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

Abstract

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.

Keywords: dark adaptometry; macular developmental arrest MDA; optical coherence tomography; prematurity; retinopathy of prematurity.

Figure 1

Schematic of the stimuli presented in this study. (A) Stimuli were presented at six positions of a customized pattern on the posterior pole of the retina. Three temporal blue (at 12°) and three central red stimuli (within 2°) on a background of 0.16 cd/m² were used in each measurement set, respectively (Goldmann III size stimuli). (B) One sequence with three stimuli lasted for 30 to 45 seconds and was repeated every 2 minutes during the whole session.

Figure 2

The composition of the preterm-born children groups participating in our study according to ROP in medical history and foveal morphology, as seen with OCT. Macular developmental arrest MDA was defined, in accordance with the study of Bowl et al., when the ratio between the ONL+ELM and inner retinal layers (ONL+/IRL) was ≤6.5. Bottom line: two examples of MDA (left OCT scan) and foveal insemination (right OCTimage). Of note, phenotypic variability concerning the foveal insemination in MDA is high.

Figure 3

Distribution of visual acuity data among all probands of this study, depending on the presence of MDA and highest stage of acute ROP, and in comparison with age-similar healthy controls. Status bars: Mean values in each group.

Figure 4

Dark adaptation course measured with a modified fundus-controlled Microperimeter MP1 (Nidek Technology) in preterm-born children with spontaneously regressed or without retinopathy of prematurity divided into the groups normal foveal morphology (no-MDA, n = 47; [A]) or macular developmental arrest (MDA, n = 43; [B]). In each case, the cone-mediated sensitivity (red filled area) to red stimuli and rod-mediated sensitivity (blue filled area) are shown. Dark adaptation dynamic fit curve (polynomial 4. order) is shown with 0.95 confidence interval (dotted lines) and prediction interval (continuous outer lines).

Figure 5

(A) The dark adaptation curves of exemplary measurements for a preterm-born child with MDA and for a preterm and a term-born child with regular foveal morphology (no-MDA). Lines mark each of the linear regression curves for each subject. Description of symbols and colors is given at the bottom of the Figure. (B) Overall linear gradient of the rapid phase of the dark adaptation course of all participating children.