Fundus-Controlled Dark Adaptometry in Young Children Without and With Spontaneously Regressed Retinopathy of Prematurity.

PURPOSE: We correlate dark adaptation course with foveal morphologic alterations in preterm and term-born children using a modified fundus-controlled perimeter and spectral domain-optical coherence tomography (SD-OCT) imaging. METHODS: We performed fundus-controlled chromatic dark adaptometry in premature children aged 6 to 13 years without retinopathy of prematurity (no-ROP; n = 61) and with spontaneously regressed ROP (sr-ROP, n = 29), and in 11 age-matched term-born children. The degree of macular developmental arrest (MDA), defined as a disproportion of the outer nuclear layer to inner retinal layers in the fovea (ONL+/IRL-ratio), was analyzed with the DiOCTA tool in SD-OCT scans. RESULTS: Children with MDA showed a flatter dark adaptation course progression with a significant rod-mediated sensitivity recovery delay (0.0113 vs. 0.0253 dB/s; P < 0.001). Preterm-born children with regular foveal morphology reached the final rod-mediated dark-adapted threshold at 12 minutes after bleach at 18.8 dB, compared to after 18.7 minutes at 17.6 dB in children with MDA (no significant difference in final threshold; P = 0.773). The cone-mediated dark adaptation progression showed a significant lower final threshold in children with MDA (6.0 vs. 8.1 dB; P = 0.004). CONCLUSIONS: Changes in dark adaptation were seen in the presence of MDA observed in premature children in the no-ROP and sr-ROP groups. MDA in former premature children is associated with functional deficits of cone and rod photoreceptor visual pathways. TRANSLATIONAL RELEVANCE: Morphologic alterations in the central retina of premature children, evident in SD-OCT, are associated with long-term functional deficits in the rod and cone pathways, particularly evident in the rod dark adaptation course measured at 12° eccentricity. This indicates a more widespread retinal functional pathology not limited to the fovea, but occurring together with foveal alterations best defined as MDA.

Cone-Mediated Function Correlates to Altered Foveal Morphology in Preterm-Born Children at School Age.

Purpose: To correlate cone- and rod-mediated function with morphology of the macula in preterm-born children without and with spontaneously regressed retinopathy of prematurity (ROP). Methods: We performed spectral-domain optical coherence tomography (SD-OCT) single scans in the macular center of preterm-born children aged 6 to 12 years (mean ± SD, 7.4 ± 1.8) without ROP (noROP; n = 59) and with spontaneously regressed ROP (srROP; n = 34), documented with wide-angle digital imaging during routine screening for acute ROP, and compared the data from 14 age-matched term-born children. SD-OCT data were compared to functional cone- and rod-mediated results of scotopic and photopic chromatic pupillometry (cP) and two-color fundus-controlled perimetry (2C-FCP). Results: SD-OCT showed a shallowed foveal pit with significantly reduced outer nuclear layer to inner retinal layer ratio, indicating macular developmental arrest (MDA). MDA was present in 44% of the srROP and 27% of the noROP children. Pupil reaction to photopic red stimuli on blue background showed significantly lower values in all preterm-born children with MDA. In accordance, photopic light increment sensitivity (LIS) to red stimuli in the foveal center on the 2C-FCP was also significantly reduced in children with MDA. Under scotopic conditions, no significant differences were apparent in both pupil reaction with cP and LIS with 2C-FCP. Conclusions: Both objective pupillary response to cone-mediated photopic red stimuli and subjective central cone-mediated results in fundus-controlled perimetry were reduced in preterm-born children with MDA. MDA was present in a significant number of patients with srROP, but also without ROP.

Choroidal Thickness with Swept-Source Optical Coherence Tomography versus Foveal Morphology in Young Children with a History of Prematurity.

AIM: Comparison of choroidal thickness (CT) and foveal morphology as seen with swept-source optical coherence tomography (SS-OCT) in children with a history of treated or spontaneously regressed retinopathy of prematurity (tROP or srROP) to assess the impact on best-corrected visual acuity (BCVA). METHODS: CT was measured by SS-OCT (DRI-OCT Triton; Topcon, USA) single scans of a 6-mm diameter around the fovea in 17 children with tROP or srROP (4-7 years of age) and compared to 25 controls (age-matched children and adults). The disproportion of the outer nuclear layer and inner retinal layers at the fovea (i.e., the ONL+/IRL ratio) as a measure of macular developmental arrest (MDA) was manually analyzed. BCVA was tested with ETDRS letter charts and correlated with the morphology. RESULTS: CT was significantly thinner in children with tROP and srROP compared to term-born healthy children (nKids) at all measurement marks (p < 0.001), and mostly affected in the subfoveal area. tROP showed the lowest CT. CT allowed no direct conclusion about ONL+/IRL, but correlated positively with BCVA. CONCLUSIONS: Reduced CT in children with a history of ROP is linked to ROP severity. These findings overlap with the degree of MDA. CT appears to be involved in ROP, but MDA showed a higher impact on the BCVA of the examined cohort.

Structure-Function Correlation in Hemianopic Vision Loss in Children Aged 3-6 Years Using OCT and SVOP, and Comparison with Adult Eyes.

PURPOSE: To correlate visual field assessment with saccadic vector optokinetic perimetry (SVOP) in children with ganglion cell loss due to anterior pathway pathologies resulting in hemianopic visual field defects measured with optical coherence tomography (OCT). METHODS: 5 young (aged 3-6 years) and 5 adult patients with hemianopia, 10 healthy preschoolers (mean age 4.4 years), and 10 healthy adults (mean age 25.3 years) were tested with SVOP and OCT (focusing on the ganglion cell layer, GCL+). In adults, visual field testing was also performed with static and fundus-controlled perimetry. RESULTS: OCT allowed precise structure analysis and showed a vertical border with GCL+ loss on the hemianopic side in children and adults compared to controls. SVOP showed visual field defects on the hemianopic side in peripheral regions and inadequate results at the parafoveal positions in both groups. In contrast, static and fundus-controlled perimetry showed a clear border in foveal and parafoveal regions. CONCLUSIONS: All children underwent SVOP with minimal restrictions, allowing functional evaluation of peripheral visual field positions. Parafoveal positions showed multiple false-positive results. The function-structure relationship is measurable even in young children by using the GCL+ analysis. This combination of novel child-friendly techniques allows collecting objectively measured values and simplifies diagnosis and follow-up in treatment.

OCT Angiography in Young Children with a History of Retinopathy of Prematurity.

PURPOSE: To describe the size and appearance of the foveal avascular zone (FAZ) in the superficial and deep plexus in young children with treated or spontaneously regressed retinopathy of prematurity (ROP), in comparison with age-matched controls and young adults, as seen with OCT angiography (OCTA), and to compare these parameters with foveal classic OCT images and visual function. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Twenty-five children with treated or spontaneously regressed ROP (mean 5.0±0.8 years) compared with 15 healthy term-born age-matched children and 20 healthy adults. METHODS: OCTA was performed using a DRI OCT Triton (Swept Source OCT, Topcon, Oakland, NJ). The best-quality images of 1 eye per patient were analyzed. Superficial FAZ and deep FAZ were analyzed separately. Single-scan OCTs were performed using a Spectralis SD-OCT (HRA+OCT, Heidelberg Engineering, Heidelberg, Germany). The foveal pit characteristics and the degree of macular developmental arrest (MDA), defined as the ratio of the outer nuclear layer + external limiting membrane (ONL+) and the inner retinal layers in the fovea (ONL+/IRL-ratio), were analyzed with a custom-made automated layer segmentation tool (DiOCTA, copyright by Justus-Liebig-University, Giessen, Germany). Visual acuity (VA) was tested with Early Treatment of Diabetic Retinopathy Study letter charts. MAIN OUTCOME MEASURES: The ONL+/IRL-ratio, superficial FAZ area, deep FAZ area, foveal parameters, and VA. RESULTS: Foveal pit depth and area were significantly reduced in both treated and spontaneously regressed ROP, whereas the foveal diameter was comparable in all groups. OCTA showed a significantly narrowed superficial FAZ in eyes with treated and spontaneously regressed ROP. In contrast, the deep FAZ was of comparable size in all groups. A reduced superficial FAZ significantly correlated with reduced ONL+/IRL-ratio, and thus the degree of MDA. In treated and spontaneously regressed ROP, reduced superficial FAZ and MDA correlated significantly with diminished VA. CONCLUSIONS: OCTA is feasible in young children with a history of ROP and without neurodevelopmental delay. It allows detecting a decreased superficial FAZ size noninvasively. A small superficial FAZ, reduced ONL+/IRL-ratio as a measure of MDA, and reduced VA are concurrent factors in preterm children who are otherwise neurologically normal.

[The Impact of Macular Development on Full-field and Multifocal ERG in Extremely Preterm-born Children with and without Acute Retinopathy of Prematurity]. / Einfluss der Makulareifung auf Ganzfeld- und multifokales ERG bei ehemaligen Extremfrühgeborenen mit und ohne akute Frühgeborenenretinopathie.

Introduction Retinal development is a complex process that can continue into early childhood and beyond. Prematurity can affect the maturation of the central retina, characterised by a flatter foveal pit and overlying inner retinal layers (IRL), leading to a disturbed ratio of outer retinal layers to IRL ("macular developmental arrest": MDA) and functional impairment (Bowl et al. 2016 18). The purpose of this study was to correlate functional results by electrophysiology with the morphological appearance of the fovea in children with spontaneously regressed and without ROP and term-born age-matched controls. Methods We investigated n = 60 preterm-born children with spontaneously regressed (srROP, n = 15) and without ROP (noROP, n = 50) as part of an extensive prospective cohort study and compared them to n = 10 term-born age-matched controls (Term). Full-field electroretinogram (ffERG) and multifocal ERG (mfERG) based on ISCEV-standards were performed in every child for functional evaluation. Foveal morphology was evaluated with optical coherence tomography (SD-OCT, Spectralis, Heidelberg Engineering, Germany). Results Analysis of the scotopic ffERG showed significantly modified b-wave amplitudes in srROP and noROP, especially when MDA was found on SD-OCT. The mfERG exhibited a modified P1-component of the central hexagon and the second concentric ring in children with MDA. No other parameters were significantly changed. Conclusions Electrophysiological changes can be found in extremely preterm-born children, especially with OCT-confirmed foveal maturation impairment (MDA), namely in children with spontaneously regressed ROP as well as in children without ROP. The reduced b-wave in the scotopic ffERG and the reduced P1-component in the mfERG indicate involvement of bipolar cells in extremely prematurely born children with MDA. In particular, the correlation of MDA with ffERG could be a sign of more global retinal maturation disturbance accompanying MDA, and this is seen even without acute ROP.

OCT-Based Macular Structure-Function Correlation in Dependence on Birth Weight and Gestational Age-the Giessen Long-Term ROP Study.

PURPOSE: To compare retinal layer thicknesses in preterm and term-born children using spectral-domain optical coherence tomography (SD-OCT) and to correlate structure with retinal function. METHODS: We performed SD-OCT single and volume scans in the foveal region of premature children aged 6 to 13 years without ROP (no-ROP, n = 100) and with spontaneously regressed ROP (sr-ROP, n = 50) documented with wide-angle digital imaging during routine screening for acute ROP, and 30 age-matched term-born children. Retinal layer segmentation and analysis was performed with custom-made software in single and volume-scans using an Early Treatment of Diabetic Retinopathy Study grid-based method, and compared to light increment sensitivity (LIS) data obtained with a microperimeter at eccentricity points of 0°, 2.8°, and 8°, as previously described. RESULTS: Overall, seven children had to be excluded due to poor image quality (n = 1 no-ROP; n = 2 sr-ROP; n = 4 term). Total retina, ganglion cell + inner plexiform layer (GCL+) and outer nuclear layer + external limiting membrane (ONL+) thickness at the foveal center in no-ROP and sr-ROP were significantly higher compared with term children. Gestational age (GA) and birth weight (BW) were inversely correlated with these layer thicknesses. Rod and cone outer segment length did not differ in either group. The ratio of ONL+ to the whole retina at 0° correlated significantly with reduced LIS. CONCLUSIONS: Increased thicknesses of the entire retina or specific layers at the fovea did not correlate with functional loss; but a thinner ONL in retinae without foveal pit did. This reduced ONL+ ratio is potentially caused by a reduced foveal cone density and may be the first morphologic functional correlate in prematurity and ROP.

Fundus-controlled two-color dark adaptometry with the Microperimeter MP1.

PURPOSE: The aim of this study was to provide fundus-controlled two-color adaptometry with an existing device. A quick and easy approach extends the application possibilities of a commercial fundus-controlled perimeter. METHODS: An external filter holder was placed in front the objective lens of the MP1 (Nidek, Italy) and fitted with filters to modify background, stimulus intensity, and color. Prior to dark adaptometry, the subject's visual sensitivity profile was measured for red and blue stimuli to determine whether rods or cones or both mediated the absolute threshold. After light adaptation, 20 healthy subjects were investigated with a pattern covering six spots at the posterior pole of the retina up to 45 min of dark adaptation. Thresholds were determined using a 200 ms red Goldmann IV and a blue Goldmann II stimulus. RESULTS: The pre-test sensitivity showed a typical distribution of values along the meridian, with high peripheral light increment sensitivity (LIS) and low central LIS for rods and the reverse for cones. After bleach, threshold recovery had a classic biphasic shape. The absolute threshold was reached after approximately 10 min for the red and 15 min for the blue stimulus. CONCLUSIONS: Two-color fundus-controlled adaptometry with a commercial MP1 without internal changes to the device provides a quick and easy examination of rod and cone function during dark adaptation at defined retinal loci of the posterior pole. This innovative method will be helpful to measure rod vs. cone function at known loci of the posterior pole in early stages of retinal degenerations.

Optical Coherence Tomography (OCT) Device Independent Intraretinal Layer Segmentation.

PURPOSE: To develop and test an algorithm to segment intraretinal layers irrespectively of the actual Optical Coherence Tomography (OCT) device used. METHODS: The developed algorithm is based on the graph theory optimization. The algorithm's performance was evaluated against that of three expert graders for unsigned boundary position difference and thickness measurement of a retinal layer group in 50 and 41 B-scans, respectively. Reproducibility of the algorithm was tested in 30 C-scans of 10 healthy subjects each with the Spectralis and the Stratus OCT. Comparability between different devices was evaluated in 84 C-scans (volume or radial scans) obtained from 21 healthy subjects, two scans per subject with the Spectralis OCT, and one scan per subject each with the Stratus OCT and the RTVue-100 OCT. Each C-scan was segmented and the mean thickness for each retinal layer in sections of the early treatment of diabetic retinopathy study (ETDRS) grid was measured. RESULTS: The algorithm was able to segment up to 11 intraretinal layers. Measurements with the algorithm were within the 95% confidence interval of a single grader and the difference was smaller than the interindividual difference between the expert graders themselves. The cross-device examination of ETDRS-grid related layer thicknesses highly agreed between the three OCT devices. The algorithm correctly segmented a C-scan of a patient with X-linked retinitis pigmentosa. CONCLUSIONS: The segmentation software provides device-independent, reliable, and reproducible analysis of intraretinal layers, similar to what is obtained from expert graders. TRANSLATIONAL RELEVANCE: Potential application of the software includes routine clinical practice and multicenter clinical trials.

Improving detection of mild loss of retinal light increment sensitivity at the posterior pole with the microperimeter MP1.

PURPOSE: With "standard" stimuli (white, Goldmann size III, 200 ms), the Nidek Microperimeter MP1 underestimates retinal light increment sensitivity (LIS). We thoroughly analyze this problem, suggest alternative settings to improve sensitivity to detect dysfunction, and provide true normal values. METHODS: LIS was tested at 55 positions in the macular region using a 4-2-1 staircase strategy with 200 ms white or red stimuli on a 1.3 cd m⁻² background. Stimulus size was Goldmann III and I, and additionally II in the healthy subjects. All participants underwent a complete ophthalmologic examination, spectral domain optical coherence tomography (OCT), and fundus autofluorescence (FAF). RESULTS: In normals, distributions of LIS for white Goldmann sizes II and III within the central 6° to 10° were clipped off at 20 dB--the MP1 cannot attenuate them any further. When the stimulus size was reduced to Goldmann I or the color changed to red, median LIS in the fovea (∼15 dB) was approximately 5 dB higher than at 10° eccentricity. Estimated from these results, central LIS for white Goldmann sizes II and III stimuli were 21 and 27 dB, respectively. In four patients with either focal or diffuse macular pathology, as confirmed by funduscopy, OCT, or FAF, reduced LIS was detected clearly with Goldmann size I stimuli, but not III. CONCLUSIONS: In all subjects reported here, standard central LIS was above the technical limit of the MP1. To measure true thresholds in healthy subjects, either smaller (Goldmann size I) or dimmer stimuli (red) must be used.