil dilation. This approach will enable the study of the eye-brain connection and ocular manifestations of neurologic diseases.

Handheld spectral domain optical coherence tomography (HH-SDOCT) findings in children with nonaccidental injury (NAI)

Handheld spectral domain optical coherence tomography (HH-SDOCT) findings in children with nonaccidental injury (NAI)

Demonstration of anatomical development of the human macula within the first 5years of life using handheld OCT.

To demonstrate the anatomical development of the human macula using handheld spectral domain optical coherence tomography (SD-OCT) during the first 5years of life. This study is a cross-sectional, observational case series. Thirty-five normal eyes of 35 full-term/late preterm infants and children under 5years of age were included. Handheld SD-OCT was used to image the macula of each eye. The data were analyzed using the Duke OCT Retinal Analysis Program v17 software. Retinal thickness maps were generated for the total retinal thickness (TRT), the inner retinal layers thickness (IRL), and the photoreceptor layer thickness (PRL). Based on the early treatment diabetic retinopathy study macular map, average thickness measurements were taken at 4 circles centered on the fovea (diameter): the foveal center (0.5mm), sector 1 (S1) (1mm), sector 2 (S2) (3mm), sector 3 (S3) (6mm). The median age at participation was 24months (range 5-52months). The TRT increased throughout the first 5years of life, and this increase was statistically significant at the foveal center and S1 (p = 0.01, p = 0.016, respectively). The IRL did not show any significant change in thickness from birth and throughout the first 5years of life. The PRL thickness showed thickening in the first 24months of age at the foveal center and S1 which was statistically significant at S1 (p = 0.066, p = 0.016, respectively). Interestingly, this PRL thickness increase plateaus beyond 24months of age. The photoreceptors inner segment/outer segment (IS/OS) band was identified as a distinct layer in all our subjects. Our findings conform with the literature that the anatomical development of the macular IRL completes before 5months of age and hence before the PRL. We also identify 24months of age as an important developmental milestone for photoreceptors development in the human macula.

Vitreous Bands Identified by Handheld Spectral-Domain Optical Coherence Tomography Among Premature Infants

Handheld spectral-domain optical coherence tomography (SD-OCT) can provide insights into the complex interactions occurring at the vitreoretinal interface in retinopathy of prematurity (ROP) to enhance our understanding of ROP pathology. To characterize vitreous bands in premature infants with use of handheld SD-OCT. Prospective cohort study conducted from July 7, 2015, to February 28, 2017, at 2 university-based neonatal intensive care units. Seventy-three premature infants who required routine ROP screening examination were recruited. Informed consent was obtained from all legal guardians. Trained graders who were masked to the clinical assessment analyzed each SD-OCT scan of the right eye for vitreoretinal findings. A third trained grader mediated disagreements. Associations between the presence of vitreous bands in premature infants with ROP diagnoses and the presence of other vitreoretinal SD-OCT findings were investigated. Of the 73 infants recruited, 6 infants' parents withdrew their children from the study, and 2 infants were too hemodynamically unstable for imaging, leaving a total of 65 participants. Of these, 32 (49%) were female, 36 (55%) were white, 10 (15%) were Hispanic, 3 (5%) were Native American, 4 (6%) were African American, 4 (7%) were Asian/Pacific Islander, and 8 (12%) were other. The mean (SD) gestational age was 28 (2.7) weeks, the mean (SD) birth weight was 997 g (286 g), and the mean (SD) postmenstrual age at imaging was 34 (3) weeks (mean [SD] total of 3 [2] imaging sessions). Comparing the 24 infants (37%) who had a right eye vitreous band at any time with the 41 (63%) who did not, no difference in mean birth weight, gestational age, postmenstrual age at imaging, sex, or race/ethnicity was identified. No associations with ROP stage (eg, in 6 [25%] infants with vitreous bands vs 4 [9.8%] in those without; P = .23), presence of plus disease (2 [8%] vs 2 [5%]; P = .84), or type 1 ROP (3 [12%] vs 3 [7%]; P = .66) were identified. Vitreous bands were associated with epiretinal membrane detected on SD-OCT (P = .001) with an odds ratio of 9.4 (95% CI, 2.8-31.3) in 15 [62%] infants with vitreous bands vs 6 [15%] in those without. Vitreous bands were also associated with cystoid macular edema (in 15 [62%] infants with vitreous bands vs 1 [27%] in those without; P = .005) with an odds ratio of 4.5 (95% CI, 1.5-13.3). In this study, the development of vitreous bands was associated with both cystoid macular edema and epiretinal membrane. These findings suggest a tractional pathogenesis to these entities among premature infants. This study did not find a direct association between vitreous bands and severe ROP. Additional study is needed to determine whether vitreous bands represent subclinical hyaloidal organization leading to retinal detachment in advanced ROP.