Silent sicklers and traumatic hyphema: the importance of maintaining a high index of suspicion

Summary

A previously healthy 6-year-old white boy presented emergently after trauma to his right eye. On examination, intraocular pressure (IOP) was 49 mm Hg, and visual acuity was 20/50. He was diagnosed with a 3 mm layering hyphema. Despite medical therapy and lifestyle modifications, the patient’s IOP continued to rise, peaking at 77 mm Hg on day 3 after presentation. Given his elevated IOP despite the addition of new topical medications on daily follow-up, the patient was screened for sickle-cell disease to assess for an underlying pathology that could be exacerbating his elevated IOP. After testing positive for sickle cell trait, the patient was promptly taken to the operating room for anterior chamber washout. The following day, IOP normalized to 14 mm Hg, and visual acuity was 20/25. Hyphemas generally respond well to medical therapy, but patients with sickle cell hemoglobinopathy are at greater risk for permanent vision loss from pressure spikes. This case reinforces the need to collect thorough past medical and family histories and consider early sickle cell screening in all patients failing to respond to IOP-reducing medication or if hemoglobin status is unknown on initial presentation.

Introduction

The accumulation of erythrocytes in the anterior chamber (AC), known as hyphema, can have many etiologies. Hyphemas most commonly result from blunt trauma due to disruption of normal ocular anatomy and exposure of AC vasculature to shearing forces, resulting in hemorrhage.1 Sickle cell trait (SCT), an entity on the spectrum of sickle cell hemoglobinopathies associated with the inheritance of one normal hemoglobin A gene and one abnormal hemoglobin S (HbS) gene, is a known disease state that complicates hyphema management.2,3 Although many patients with SCT are asymptomatic, erythrocytes composed of any HbS are susceptible to sickling under certain physiologic contexts, which can have significant negative consequences on vital tissues, particularly the eyes.2 Traumatic hyphemas complicated by SCT have a propensity for intraocular pressure (IOP) spikes due to obstruction of aqueous humor flow through the trabecular outflow tract, resulting in intraocular hypoperfusion and subsequent hypoxia, which further perpetuates a cycle of sickling and tissue damage.3

Physicians must be aware of a patient’s hemoglobin status to properly mitigate the risk of ocular sequelae in patients with a traumatic hyphema. Although the exact prevalence of SCT is unknown, the Center for Disease Control and Prevention (CDC) and the National Institutes of Health estimate that over 2 million people in the United States (US) have SCT, with approximately 1 in 13 black babies affected.4 A 2010 CDC report noted incidence rates of 73.1 per 1,000 black newborns, 3.0 per 1000 white newborns, 2.2 per 1000 Asian or Pacific Islander newborns, and 6.9 per 1000 Hispanic newborns across 13 states.5 Other reports suggest that SCT prevalence is around 9% in blacks and 0.2% in whites, with rates potentially rising due to migration from regions with higher SCT.6 Given the relatively low prevalence of SCTs in non-black populations, failure to consider its presence can result in marked consequences. We present a rare case of traumatic hyphema complicated by SCT in a white 6-year-old boy and review the existing literature relevant to traumatic hyphema management in the setting of SCT.

Case Report

A 6-year-old boy with no known past medical history presented emergently at Prisma Health Hospital with right eye pain, photophobia, and blurry vision following blunt trauma with a foam projectile (Figure 1). On initial examination, the patient’s uncorrected near visual acuity was 20/50 in his right eye and 20/20 in the left eye, with IOP of 49 mm Hg and 14 mm Hg by Tono-Pen (Reichert Technologies, Depew, NY; https://www.reichert.com/), respectively. Following administration of topical timolol, right eye IOP fell to 20 mm Hg. The patient’s pupils were round, equal, and reactive in both eyes without evidence of an afferent pupillary defect, and no deficits were found with motility, confrontation visual fields, or color vision testing. On slit-lamp examination, the patient was found to have 1+ injection, with an inferior 3 mm layered hyphema with suspended erythrocytes and AC flare in the right eye. Fundus examination of the right eye was difficult to assess, given the AC reaction; however, ultrasound demonstrated an intact posterior segment, without retinal detachment or vitreous hemorrhage. The patient was started on timolol maleate 0.5%, prednisolone acetate 1%, and tropicamide 1%, counseled to sleep in a semirecumbent position and avoid strenuous activity, and given instructions for follow-up. Of note, cyclopentolate 1% and atropine 1% topical drops were unavailable at this time, necessitating the use of tropicamide for cycloplegia.

Figure 1.

External photograph showing a 3 mm layered hyphema in the right eye on initial presentation.

Through follow-up days 1 and 2, the patient’s examination was stable, but his IOP remained elevated at and above 37 mm Hg while on topical timolol. Topical dorzolamide HCL 2% and brimonidine tartrate 0.2% were then added to achieve better IOP control. During the follow-up visits, the patient’s family reported diligent adherence to the prescribed regimen, strict upright bed rest, and abstinence from nonsteroidal anti-inflammatory medications. Despite these efforts, the patient presented on follow-up day 3 with significant worsening in eye pain, an uncorrected visual acuity of 20/150, IOP of 76 mm Hg and 77 mm Hg on sequential measurements (Tono-Pen), 2 mm inferior clotted hyphema, and new-onset corneal edema, with no signs of rebleeding on right eye examination. Gonioscopy was attempted; however, angle examination was unsuccessful because of patient discomfort. Upon further questioning of the patient’s family, the mother did report a history of SCT in the child’s maternal uncle. Given the patient’s worsening IOP on three topical pressure-lowering agents, the decision was made to screen the patient for sickle cell disease (SCD) and pursue an urgent AC washout to mitigate the risk of corneal blood staining and optic nerve damage.

On postoperative day 1, his visual acuity was 20/25⁻¹, with an IOP of 14 mm Hg in the right eye off topical pressure therapy with normal slit-lamp examination. IOP remained 14 mm Hg in the right eye. Dilated fundus examination revealed sharp optic nerve disc margins without focal thinning or hemorrhage, a 0.4 cup-to-disc ratio, and normal-appearing fundus on postoperative month 1 follow-up without asymmetry relative to left eye examination. Because patient participation was limited, optical coherence tomography of the optic nerves could not be performed. In the days following his procedure, the patient’s hemoglobin electrophoresis demonstrated a hemoglobin S proportion of 38.8%, hemoglobin A2 proportion of 3.2%, and hemoglobin A proportion of 58.0%, consistent with the diagnosis of SCT. Of note, his newborn screen obtained from outside records retrospectively was significant for the presence of fetal, adult, and sickle hemoglobin; however, it was qualified as “no variant detected” and was not mentioned in further obtainable clinical documentation.

Discussion

SCT is a relatively silent pathologic state due to its asymptomatic nature, and most individuals with SCT do not experience any complications associated with the phenotype.2 This is a necessary component of the disease to consider, because only 16% of patients of childbearing age with SCT are familiar with their SCT status.2 While it is mandated that newborns be screened for SCT in the United States, patient data pertaining to their SCT status has the potential to be lost in the transfer from paper medical records to electronic medical records, as in the case of our patient, or forgotten with age in the absence of symptoms. This information is critical from the ophthalmologist’s perspective to tailor patient management appropriately in the setting of traumatic hyphema, because patients with SCT are at increased risk of secondary hemorrhage, increased IOP, and permanent vision loss via subsequent optic atrophy.3,7,8

Polymerization of HbS and the resultant change in erythrocyte morphology are the pathophysiological hallmarks of sickle cell hemoglobinopathies that initiate vaso-occlusion and tissue damage. Although patients with SCT rarely experience sickle cell crises, erythrocytes with any proportion of HbS have the potential for sickling in the presence of severe hypoxia, dehydration, acidosis, infection, and increased sympathetic outflow.2 In the context of a hyphema, erythrocytes composed of HbS are likely to sickle in the relatively hypoxic aqueous humor promoting mechanical obstruction within the trabecular meshwork (TM) and subsequent IOP elevations.9,10 Laboratory studies conducted by Goldberg et al11 demonstrated that sickled erythrocytes reduce aqueous pH and the partial pressure of oxygen when injected into the anterior chamber of rabbits, potentiating further propagation of TM obstruction in the setting of anterior segment bleeding.

The susceptibility of SCT patients to sickling in the presence of IOP-lowering therapies further exacerbates the severity of the issue by reducing the arsenal of available options, because carbonic anhydrase inhibitors (CAIs) and osmotic agents, such as mannitol and glycerol, are contraindicated, given their theoretical propensity to reduce aqueous pH and cause dehydration, respectively.1,9,12 Topical therapy is limited to beta-blockers (eg, timolol or levobunolol) with cautious use of alpha-agonists and prostaglandins due to effects on iris vasculature and the promotion of inflammation.13 Given limitations in therapy, daily follow-up examinations for hyphema improvement or progression and IOP checks are critical to assess the need for surgical intervention to prevent optic nerve damage and corneal blood staining. It is important to recognize the paucity of evidence pertaining to medication efficacy or the acute effects of ocular hypertension in this patient population to make specific protocols for sickle cell disease/trait (SCT/D) hyphema management; physicians should use their best judgment regarding medical and surgical care on a case-by-case basis.14 Current indications for surgical evacuation of hyphema include the following:

1. Corneal blood staining

2. Significant visual deterioration

3. Failure of hyphema to decrease in size by ≤50% by 8 days

4. IOP ≥60 mm Hg ≥48 hours despite maximal medical therapy

5. IOP ≥25 mm Hg with total hyphema for ≥5 days

6. IOP ≥24 mm Hg for ≥24 hours (or any transient increase in IOP ≥30 mm Hg) in sickle cell trait or disease patients.13

At present, there are no specific guidelines on SCD/T screening as part of a hyphema workup. Recent literature recommends screening all black patients presenting with hyphema or microhyphema for SCD and further suggests a low threshold to screen patients of Mediterranean and Indian descent.8,12,15 Although the prevalence is low in non-African descendant populations, it is not zero. Our white patient maintained an IOP greater than the recommended pressure threshold for 72 hours before the decision to pursue surgical intervention was made because of delayed consideration of hemoglobinopathy assessment.13 Fortunately, no adverse outcomes associated with his persistently elevated IOP have been observed on follow-up examinations. Additionally, although the concerns about topical CAI use in SCD/T patients appear theoretical and unproven, we observed a marked increase in our patient’s IOP after starting dorzolamide.12 Had we known about his SCT, we likely would have withheld the dorzolamide and kept a lower threshold to pursue surgery, given his clear indication of SCT and IOP ≥24 mm Hg for ≥24 hours—the “24 for 24” rule.12,13,16 However, it is difficult to discern whether these agents directly contributed to his worsening IOP or their ineffectiveness was due to the exacerbation of mechanical obstruction by way of sickled cells in the AC promoting further sickling.

Despite the prevalence discrepancies among various races, the presence of SCD/T significantly influences the management of hyphemas to mitigate the risk of long-term ocular morbidity.10,12 Given the asymptomatic nature of SCT and the low incidence of patient familiarity with their SCT status, patients without a documented or known history of their hemoglobin status should be considered for hemoglobinopathy screening at the time of initial presentation. Screening for SCD/T through hemoglobin solubility testing and/or electrophoresis is relatively cheap, and with a turnaround time for results ranging from 24 hours to 4 days, depending on lab and institution capabilities, screening at initial presentation may allow for the most timely and tailored management.17,18

In summary, we present a rare case of SCT in a white child with a traumatic hyphema. This case underscores the significance of collecting thorough past medical and family histories during the initial patient evaluation for hyphema. Without specific screening guidelines, we recommend the consideration of early screening for sickle cell hemoglobinopathy for all patients with a hyphema failing to respond to topical therapy or those with unknown hemoglobin status at the time of initial presentation.