For better differentiation between patterns of ocular hemorrhage from accidental and AHT in children, it is important to understand the mechanisms and loading conditions that can cause these injuries. We sought to evaluate an immature animal model for its potential to study mechanisms of traumatic hemorrhage associated with head accelerations. We found that approximately three-fourths of the animals in this preliminary model developed ocular hemorrhage as the result of a single, high-velocity head rotation, even though the limited number of histologic cuts may have led to an underestimation of findings. Seventy percent of hemorrhages were located in a region of strong vitreoretinal attachment in the pig. Thus, this animal model will be useful for evaluating the role of the vitreoretinal interface in the development of hemorrhage from rotational head accelerations. However, to assess the clinical relevance of this model, one must consider the pattern and severity of ocular injuries, the similarities and differences between pig and human ocular and orbital anatomy, and the nature and magnitude of the loads applied.
Retinal hemorrhages have been reported to occur in 0% to 20% of cases of pediatric accidental head trauma, depending on the cause of injury. The higher reported incidences are from case series investigating crush head injuries or fatal motor vehicle accidents. When present, the retinal hemorrhages in young children with accidental head trauma are typically intraretinal, few in number, and confined to the posterior pole, even in complex falls with multiple impacts.12–16
Rarely, in cases of severe trauma, such as fatal motor vehicle accidents or crush head injuries, more extensive hemorrhages can be seen.17
In contrast, retinal hemorrhages in children with AHT can range from a few, isolated intraretinal hemorrhages, as seen in accidental trauma, to numerous hemorrhages that may be multilayered and extend into and throughout the retinal periphery and can include macular folds and hemorrhagic macular cysts.18–22
The distribution and types of hemorrhages reported in abusive and accidental head trauma may be informative with regard to mechanistic etiology. The overlap in findings at the mild end of the injury spectrum and occasionally at the severe end of the injury spectrum (e.g., fatal car accidents) suggests that there may be some common mechanism(s) underlying the retinal hemorrhages in accidental and AHT. However, the additional patterns of injury in AHT (e.g., macular cysts) suggest that additional mechanisms may be involved in those cases.
A favored theory in the literature is that acceleration–deceleration forces cause the vitreous to pull on the retina, possibly damaging retinal vessels, with subsequent hemorrhaging, or causing changes in vascular autoregulation.23
In our study, most of the intraocular hemorrhages were located near the vitreous base in the form of ciliary body hemorrhage or less frequently as peripheral retinal hemorrhage. It is not clear how this pattern of injury relates clinically to pediatric head trauma, as the vitreous base is not typically visualized on clinical examination in the awake child without scleral depression, and ophthalmologists are unlikely to perform scleral depression in awake children in the absence of posterior pole findings. However, the location of the hemorrhages is coincident with areas of strong vitreoretinal attachment in the pig,24
suggesting a possible role for traction in the model. In fact, ciliary body and optic nerve sheath hemorrhages have been described on postmortem examination in AHT.20,21
Another mechanistic theory involves the direct tracking of blood from the brain along the optic nerve and into the eye. Most of the animals in our study had an optic nerve sheath subdural hemorrhage and a few animals had microscopic optic disc hemorrhages. However, the nerve sheath hemorrhages were focal rather than spread over the length of the nerve, and no retinal hemorrhage was observed posteriorly in the eye; on the contrary, most of the intraocular hemorrhages were found anteriorly.
A third theory involves increased intracranial or intravenous pressure. The pattern of ocular hemorrhage observed in this preliminary model matches neither the peripapillary hemorrhages associated with papilledema nor the distinctive retinal hemorrhage pattern of retinal venous occlusion, but we did not measure intracranial or intravenous pressure in this study.
We selected the immature piglet as a potential model for the study of retinal hemorrhages, as the porcine retina is more similar to the human retina than other domestic animals.25,26
Specifically, the porcine retina does not have a tapetum and contains a well-developed vascular arcade, with the major retinal vessels lying within the nerve fiber layer and capillaries present throughout multiple layers of the retina. The vitreous base of the pig is comparable to the human vitreous base and straddles the ora. However, the piglet eye does not contain a fovea or a macula, and there is debate in the literature over whether it has a macula-like region devoid of major retinal vessels.25,26
We found one persistent hyaloid vessel hemorrhage in our study, but piglet hyaloid vessels typically regress before birth, with hyaloid remnants persisting for 1 week after birth.27
Since completion of this study, we have examined the eyes of several additional 3- to 5-day-old piglets and noted many with clear hyaloid stalks, but none with hyaloid arteries containing blood.
Vitreoretinal attachments in the pig have been reported to occur throughout the retina, but one plasmin-assisted vitrectomy study demonstrated that the attachments at the vitreous base are stronger compared to other regions.24
In humans, vitreoretinal attachments occur across the entire retina, as they do in the pig, but locations of stronger attachment are at the vitreous base, optic nerve head, macula, and along major retinal vessels.28,29
Should vitreoretinal traction play a significant role in the development of retinal hemorrhages, these ocular anatomic differences may influence the patterns of hemorrhage seen experimentally.
Contrasts in human and porcine orbital anatomy may also affect the patterns of observed injury. The pig has an open orbit, and instead of a bony closure, a strong fibrous ligament stretches from the frontal bone to the zygomatic bone, effectively enclosing the orbit but with slightly less rigidity than in humans.25
Although this relative laxity may allow more freedom of movement for the orbital contents, the pig's extraocular muscles may inhibit the globe's motion. The annulus of Zinn is absent, and the origins of the muscles are on bone and are characterized as extremely strong.25
In addition, the pig, like most domestic animals, has an additional muscle called the retractor bulbi, which inserts circumferentially on the globe and retracts it into the orbit, allowing the nictitating membrane, or third eyelid, of the animal to close and further inhibit movement of the globe within the orbit.25
Future studies are necessary to evaluate whether movement within the orbit is an important factor in the pathogenesis of ocular hemorrhage in pediatric head trauma.
A final anatomic consideration is the orientation of the porcine eye. We observed that animals with axial head rotations appeared to have more ocular hemorrhages than did animals with sagittal or coronal rotations, although the differences were not statistically significant. The visual axis of the pig is oriented approximately 30° outward from that of the human. This 30° offset causes a 50% decrease in the force being applied along the optic nerve during sagittal head rotation and an 87% increase in the force along the optic nerve during coronal head rotation. The offset would not cause any difference in the forces applied to the eye during axial head rotation. Assuming that there is a relationship between the inertial load applied along the optic nerve and the development of ocular hemorrhage, these calculations suggest that for a given load, our porcine animal studies may underestimate the incidence of ocular hemorrhage from sagittal rotations and overestimate the incidence from coronal rotations in comparison with that expected in a human.
It is important to recognize that the load applied in this study was a single, high-velocity rotation of the head and not a low-velocity, repetitive, back-and-forth motion often reported in cases of AHT. We selected a single, high-velocity head rotation to establish the ability of the model to produce ocular hemorrhages from angular head acceleration and to serve as a baseline for future studies investigating the effect of cyclic back-and-forth head rotations on eye injury. To date, the only controlled animal experiment investigating retinal hemorrhages from repetitive, cyclic head rotations has been in mice.30
The mouse eye is extremely small in mass compared with the human infant eye, and to achieve an equivalent scaled load, a shaking frequency five times greater than that found physically possible in investigations of loads from shaking infant surrogate dolls (2–3 Hz) is necessary.31
Investigations of cyclic loading that can better approximate real-world forces and are more similar to human retinal and vasculature structure would be of greater value in a large animal model such as the pig.
The single, high-velocity head rotations applied in this animal model were of sufficient magnitude to result in severe brain injury in almost all the animals. When scaled to the brain mass of a human infant (420 g), the applied head rotations are greater than those measured for low-height falls (1–2 feet) onto concrete,32
but less than would occur during an inflicted impact onto a hard surface.31,33
Because the mass of the immature porcine eye is similar to the mass of the human infant eye (2.29 g),34
scaling is less important. The axial length of the piglet eye measured postmortem is smaller (14 mm) than the axial length measured in vivo in the human infant (17 mm).35
Postmortem shrinkage may account for some shortening, but it is unclear whether the remaining difference is primarily attributable to vitreous chamber size or anterior chamber depth or how changes in axial length may affect ocular hemorrhage from rapid, nonimpact rotations of the head. Clinical conclusions regarding ocular injuries cannot be made from these animal studies until we know how anatomic differences between the human and porcine orbit affect the way mechanical loads applied to the head are translated to mechanical loads experienced by the eye.
To date, there is no experimental model that can be used to investigate the mechanisms and loading conditions that cause retinal hemorrhages in pediatric head injuries. The development of such a model may have important clinical, legal, and social implications related to accurately identifying and protecting children who are suffering child abuse, while correctly differentiating accidental injuries. We investigated the potential of the neonatal piglet as such a model. Optic nerve sheath and ciliary body hemorrhages were common in piglets that experienced a single, nonimpact head rotation, with some retinal hemorrhage, which was less common but all of which was located near the ciliary body at the vitreous base. Although this pattern differs from the severe, diffuse retinal hemorrhages often seen in cases of AHT, we are encouraged by the high percentage of animals demonstrating a rather consistent pattern of ocular injuries, the localization of injuries to regions of strong vitreoretinal attachment in the pig, and the common finding of optic sheath nerve hemorrhages. Future studies will include evaluation of lower velocity cyclic loading conditions and manipulations of the vitreoretinal interface and extraocular muscle anatomy. Anatomic differences between the species may affect the observed injury patterns in the model, and such differences must be investigated before experimental results can be safely extrapolated to head injuries in infants.