Neuroimaging of ocular involvement in patients with sickle cell disease and review of the literature

Abstract

Endophthalmitis is a rare cause of ocular infection that can be associated with immunocompromising conditions and, more rarely, with sickle cell disease. In this case report and review of the literature, we present a case of a young male with sickle cell disease who presented with rapidly progressive ocular pain, edema, erythema, and decreased visual acuity. The key radiological findings to suggest endophthalmitis were demonstrated using computed tomography and magnetic resonance imaging.

Introduction

Endophthalmitis is generally caused by intraocular colonization with bacteria, fungi, or parasites.¹ Immunocompromising diseases and intravenous drug use are associated risk factor for endophthalmitis. Bilateral presentation is observed in approximately 14–25% of the patients. The majority of the patients are initially misdiagnosed clinically as having other ocular diseases (such as anterior uveitis and cellulitis). We present a case of bilateral endophthalmitis in a patient with sickle cell disease.

Case report

A 28-year-old male with sickle cell disease and chronic use of marihuana presented to the emergency room with one week history of progressive bilateral pain ocular, erythema, and proptosis. There was no definite visual field deficit.

The initial computed tomography (CT) scan (Figure 1(a) of the orbits performed without contrast was within normal limits. Blood cultures and chest X-ray were negative.

Figure 1.

CT scan assessment (512 × 512 × 16, kV: 120.00, mA: 240, tilt: 0, slice: 5 mm). (a) CT scan without contrast on day 1: orbits within normal limits. (b) CT scan with contrast, 1 week later: bilateral pre-septal soft tissues edema (arrows), diffusely enhancing sclera (black stars). (c) CT scan without contrast six months later: resolution of the pre-septal edema, phthisis bulbi (black stars).

The follow-up CT scan and magnetic resonance imaging (MRI) performed one week later showed pre-septal soft tissue edema and a diffusely thickened and enhancing sclera. The MRI (Figure 2) also showed restricted diffusion within the eye globe.

Figure 2.

MRI assessment, acute phase. (a, b) Pre-contrast T1-WI (TR: 486, TE: 15, slice: 5.5 mm), fat-suppressed T2-WI (TR: 3590, TE: 98, slice: 5.5 mm): heterogeneous signal intensity within the ocular globes representing infectious material (black stars). (c, d) Post-contrast T1-WI (TR: 400, TE: 17, slice: 5.5 mm) and FLAIR (TR: 9,000, TE: 94, TI: 2,500, slice: 5.5 mm): pre-septal soft tissue edema with diffuse enhancement (arrows), heterogeneous enhancement of the inflammatory material within the ocular globes. (e, f) DWI, ADC (b1000, TR: 3,400, TE: 81, slice: 5.5 mm): restricted diffusion within the ocular globes (black stars).

Following treatment, the MRI demonstrated significant shrinking and irregular appearance of the eye globes, and multiple vitreal septations, with resolution of the restricted diffusion changes. The clinical outcome was bilateral blindness.

Discussion

Endophthalmitis

Endophthalmitis is defined as inflammation of the vitreous chamber. The clinical presentation of endophthalmitis includes blurry vision, red eyes, pain, decreased visual acuity, conjunctival injection, hypopyon, corneal edema, and vitritis.^2,3

It is classified into exogenous and endogenous subtypes. The exogenous presentation is related to trauma or surgery, and rarely related to cataract surgery (0.01–0.3%).⁴ The endogenous endophthalmitis is caused by hematogenous spread of a systemic infection with crossing of the blood through the retina barrier resulting in ocular involvement. Although rare and representing only 2–8% of all cases of endophthalmitis, the endogenous subtype of endophthalmitis is the most prevalent type in patients with immunosuppression.^2,5,6

Even though there is no gender predisposition, different studies showed a higher prevalence in men (65%).^7,8 Diabetes is the most frequent associated comorbidity; other frequent risk factors are gastrointestinal disorders, systemic hypertension, heart valve disease, meningitis, splenectomy, and, rarely, hemoglobin SC. In the systematic review by Timonthy et al. of 342 patients, 33% were diabetic patients, 5% were intravenous drug users, 3% showed HIV infection, 3% had underlying malignancy, and 3% had autoimmune diseases.²⁵

The prognosis of endophthalmitis is poor and it usually leads to complete or significant visual loss.

Ocular manifestations of sickle cell disease

Patients with sickle cell disease suffer frequent vaso-occlusive phenomena due to sickle cell erythrocytes causing severe irreversible damage in particular on the retina due to compromise of the small terminal vessels. Retinal disease may be proliferative or non-proliferative with areas of intraretinal hemorrhage or arteriovenous anastomosis respectively. On cases of proliferative type, bleeds on the vitreous and subsequent vitreous degeneration, may lead to retinal detachment, and finally visual loss, more common on patients with hemoglobin SC. A serious complication of sickle cell anemia is hyphemia; the hemorrhage on the anterior chamber alters the aqueous humor circulation and increases the intraocular pressure with acute loss of vision. Predisposition to orbital wall infarction and orbital cellulitis are both present as orbital compression syndrome with inflammation.²⁴ The optic nerve may be compressed as well due to intraorbital hematoma.^9–11,23

Other ocular manifestations of sickle cell disease due to vascular occlusion may occur in the conjunctiva, iris, retina, and choroid affecting either the posterior or the anterior chambers of the ocular globes. The anterior chamber abnormalities secondary to sickle cell disease include corkscrew conjunctival vessels, infarcts and atrophy of the iris, cataracts, phthisis bulbi, and hyphemia.^2,9 The posterior chamber abnormalities can be divided into optic disc abnormalities, posterior retinal and maculae vascular occlusion, chronic vascular occlusion, and non-proliferative retinal changes. Endophthalmitis involving the posterior chamber of the globe frequently leads to blindness.²

Patients with hemoglobin SC (heterozygous) show higher prevalence to develop sickle cell retinopathy than those with hemoglobin SS (homozygous), however, the SS type demonstrated higher severity, as described by Leveziel et al. in a large series retrospective study.⁸

The association of endophthalmitis and sickle cell disease is rare. Few case reports have been published, a total of three cases.^2,12,13 In one case, the patient lost light perception.² In the remainder of cases,^12,13 the loss of visual acuity was the most remarkable symptom. In our case, the endophthalmitis led to bilateral blindness.

Endophthalmitis and infection

Infectious agents associated with endophthalmitis include gram positive organisms (Staphylococcus aureus, Streptococci species), gram negative organisms (Klebsiella, Pseudomonas, Serratia), and mycosis (Aspergillus, Candida).

Klebsiella was present in 23 of patients with liver abscess. Eighty-nine percent of this group of patients developed bilateral endogenous endophthalmitis in a study by Yang et al.¹⁴ In this study, almost half of the patients underwent enucleation despite aggressive treatment.^14,15

Streptococcus pneumoniae is an infrequent cause of endophthalmitis, generally related to eye surgery. For these patients, the prognosis is very poor.¹⁶ In a large retrospective study on patients with generalized candidiasis, 6 of 370 cases presented with endophthalmitis.^5,17

Serratia represents 4% of cases of endogenous endophthalmitis.¹⁸

Ocular cultures are negative in 40% of cases; therefore, the diagnosis relies mostly on blood cultures,¹² and, as in our case, on the findings on CT and MRI.^12,19

Radiologic features

In CT, findings of endophthalmitis include increased density within the vitreous chamber and uveoscleral enhancement and thickening. Other abnormalities found in CT are subconjunctival empyema, swelling of the eyelid, enlargement and enhancement of the lacrimal gland, and infiltration of the retro bulbar fat.¹⁵

In MRI, these cases reveal hyperintense T1-weighted and fluid-attenuated inversion recovery (FLAIR) signals within the vitreous chamber due to proteinaceous inflammatory content, with a thick diffuse or nodular uveal enhancement reflecting inflammation. In addition, restricted diffusion on diffusion-weighted and apparent diffusion coefficient (ADC) MRI is present during the active course of the disease being, therefore, helpful to monitor response to therapy. The normalization of diffusion-weighted images (DWI) and ADC values is considered a positive response to treatment reflecting improvement of the viscosity of the proteinaceous inflammatory content of the vitreous chamber, a principle similar to that of an abscess with restricted diffusion.^6,20–22

Retinal and choroidal detachments, which are potential complications of endophthalmitis, may be visualized on both CT and MRI. The majority of the patients with endophthalmitis are initially misdiagnosed as having either anterior uveitis or cellulitis. CT and MRI are helpful in the initial stages of the clinical assessment of these cases. In CT and MRI, orbital cellulitis will present as isolated fat stranding or edema of the pre-septal orbital soft tissues. In cases of acute uveitis, CT scan is not helpful. In chronic uveitis, CT scan may show uveoscleral thickening and enhancement and posterior uveal calcifications. In cases of acute uveitis, MRI can show restricted diffusion and increased gadolinium enhancement of the uveal tract and uveal effusions.

Conclusion

We presented a rare case of endophthalmitis in a patient with sickle cell disease and negative blood cultures. CT and MRI played an important role in providing an early diagnosis of endophthalmitis in this case.

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.