Severe Optic Neuroretinitis and Vitreous Hemorrhage in Pediatric Cat-Scratch Disease: A Case With Irreversible Visual Impairment

Introduction

Cat-scratch disease (CSD) is a zoonotic infection caused by Bartonella henselae, a facultative intracellular bacterium. Although cats are typically asymptomatic carriers, humans can acquire the infection through scratches or bites from infected cats, or indirectly via cat fleas, which act as vectors [1]. Typical CSD is a self-limiting condition characterized by a local skin lesion at the site of feline contact, followed by regional lymphadenitis with or without fever. However, CSD can occasionally present with organ-specific manifestations, including ocular involvement (eg, optic neuroretinitis or Parinaud’s oculoglandular syndrome), hepatosplenic granulomas, acute encephalopathy, and endocarditis. The majority of ocular complications associated with CSD resolve spontaneously and demonstrate favorable visual prognosis; however, cases with poor visual outcomes have also been reported [2]. B. henselae promotes angiogenesis through complementary mechanisms. Direct endothelial infection induces intracellular hypoxia, activates hypoxia-inducible factor-1 [3], and upregulates vascular endothelial growth factor (VEGF) signaling, while the VEGF-like autotransporter BafA can further stimulate VEGF receptor pathways [4]. In addition, persistence of B. henselae within mesenchymal stromal cells has been shown to enhance endothelial activation and infectability, thereby amplifying the angiogenic process and potentially establishing a self-sustaining angiogenic loop [5]. In the ocular setting, such pathways could plausibly contribute to VEGF-dependent vascular proliferation and the development of intraocular angiomatous or vasoproliferative lesions. In Japan, epidemiological data indicate that the majority of CSD cases occur in pediatric patients [6]. Here, we report a pediatric case of CSD with severe ocular involvement and poor visual outcome.

Case Report

A 6-year-old girl presented with a mild cough and decreased vision in her right eye, which she noticed following a sustained high fever (39°C) lasting 10 days; the visual disturbance was first recognized by her parents approximately 2 months later. On presentation to our hospital (day 1), her height and weight were 127 cm (Z-score +1.2) and 28.15 kg (Z-score +1.3), respectively, with a body mass index of 17.5 kg/m2 (Z-score +1.0), based on CDC Growth Charts. Her body temperature was 36.6°C. Her best-corrected visual acuity (BCVA) was counting fingers at 10 cm (corresponding to approximately 2.0–2.3 logMAR) in the right eye and 20/17 (−0.07 logMAR) with a spherical correction of +1.25 D in the left eye. Her intraocular pressure, measured with an iCare rebound tonometer, was 7 mmHg in the right eye and 13 mmHg in the left eye. The anterior segment findings were unremarkable. A slight relative afferent pupillary defect was noted in the right eye.

Goldmann visual field testing revealed a central scotoma in the right eye (Figure 1). Fundus examination revealed optic disc edema with surrounding exudates (Figure 2A), multiple exudates in all retinal quadrants (Figure 3A), posterior vitreous detachment extending into the midperiphery, preretinal hemorrhages, and mild vitreous hemorrhage. Optical coherence tomography (OCT) showed optic disc edema and serous macular detachment (Figure 2B). Fundus examination (Figure 2C) and OCT (Figure 2D) of the left eye showed no abnormal findings.

On physical examination, a linear abrasion consistent with a cat scratch was observed on her right cheek (Figure 4). The patient lived in a household involved in cat rescue and had frequent contact with multiple cats; thus, the exact timing of any cat scratch could not be determined. Laboratory tests showed a white blood cell count of 6700/μL (reference range for children: 4100–15 000/μL) with 31.4% neutrophils, 55.5% lymphocytes, 4.2% monocytes, 8.0% eosinophils, and 0.9% basophils. Peripheral blood smear showed no blasts or atypical lymphocytes. C-reactive protein was 0.15 mg/dL (reference range: <0.15 mg/dL). Serology was negative for Toxoplasma IgG (<3 IU/mL) and IgM (0.1 IU/mL), Treponema pallidum antibody, and tuberculosis-specific interferon gamma (IFN-γ). Brain magnetic resonance imaging, including short tau inversion recovery sequences, showed no optic nerve hyperintensity suggestive of optic neuritis and no evidence of space-occupying lesions. On day 4, pediatric evaluation was performed as part of the systemic workup. Ultrasonography revealed a small lymph node on each side of the neck. No hepatosplenomegaly was present.

Fluorescein angiography on day 7 revealed optic disc vascular dilation and leakage, blockage due to a preretinal hemorrhage extending from the disc to the posterior pole, and peripheral vascular leakage in all quadrants without evidence of vascular anastomosis (Figure 3B). The arm-to-retina circulation time was 17 seconds, and the posterior pole circulation time was 49 seconds.

Based on the unilateral vision loss following a fever, the presence of a cat scratch, and optic neuroretinitis with retinochoroiditis in the right eye, CSD was suspected. Serological testing for B. henselae and Bartonella quintana was ordered, and the patient was admitted 7 days after her initial hospital visit (Figure 5). Given the clinical features suggestive of severe CSD, and with other possible diagnoses – including optic neuritis, neuroretinitis of infectious or inflammatory origin, posterior uveitis, and neoplastic etiologies – having been excluded, treatment was initiated prior to serological confirmation. Azithromycin (300 mg/day) was administered on days 7–9. On day 11, oral prednisolone (15 mg/day, 0.5 mg/kg/day) was initiated. A second course of azithromycin (300 mg/day) was given on days 14–16. On day 10, BCVA in the right eye was 20/1000 and improved to 20/660 by day 14, which was the patient’s day of discharge.

On day 20, serology confirmed a B. henselae infection with IgM and IgG titers of 1: 40 and ≥1: 1024, respectively, while serology was negative for B. quintana antibodies, thereby confirming the diagnosis of CSD. Oral prednisolone was tapered over 3 months and then discontinued.

One month after the initiation of treatment, the patient’s serous retinal detachment had improved, with gradual resolution of optic disc edema and exudates. However, on day 113, BCVA in the right eye was 20/280 (1.15 logMAR), with improvement to 20/250 (1.10 logMAR) at 8 months and 20/200 (1.0 logMAR) at 13 months. Nineteen months after treatment initiation, the patient’s final BCVA in the right eye was 20/100 (0.7 logMAR). The optic disc edema, serous macular detachment, and exudates had resolved (Figure 6A). OCT revealed thinning of the retinal nerve fiber layer (RNFL) and the retinal ganglion cell layer (GCL), along with photoreceptor layer defects (Figure 6B). The RNFL thickness in the right eye measured 105 μm in the superior and 124 μm in the inferior quadrant (Figure 6B), whereas that in the left eye was 148 μm and 151 μm, respectively (data not shown). On Humphrey 10–2 testing, the total deviation and total deviation probability plots (Figure 6C) showed decreased central sensitivity consistent with a central relative scotoma, with foveal sensitivity of 20 dB in the affected right eye and 36 dB in the left eye (data not shown).

Discussion

This case illustrates a rare pediatric presentation of CSD complicated by severe optic neuroretinitis and retinochoroiditis, wherein intense and persistent inflammation led to prolonged optic disc edema and central serous retinal detachment. These complications resulted in damage to the retinal photoreceptor layer, thinning of the RNFL and GCL, a residual central relative scotoma, and irreversible visual impairment.

Previous studies have reported that 74–84% of patients with ocular complications achieve a final visual acuity of 20/28 or better [7–9]. Cases of CSD resulting in a final visual acuity of 20/200 or worse are uncommon, with reported rates ranging from 0% to 13.5% [2,7,10,11]. Posterior ocular complications of CSD include optic neuroretinitis, retinochoroiditis, retinal artery occlusion, retinal vein occlusion, retinal infiltrates, and angiomatous lesions [1,2,7,8,10]. Retinochoroiditis is generally associated with a poorer visual prognosis than optic neuroretinitis and may also be accompanied by telangiectasia or angiomatous-like proliferation of retinal capillaries [2]. In a study by Curi et al, angiomatous lesions were observed in 4 of 5 eyes with a final visual acuity of 20/200 or worse [11]. B. henselae is known to infect vascular endothelial cells [12], and these vascular alterations are thought to result from vasculoproliferative processes induced by activation of VEGF receptors [3,4,5]. In this case, fluorescein angiography demonstrated vasoproliferative changes resembling angiomatosis associated with peripapillary vascular dilation and marked fluorescein leakage from the peripheral retinal vessels. The extensive and protracted retinochoroiditis suggested irreversible loss of the retinal photoreceptor layer. Additionally, posterior vitreous detachment, which is extremely rare in children, was observed and accompanied by vitreous hemorrhage, likely reflecting the severity of the retinochoroiditis. In pediatric uveitis, such as pars planitis, inflammation-related alterations of the vitreoretinal interface can weaken vitreoretinal adhesion and promote vitreous liquefaction, leading to premature posterior vitreous detachment [13]. Accordingly, in the present case, the observed posterior vitreous detachment and vitreous hemorrhage might have been secondary to severe inflammatory retinochoroiditis, and may serve as indicators of severe and sustained intraocular inflammation. In pediatric patients, posterior vitreous detachment is extremely rare and may thus serve as a strong indicator of disease severity. Marked optic disc inflammation was also present. After resolution of the disc inflammation, thinning of the RNFL was noted in the superior and inferior quadrants compared with that in the fellow eye. Prominent thinning of the GCL was also observed. In cases such as this, where severe optic neuroretinitis and retinochoroiditis occur, damage to both the inner and outer retinal layers can lead to residual central visual field defects and poor final visual acuity.

Because of the strong clinical suspicion of CSD and the severity of ocular inflammation, treatment was initiated empirically prior to serological confirmation. Although the linear scratch observed on the cheek appeared to be relatively recent and was not temporally consistent with symptom onset 2 months earlier, the patient lived in a household engaged in cat rescue and was frequently surrounded by cats. This context suggests repeated exposure to B. henselae, supporting the clinical suspicion of CSD. Treatment strategies for ocular CSD with ocular complications vary and may include observation without therapy, antibiotics alone, or a combination of antibiotics with systemic corticosteroids. However, these strategies are based on case reports and case series. Consequently, outcomes are inconsistent; it remains unclear which treatments, at what timing, and in which combination they should be administered to achieve better visual outcomes, or whether observation alone is appropriate. Intravitreal anti–VEGF therapy subsequent to systemic antimicrobial therapy may be a potential adjunctive treatment for choroidal neovascularization associated with CSD [14,15]. However, owing to the lack of randomized controlled trials, the optimal evidence-based treatment for ocular manifestations of CSD has not yet been established [7]. Treatment in this case involved the concurrent administration of antibiotics and oral prednisolone. Based on reports demonstrating high susceptibility of B. henselae strains isolated from Japanese cats and humans to minocycline and macrolide antibiotics [16], Fukuda et al selected azithromycin for their case series [7]. Furthermore, as the same study reported the use of corticosteroids in combination therapy for cases with severe visual impairment, we also followed this approach. Importantly, as demonstrated here, prolonged inflammation carries a high risk of poor visual prognosis. To our knowledge, no previous study has directly examined the impact of the interval between the onset of visual acuity loss and initiation of treatment on visual outcomes in ocular CSD; however, Reed et al [17] reported that prompt treatment led to rapid and favorable visual acuity, whereas delayed treatment (approximately 2 months after symptom onset) was associated with slow resolution of ocular findings and limited visual improvement. In the case report by Hamada et al [18], systemic antibiotic therapy was initiated approximately 6 weeks after the initial visual loss. During this interval, the disease progressed from unilateral to bilateral involvement, and the visual outcome was poor, with no light perception in the right eye. Similarly, treatment in the present case was also delayed, and the final visual outcome was poor. Although both are single case reports, the 2 cases reported severe retinochoroiditis accompanied by vitreous hemorrhage. Taken together, the clinical courses of these 2 cases suggest that delayed treatment and its associated prolonged intraocular inflammation may lead to irreversible damage of both the outer and inner retina, resulting in poor visual outcomes despite appropriate therapy. These observations collectively underscore the importance of early diagnosis and timely therapeutic intervention for preventing irreversible visual dysfunction in ocular CSD.

Conclusions

This case describes a presentation of pediatric ocular CSD with severe optic neuroretinitis and retinochoroiditis, resulting in irreversible visual impairment despite combined antibiotic and corticosteroid therapy. Posterior vitreous detachment with vitreous hemorrhage, an exceptionally rare finding in children, reflected the severity of intraocular inflammation. While definitive evidence for the superiority of specific treatments is lacking, this case suggests that persistent inflammation can lead to poor visual outcomes. Delayed identification of visual impairment may result in progression to severe ocular damage; therefore, clinicians should be vigilant for subtle visual changes in children following febrile illness and consider CSD in the differential diagnosis because children often fail to recognize or articulate their own visual loss. Early recognition is crucial to prevent irreversible retinal damage.