Purpose-To determine whether recovery of scotopic sensitivity occurs in human ROP, as it does in rat models of ROP.Methods-Following a cross-sectional design, scotopic electroretinographic (ERG) responses to full-field stimuli were recorded from 85 subjects with a history of preterm birth. In 39 of these subjects, dark adapted visual threshold was also measured. Subjects were tested post term as infants (median age 2.5 months) or at older ages (median age 10.5 years) and stratified by severity of ROP: severe, mild, or none. Rod photoreceptor sensitivity, S ROD , was derived from the a-wave and post-receptor sensitivity, log σ, was calculated from the b-wave stimulus-response function. Dark adapted visual threshold was measured using a forced-choice preferential procedure.Results-For S ROD , the deficit from normal for age varied significantly with ROP severity but not with age group. For log σ, in mild ROP, the deficit was smaller in older subjects than in infants, while in severe ROP, the deficit was quite large in both age groups. In subjects who never had ROP, S ROD and log σ in both age groups were similar to those in term born controls. Deficits in dark adapted threshold and log σ were correlated in mild but not in severe ROP.Conclusions-The data are evidence that sensitivity of the post-receptor retina improves in those with a history of mild ROP. We speculate that beneficial reorganization of the post-receptor neural circuitry occurs in mild but not in severe ROP. Keywordsretinopathy of prematurity; neural retina; electroretinogram; rod photoreceptor; dark adapted visual threshold Retinopathy of prematurity (ROP), even if mild, causes long term deficits in rod and roddriven post-receptor retinal function that persist long after acute phase ROP has resolved. Compared to term born controls, in the majority of ROP subjects, both rod photoreceptor and post-receptor response parameters are below average from early infancy into adulthood; former preterms who never had ROP do not differ from age-similar controls [1]. Rod and post-receptor retinal dysfunction are also noted in rat models of ROP [2][3][4][5][6][7][8][9]. In rats followed longitudinally, postreceptor sensitivity recovers whereas photoreceptor sensitivity remains abnormal [2].To determine if there is evidence of recovery of sensitivity in human ROP, we reviewed rod photoreceptor and post-receptor ERG parameters in infants and older subjects with a history of preterm birth. Dark adapted visual thresholds were also evaluated for significant relationship to ERG indices of sensitivity. The effects of age and ROP severity on these cross-sectional ERG and threshold data from infant and older subjects were analyzed. METHODS SubjectsRod and rod-driven ERG parameters from 85 subjects with a history of preterm birth were analyzed (Table 1A). Peripheral dark adapted visual thresholds obtained from 39 of these subjects were also analyzed (Table 1B). ERG parameters from 68 of the subjects [1] and threshold data from 11 [10] have been reported previously....

A broad spectrum of retinal diseases affects both the retinal vasculature and the neural retina, including photoreceptor and postreceptor layers. The accepted clinical hallmarks of acute retinopathy of prematurity (ROP) are dilation and tortuosity of the retinal vasculature. Additionally, significant early and persistent effects on photoreceptor and postreceptor neural structures and function are demonstrated in ROP. In this paper, we focus on the results of longitudinal studies of electroretinographic (ERG) and vascular features in rats with induced retinopathies that model the gamut of human ROP, mild to severe. Two potential targets for pharmaceutical interventions emerge from the observations. The first target is immature photoreceptors because the status of the photoreceptors at an early age predicts later vascular outcome; this approach is appealing as it holds promise to prevent ROP. The second target is the interplay of the neural and vascular retinal networks, which develop cooperatively. Beneficial pharmaceutical interventions may be measured in improved visual outcome as well as lessening of the vascular abnormalities.As a system, the mammalian retina is vulnerable to diseases that affect the exquisitely balanced interplay of the neural retina and the vasculature that nourishes it. Visual loss occurs when this balance is disturbed. On the one hand, diseases such as photoreceptor degenerations that primarily affect the neural retina also affect the retinal vasculature. On the other hand, diseases that are clinically characterized by abnormality in the choroidal or retinal vasculature, such as age related macular degeneration, diabetic retinopathy, and retinopathy of prematurity (ROP), also affect the retinal neurons. Thus, all such diseases fall within the broad group of hypoxic ischemic disorders of neural tissue. Photoreceptors, specialized cells that have the highest oxygen requirements of any cell in the body [1], are likely important in all hypoxic ischemic diseases of the retina. Translation from animal models to patientsThe photoreceptors are nestled closely to the choroidal vasculature (figure 1). Highly organized postreceptor retinal neurons form layers that are supplied by the retinal vessels. Although the choroid is the principal supply to the photoreceptors, degeneration of the photoreceptors is, nonetheless, associated with attenuation of the retinal arterioles [2]. Because the photoreceptor layer is such an extraordinary oxygen sink, it is presumed that, as photoreceptors degenerate, their metabolic demands wane and the retinal vasculature becomes attenuated consequent to the neural retina's chronic lower requirement for oxygen [2]. NIH-PA Author ManuscriptA tight link between the photoreceptors and the retinal vascular network is evident in the developing retina. Postreceptor cells differentiate before the photoreceptors, which are the last retinal cells to mature. As the formation of rod outer segments advances in a posterior to peripheral gradient, so too does vascular coverag...

It is known that retinopathy of prematurity (ROP) alters the activation of rod photoreceptors, but the effect of ROP on deactivation has not been investigated. We studied deactivation using a paired flash procedure in 22 subjects (12 infants and 10 older subjects) with a history of preterm birth and ROP. The amplitude of the rod isolated a-wave response to a flash presented 2 to 120 seconds after a test flash was measured, and the time at which it reached 50% of the single flash amplitude (t 50 ) was determined by linear interpolation. Deactivation results were compared to those in former pre-terms who never had ROP (n=6) and term born controls. In infants, t 50 values of ROP subjects did not differ from those in subjects who never had ROP or term born controls. Among mature ROP subjects, eight of 12 had t 50 values longer than any control subject. Prolonged deactivation in these mature ROP subjects may indicate lack of maturation of the deactivation process (t 50 ) or progressive compromise of retinal function with increasing age.