Contrast‐Enhanced Ultrasonography of Orbital and Intraocular Pathologies in 24 Dogs and 6 Cats

ABSTRACT

Objective

Contrast‐enhanced ultrasonography (CEUS) is a noninvasive and relatively safe imaging technique to assess ocular perfusion, showing high sensitivity and specificity for tumor characterization in human oncology, while reports on its application in canine and feline diseased eyes are limited. This study aimed to describe the CEUS features of orbital and intraocular pathologies in dogs and cats in order to evaluate its diagnostic value in detecting and characterizing various lesions.

Animal Studied

CEUS examinations of 30 animals (24 dogs, 6 cats) were evaluated retrospectively.

Procedures

Following B‐mode ultrasonography, CEUS examinations utilizing sulfur hexafluoride were performed. Pathologies were categorized in one of the following groups: orbital neoplastic lesions, orbital inflammatory lesions, intraocular neoplastic lesions, intraocular inflammatory lesions and retinal detachment. Qualitative perfusion parameters, contrast intensity, enhancement pattern, perfusion type and time to wash‐in and wash‐out were evaluated.

Results

CEUS detected vascularization in orbital and intraocular pathologies, with variable enhancement characteristics. Persistent vascularization was observed in all cases of retinal detachment. In orbital and intraocular neoplastic lesions, CEUS improved lesion localization, assessment of interactions with surrounding tissues and tissue perfusion. For inflammatory pathologies such as abscesses, myositis, and steatitis, the additional diagnostic value of CEUS compared to B‐mode ultrasonography was limited.

Conclusion

Findings indicated that CEUS could identify a variety of orbital and intraocular pathologies and provided additional diagnostic information to B‐mode ultrasonography, particularly for assessing neoplastic lesions and retinal detachments. CEUS has the potential to enhance ophthalmic ultrasonography in differentiating specific pathologies. Prospective studies are warranted to further evaluate its clinical use.

1. Introduction

Successful treatment of ocular pathologies depends on accurate diagnosis. When opacities are present in the ocular media, whether inflammatory, degenerative, or of other origin, they can complicate ophthalmic examination and thereby limit targeted diagnosis [1, 2, 3]. For further evaluation, B‐mode ultrasonography is most commonly performed as a noninvasive, cost‐effective method to visualize ocular and orbital structures, allowing more precise assessment of existing pathologies [4, 5, 6, 7]. However, its diagnostic value varies among diseases [8]. High‐resolution ultrasonography and ultrasound biomicroscopy can provide detailed information on the anterior segment, but are less suitable for evaluating the posterior segment and periocular regions [7, 9]. Color‐ and Power Doppler imaging are susceptible to artifacts caused by eye movements, making interpretation more difficult [10]. In addition, visualization of blood flow in small vessels with low blood flow velocities remains challenging, as overall tissue motion may exceed capillary blood flow [8, 11, 12].

Contrast‐enhanced ultrasonography (CEUS) has gained diagnostic importance in both veterinary and human medicine. It is a noninvasive technique that may aid in differentiating retinal detachment from vitreal membranes in dogs and cats [10]. In contrast to Doppler methods, CEUS allows visualization of smaller vessels in dogs, cats, and humans [10, 12, 13, 14]. Blohm et al. [15] demonstrated that the contralateral eye can serve as a reliable in vivo reference and that vascular enhancement should be evaluated within 60 s after sulfur hexafluoride administration in beagles without ocular pathologies.

In human oncology, CEUS is a useful diagnostic technique for tumor characterization and therapeutic management [16, 17]. It shows high sensitivity and specificity for the diagnosis of orbital space‐occupying lesions and may be beneficial in differentiating benign from malignant intraocular tumors [18, 19]. In patients responding to chemotherapy, a gradual reduction in neoplastic blood supply has been observed [16, 17]. Only a few studies have reported CEUS applications in canine and feline eyes with neoplastic lesions [20, 21]. Andreani et al. [20] postulated CEUS to be superior to Color Doppler in detecting blood flow within intraocular masses. Quarta et al. [21] reported contrast enhancement in both normal and neoplastic feline uvea, with subjectively increased vascularization in eyes with suspected neoplasia.

Altogether, these findings support CEUS as a promising, noninvasive, and sensitive method to evaluate blood flow in ocular pathologies [10, 12, 15, 20, 21].

The aim of this retrospective study was to describe the CEUS appearance and perfusion characteristics of orbital and intraocular lesions in dogs and cats. We hypothesized that CEUS provides additional diagnostic value to conventional B‐mode ultrasonography.

2. Material and Methods

2.1. Animals

This retrospective study included dogs and cats with orbital and/or intraocular lesions that underwent CEUS at the University of Veterinary Medicine Vienna from January 2016 to July 2017 and were recorded in the electronic medical records system. Inclusion criteria were a complete ophthalmologic examination, conventional B‐mode ultrasonography, and CEUS.

Patient data and medical history including examination results from the initial presentation of the patients at the ophthalmology unit of the University of Veterinary Medicine Vienna were retrieved from the database. Collected information comprised age, sex, weight, breed, ophthalmic and ultrasonographic findings, and interventions following diagnosis. When available, additional imaging findings (radiographs, computed tomography [CT], magnetic resonance imaging [MRI]) as well as bacteriological, pathological, and cytological results were collected. Follow‐up examination results, disease progression and concurrent pathologies were also considered. In cases without a definitive diagnosis, the final diagnosis was determined based on all available criteria, with particular emphasis on the results of diagnostic‐surgical procedures and the therapeutic response.

2.2. B‐Mode and Contrast‐Enhanced Ultrasonography

All CEUS examinations were preceded by B‐mode ultrasonography. Examinations were performed using either a 12–5 MHz linear transducer or an xMATRIX sector transducer with PureWave crystal technology, operating within a frequency range of 6–1 MHz (IU22; Philips, Bothell, WA). A coupling gel was applied to ensure acoustic coupling between the transducer and the eyelids. Ultrasonography was performed transpalpebrally under topical anesthesia using oxybuprocaine hydrochloride ophthalmic drops (Novain; Agepha, Vienna, Austria), with animals either awake or sedated depending on their cooperation. In patients scheduled for surgery, examinations were conducted under general anesthesia.

Contrast imaging was performed using sulfur hexafluoride (SonoVue; Bracco, Milan, Italy) following the technique described by Blohm et al. [15] with a transpalpebral rather than transcorneal transducer placement. The contrast agent was administered via the cephalic vein in all animals except one (D5—V. saphena lateralis). Sixteen patients (11 dogs, 5 cats) received a dose of 0.03 mL/kg [22, 23], six patients (5 dogs, 1 cat) received a dose of 0.5 mL per animal and eight dogs received a dose of 1 mL per animal determined by body weight (< 20 kg: 0.5 mL, > 20 kg: 1 mL) as per O'Brien et al. [23, 24]. The mechanical index (MI) ranged from 0.05 to 0.10 for all examinations.

During each contrast study, a 2‐min video clip of either the vertical or horizontal scan was recorded immediately after contrast administration and digitally stored (dicomPACS View Version 6.0.2, 457, Bodmin, UK; Oehm und Rehbein, Rostock, Germany). All procedures were performed by the same radiologist (K.M.H.) and ophthalmologist (K.O.B.), who were not blinded to the ophthalmologic findings.

Pathologies were categorized into five groups: orbital neoplastic lesion, orbital inflammatory lesion, intraocular neoplastic lesion, intraocular inflammatory lesion, and retinal detachment. Contrast intensity (CI: strong, moderate, low, variable) and enhancement pattern (EP: heterogeneous, homogeneous, rim) were qualitatively analyzed for each lesion type. For solitary lesions, CEUS evaluation included lesion visibility, perfusion type (centrifugal, centripetal, diffuse, chaotic, rim) and the timing of wash‐in (WI), wash‐out (WO) and contrast retention relative to surrounding tissue whenever these features were assessable from the available recordings. The different perfusion types were defined as follows: centrifugal perfusion was defined as enhancement originating in the central portion of the lesion and progressing toward the periphery, whereas centripetal perfusion was defined as enhancement beginning at the periphery and progressing toward the center. Diffuse perfusion was characterized by enhancement involving the entire lesion, with the whole pathological area showing enhancement and without a clearly identifiable directional progression. Rim perfusion was defined as predominantly peripheral enhancement along the outer margin of the lesion, with absent or markedly reduced central perfusion. Perfusion was classified as chaotic when it could not be consistently assigned to any of the aforementioned patterns and no predominant or reproducible perfusion pattern could be identified.

Qualitative descriptors of enhancement dynamics were based on measurements obtained from the recorded CEUS examinations, including WI and WO. The following study‐specific definitions were applied: rapid wash‐in ≤ 10 s after intravenous contrast administration (ICA); slow wash‐in > 10 s after ICA; rapid wash‐out ≤ 60 s after ICA; delayed wash‐out > 60 s after ICA. In eyes with multiple lesions, the pathology most relevant to the clinical presentation was analyzed. All ultrasonographic examinations were retrospectively reviewed by three authors (J.I.O., K.M.H., K.O.B.).

3. Results

Thirty animals (36 eyes) met the inclusion criteria, comprising 24 dogs (29 eyes) and six cats (7 eyes), with some animals presenting bilateral lesions. Signalment, diagnosis, and affected eye are documented in Table 1. Most examinations were performed in conscious animals (25 animals). Sedation was necessary in three patients, and two animals were examined under general anesthesia. The 12–5 MHz linear transducer was used in 25 animals, while the xMATRIX sector transducer with PureWave crystal technology (6–1 MHz) was used in five animals.

TABLE 1.

Signalment, diagnosis and affected eye of dogs and cats included in the study.

Case	Signalment	Diagnosis
D1	Golden Retriever, female spayed, 33 kg, 12 years	OS Retinal detachment and glaucoma
D2	Labrador Retriever, male neutered, 30.9 kg, 10 years	OS Melanoma
D3	Border Collie, male neutred, 24 kg, 11 years	OS Adenocarcinoma
D4	Pit Bull Terrier, male, 30 kg, 9 years	OD Inflammatory pseudotumor
D5	German shepherd, female, 22 kg, 8 years	OS Abscess
D6	French Bulldog, female spayed, 10.2 kg, 11 years	OU Steatitis
D7	Chihuahua, female spayed, 4 kg, 7 years	OS Steatitis
D8	Labrador Retriever, female, 25.5 kg, 1 year	OS Endophthalmitis
D9	Wire‐haire dachshund, male neutered, 8.2 kg, 1 year	OS Abscess
D10	Mixbreed, male neutered, 23 kg, 7 years	OD Myositis, Steatitis
D11	Mixbreed, male neutered, 12 kg, 1 year	OD Abscess
D12	Dalmatiner, female, 28 kg, 7 years	OU Myositis
D13	Mixbreed, male, 4.55 kg, 11 years	OU Retinal detachment and hemorrhage
D14	Dachshund, male, 8.50 kg, 8 years	OS Myositis
D15	Labrador Retriever, male, 29 kg, 10 years	OD Neoplasia of neuroectodermal origin
D16	Shi Tzu, female spayed, 6.4 kg, 15 years	OU Retinal detachment and hemorrhage
D17	Maltese, male, 8 kg, 9 years	OD Myositis versus Steatitis
D18	Mixbreed, male neutered, 23 kg, 9 years	OS Retinal detachment and hemorrhage
D19	Whippet, male, 16 kg, 2 years	OD Abscess
D20	Mixbreed, female, 13 kg, 4 years	OU Uveitis
D21	CKCS, female spayed, 8 kg, 5 years	OD Myositis, Steatitis
D22	Catalan Sheepdog, male neutred, 31 kg, 7 years	OS Canine orbital meningioma
D23	Cocker Spaniel, male, 17.5 kg, 10 years	OS Melanoma
D24	Dachshund, female spayed, 6.20 kg, 9 years	OS Retinal detachment and hemorrhage
C1	Domestic short hair, female spayed, 4.4 kg, 12 years	OD FROMS
C2	Birma, male neutered, 1 year	OD Uveitis
C3	Domestic short hair, female spayed, 4.80 kg, 4 years	OU Myositis
C4	Domestic short hair, female spayed, 3.0 kg, 16 years	OD Malignant lymphoma
C5	Domestic short hair, male neutered, 3.9 kg, 5 years	OS Abscess
C6	Domestic short hair, female spayed, 3.9 kg, 13 years	OS Myositis, Steatitis

Abbreviations: C, cat; CKCS, Cavalier King Charles Spaniel; D, dog; kg, kilogram; OD, oculus dexter; OS, oculus sinister; OU, oculus uterque.

A side to side comparison of the lesions is seen in Table 2.

TABLE 2.

Lesion characteristics.

Lesion	Case	Enhancement pattern	Perfusion type	Contrast intensity	Wash‐in	Wash‐out	Additionally findings
Adenocarcinoma	D3	Heterogeneous	Centripetal	Strong	Rapid, surrounding tissue first	Delayed, began centrally	Individual vessels on the surface
Orbital meningioma	D22	Heterogeneous	Centrifugal	Moderate	Slow, lesion first	Rapid, surrounding tissue first	—
FROMS	C1	Heterogeneous	Diffuse	Strong	Rapid	Rapid, surrounding tissue first	Not clearly delineated from the surrounding tissue
Lymphoma	C4	Homogeneous	Centrifugal	Strong	Rapid	Rapid, lesion first	—
Abscess	D5, D9, D11, D19, C5	Rim	Rim	Moderate–strong	Slow	Delayed	Not always visible
Myositis/steatitis	D6, D7, D10, D12, D14, D17, D21, C3, C6	Heterogeneous	Chaotic	Variable	Variable	Variable	Linear contrast filling defect
Inflammatory pseudotumor	D4	Homogeneous	Centripetal	Strong	Rapid	Rapid	Decreasing CI toward the center
Melanoma	D2, D23	Homogeneous	Centripetal	Strong	Rapid, lesion first	Rapid	—
Neuroectodermal neoplasm	D15	Homogeneous	Centrifugal	Moderate	Slow	Delayed	More intense contrast intensity centrally
Endophthalmitis	D8	Homogeneous	Diffuse	Moderate	Rapid	Delayed	—
Uveitis	D20, C2	Homogeneous	Diffuse	Moderate–strong	Rapid	Delayed, rostral → caudal	—
Retinal detachment	D1, D13, D16, D18, D24	Persistent retinal enhancement	—	Variable	—	—	—

Note: Rapid wash‐in ≤ 10 s ICA; slow wash‐in > 10 s after ICA rapid wash‐out ≤ 60 s after ICA; delayed wash‐out > 60 s after ICA.

Abbreviations: C, cat; D, dog; FROMS, feline restrictive orbital myofibroblastic sarcoma; ICA, intravenous contrast agent.

3.1. Orbital Neoplastic Lesions

Two dogs (2 eyes) and two cats (2 eyes) exhibited orbital neoplastic lesions. Histopathology confirmed the diagnosis in all animals.

The nictitating membrane adenocarcinoma appeared on B‐Mode ultrasound as a 2.2 × 2.5 cm hypoechoic, round mass displacing the globe dorsally and temporally. On CEUS there was a rapid WI. The surrounding tissue enhanced first, followed by visualization of individual vessels on the lesion's surface, with heterogeneous centripetal enhancement and strong CI. The WO was delayed and began centrally. Peripheral vessels remained visible for a longer duration, with some intermittent centripetal enhancement.

Canine orbital meningioma appeared on B‐mode ultrasound as a 2.1 × 2.4 cm heterogeneous, hypoechoic to hyperechoic solid mass. On CEUS, a slow WI was first observed within the mass, followed by adjacent tissue. Microbubbles circulated in a centrifugal pattern with subsequent moderate CI and heterogeneous enhancement, predominantly central. Adjacent tissue showed lower CI compared to the mass. A rapid WO was observed in the surrounding tissue, followed by the mass.

Feline restrictive orbital myofibroblastic sarcoma (FROMS) appeared heterogeneously hyperechoic with a mass effect in the periocular space, compressing the globe without significant exophthalmos. After contrast administration, the mass could not be clearly delineated from surrounding soft tissue. Following rapid contrast uptake, the orbital space showed a strong CI and heterogeneous enhancement pattern throughout the affected orbital space. The perfusion type was diffuse. Contrast persisted longer in the pathological tissue than in adjacent structures and showed a rapid WO.

Malignant lymphoma was located retrobulbar on B‐mode ultrasound as a 2.4 × 1.73 cm irregular, hypoechoic mass displacing the globe dorsally and temporally. CEUS revealed rapid centrifugal enhancement, followed by a strong CI, and homogeneous enhancement pattern in the mass (Figure 1). After a short retention WO began within the mass, followed by the surrounding tissue.

FIGURE 1.

A 16‐year‐old spayed female domestic shorthair with malignant lymphoma (C4). (1) B‐mode ultrasound reveals a 2.4 × 1.73 cm heterogeneous hypoechoic retrobulbar mass (+). (2) (A–D with time shown relative to contrast injection): Following contrast application, homogeneous centrifugal enhancement with subsequent strong CI.

3.2. Orbital Inflammatory Lesions

Orbital inflammatory lesions were diagnosed in 12 dogs (14 eyes) and three cats (4 eyes). Lesions included five abscesses (5 eyes), two cases of steatitis (3 eyes), three cases of extraocular orbital myositis (5 eyes), and three cases of concurrent steatitis and myositis (3 eyes). One equivocal case (myositis versus steatitis 1 eye) and one patient with unilateral lymphohistiocytic inflammation of the nictitating membrane (1 eye) were also recorded. Abscesses were confirmed in all cases by surgical exploration. Myositis and/or steatitis were presumed in 7 of 9 animals (9/12 eyes) based on response to therapy. Clinical improvement and resolution of lesions were observed during follow‐up under various systemic treatment regimens, including nonsteroidal or steroidal anti‐inflammatory therapy, with or without additional broad‐spectrum antibiotic treatment. Lymphohistiocytic inflammation of the nictitating membrane was confirmed histopathologically.

Abscesses (5 eyes) appeared on B‐mode ultrasound as predominantly hypoechoic lesions containing some echogenic particles (1 eye, Figure 2) to anechoic rounded lesions (2 eyes) or partially septated lesions (1 eye). In two cases (2 eyes), conventional ultrasonography failed to detect surgically confirmed abscesses. In these cases, the retrobulbar region appeared heterogeneously hyperechoic.

FIGURE 2.

A 2‐year‐old intact male whippet with suspected retrobulbar and peribulbar abscess of the right eye (D19). A retrobulbar abscess was confirmed intraoperatively. (1) B‐mode ultrasonography shows a 1.4 cm wide, partially septated, anechoic zone in the retrobulbar area (+). (2) (A–D with time shown relative to contrast injection): After contrast application, the retrobulbar space shows heterogeneous enhancement, with pronounced sparing of the abscess (rim enhancement) (+).

Following contrast administration, abscesses demonstrated slow contrast wash‐in with delayed wash‐out (3 eyes). One lesion was characterized as a non‐vascularized cavity with contrast uptake in the surrounding tissue (rim enhancement, 1 eye). When both the abscess capsule and its contents enhanced, the abscess interior exhibited lower contrast intensity compared to the capsule (2 eyes).

In the two cases not visualized by B‐mode ultrasonography, CEUS also failed to demonstrate abscess‐specific enhancement characteristics. Instead, the retrobulbar space exhibited moderate (1 eye) to strong (1 eye) CI with a heterogeneous enhancement pattern (2 eyes).

Extraocular orbital myositis was characterized on conventional ultrasound by hypoechoic thickening of the retrobulbar muscles (8 eyes) and heterogeneous surrounding tissue (4 eyes). Myositis was observed either with (5 eyes) or without (5 eyes) concurrent steatitis.

Steatitis was characterized on B‐mode ultrasound by hyperechoic and heterogeneous retrobulbar fat (5 eyes), with associated retrobulbar edema in two eyes. CEUS revealed a predominantly heterogeneous enhancement pattern with variable WI, WO, and CI in both thickened muscle and affected fat tissue (12 eyes). Steatitis was further characterized by high contrast uptake within the retrobulbar fat in one eye. In another case (1 eye), a linear contrast filling defect within the ocular muscles was noted. Bilateral lesions demonstrated identical enhancement patterns.

Lymphohistiocytic inflammation of the nictitating membrane (inflammatory pseudotumor) was visualized ultrasonographically as a solid, homogeneous, peribulbar, nasal mass compressing and displacing the globe and adjacent tissues. On CEUS, the lesion exhibited a rapid WI with a centripetal perfusion type and a homogeneous enhancement pattern with progressively decreasing contrast intensity toward the center. The overall CI was strong. The WO was rapid (Figure 3).

FIGURE 3.

A 9‐year‐old intact male pit bull terrier with lymphohistiocytic inflammation of the nictitating membrane (inflammatory pseudotumor) (D4). (1) B‐Mode ultrasound shows a 3 × 4.6 cm solid peribulbar mass (*) nasal to the eye. (2) (A–D with time shown relative to contrast injection): CEUS reveals a centripetal perfusion type, followed by a homogeneous filling and an overall strong CI. A lower CI in the center was observed.

3.3. Intraocular Neoplastic Lesions

Intraocular neoplastic lesions were identified in three dogs (3 eyes). Histopathology confirmed melanoma in two dogs (2 eyes) and neoplasia of neuroectodermal origin in one dog (1 eye).

Melanoma appeared on B‐mode ultrasound either as a 1.45 × 0.63 cm round, hyperechoic mass originating from the iris with extension over the ciliary body, caudally into the choroid, and into the vitreous body (1 eye), or as an 8.15 × 4.3 mm round, hypoechoic mass in the medial iris (1 eye). With CEUS, both melanomas demonstrated a rapid WI with a slightly earlier enhancement of the lesion than surrounding tissue. One lesion demonstrated a centrifugal perfusion type and subsequently appeared isoenhanced to the surrounding tissue. In the other lesion, vessels extended from the sclero‐chorioretinal rim into the neoplasm. Both lesions exhibited an overall strong CI and homogeneous enhancement pattern. Wash‐out initiated centrally in one eye, whereas in the other eye, it began in the pupillary area and progressed across the mass toward the ciliary body. The WO was rapid in both lesions (Figure 4).

FIGURE 4.

A 10‐year‐old intact male cocker spaniel with a hypopigmented uveal melanoma in the left eye (D23). (1) B‐Mode ultrasound shows a hypoechoic lesion (*) in the medial iris, measuring 8.15 × 4.3 mm. Additionally, posterior lens luxation, cataract (white arrow), and retinal detachment (green arrow) are visible in the left eye. (2) (A–D with time shown relative to contrast injection): post‐contrast, the lesion enhanced homogeneously with a strong CI from the periphery to the center (centripetal). The surrounding region shows comparatively lower contrast enhancement. Retinal perfusion is not visible on CEUS.

The neuroectodermal neoplasm appeared on B‐mode ultrasound as a 6 mm, hyperechoic mass on the medial iris, extending from nasal to temporal. After contrast administration, slow WI was predominantly intralesional, with fine vessels exhibiting a centrifugal enhancement type and more intense contrast centrally. The round mass presented with moderate CI and a homogeneous enhancement pattern. Following a delayed WO, contrast intensity decreased from the periphery toward the center.

3.4. Intraocular Inflammatory Lesions

Intraocular inflammatory lesions were seen in two dogs (3 eyes) and one cat (1 eye). These included one case of endophthalmitis (1 eye) confirmed by pathology and two cases of uveitis (3 eyes), confirmed by positive anti‐inflammatory therapeutic response.

Endophthalmitis was caused by a 1.5 cm long, hyperechoic linear foreign body visible on B‐mode ultrasonography. Additional findings included hyperechoic iris thickening and echogenic particles in the anterior chamber and vitreous. On CEUS, the affected regions (sclero‐chorioretinal rim, anterior uvea) showed rapid WI with moderate CI and a homogeneous enhancement pattern in the sclero‐chorioretinal region. No contrast enhancement was observed within the foreign body or the intraocular particles. The WO was delayed.

Uveitis appeared on conventional ultrasound as a hyperechoic thickening, particularly in the choroid. On CEUS, lesions demonstrated rapid WI (Figure 5). Microbubbles spread homogeneously from the sclero‐chorioretinal area (3 eyes) into the anterior uvea, with CI ranging from moderate (2 eyes) to strong (1 eye). The WO occurred in the opposite direction, from rostral to caudal and was overall delayed. In cases of bilateral uveitis, enhancement patterns were identical.

FIGURE 5.

A 1‐year‐old neutered male birman cat with uveitis in the right eye (C2). (1) B‐Mode imaging shows a deepened anterior chamber (dashed line), a hyperechogenic line in front of the lens (arrow), and a distinctly outlined ciliary body (circle). The posterior segment appears markedly echogenic. (2) (A–D with time shown relative to contrast injection): post‐contrast, the uvea exhibits a strong CI. Additionally, a significant widening of the contrast‐enhanced uvea is observed on CEUS.

3.5. Retinal Detachment

Retinal detachment was diagnosed in five dogs (7 eyes) based on clinical findings and ophthalmologic examination (7/7 eyes) and confirmed by pathology in 2/7 eyes. Concurrent findings included intraocular hemorrhage (6 eyes) and glaucoma (1 eye).

On B‐mode ultrasonography, retinal detachment appeared as a convex or V‐shaped hyperechoic structure extending from the ocular fundus into the vitreous. In six eyes, coexisting hemorrhage produced hyperechoic structures with similar echogenicity to detached retina, precluding definitive diagnosis on B‐mode alone. On CEUS, retinal perfusion was consistently identified (7/7 eyes), facilitating differentiation from remaining non‐enhanced hyperechoic structures (hemorrhage). In 3/7 eyes, microbubbles exhibited oscillating movement along the detached retina (Figure 6). In bilateral retinal detachments (2 dogs, 4 eyes), the retina appeared isointense in one case and showed variable CI in the other. In the eye affected by glaucoma, CI of the retina was reduced and predominantly heterogeneous.

FIGURE 6.

A 11‐year‐old intact male mixed breed dog with bilateral retinal detachment due to suspected neoplasia (D13). (1) B‐Mode ultrasound of the right eye shows a hyperechoic structure in the vitreous. (2) (A–D with time shown relative to contrast injection): CEUS differentiated the perfused retina (arrows) from the other hyperechoic (non‐enhancing) structures in the vitreous. Movement of microbubbles along the retina was observed.

4. Discussion

This study demonstrated that CEUS effectively visualized orbital and intraocular lesions and revealed distinct enhancement patterns, particularly for intra‐ and extraocular neoplastic lesions. In addition, CEUS consistently detected persistent retinal perfusion in cases of retinal detachment.

In veterinary ophthalmology, CEUS is a noninvasive, relatively safe imaging technique to assess perfusion in both normal and diseased eyes [10, 12, 15, 20, 21]. Unlike previous studies focusing on single species or breeds, the present case series included CEUS examinations of dogs and cats of varying ages, sexes, and breeds, thereby reflecting routine clinical settings. Notably, most CEUS examinations were performed in awake animals, indicating that sedation is not routinely required. This observation aligns with the findings of Blohm et al. [15], who quantitatively analyzed intra‐ and extraocular perfusion in 10 awake beagles and hypothesized that CEUS may be well tolerated even in painful conditions under local anesthesia [15]. The present results support this assumption, as several included patients exhibited clinical signs of ocular pain yet tolerated the procedure.

There are only a few studies reporting the use of CEUS in diseased canine and feline eyes [10, 20, 21]. In retinal detachments, contrast enhancement indicates vascularized retina, whereas vitreal membranes remain avascular [10]. In the present study, CEUS enabled the differentiation of the detached retina from hyperechoic material within the vitreous body by demonstrating persistent retinal vascularization, thereby facilitating the diagnosis of retinal detachment. This finding is consistent with veterinary and human studies by Labruyere et al. [10] and Sconfienza et al. [16], respectively. In addition, bidirectional movement of microbubbles along the retina was observed in some eyes, suggesting persistence of both arterial and venous blood flow [10]. In cases of bilateral retinal detachment due to systemic disease, CEUS results showed identical enhancement patterns in both eyes. However, the eye with concurrent glaucoma demonstrated subjectively reduced perfusion, most likely reflecting the impact of elevated intraocular pressure on vessel diameter and blood flow, which manifests as decreased CI on CEUS [25].

Retinal reattachment within 4 weeks or less is associated with a more favorable prognosis in canine and feline patients [10, 26]. CEUS represents a reliable method for assessing retinal vitality and may help predict the likelihood of success or failure of vitreoretinal surgery, even when the duration of detachment is unkown [10].

In cases of neoplasia in canine and feline eyes, CEUS has been suggested to be superior to Color and Power Doppler ultrasonography for detecting blood flow within intraocular masses and identifying increased vascularization in suspected neoplasia [20, 21].

Similar to prior reports [19, 27], the cases of melanoma in this series demonstrated centripetal enhancement, a homogeneous pattern, strong CI, and shorter contrast retention in the lesion than in the surrounding tissue. Differing from the prior study [27], contrast uptake was observed in these lesions slightly earlier than the surrounding tissue. Wash‐in and WO characteristics were inconsistent across studies; however, similar to the cases in the present study, there was an overall tendency toward rapid WI and rapid WO [18, 19]. Another publication [16] highlighted the potential of CEUS in the assessment of choroidal melanoma, emphasizing its ability to demonstrate the pronounced vascularization typical of melanoma and to distinguish it from choroidal nevi, as well as its utility in monitoring treatment response after radiotherapy through the detection of a gradual decline in tumor blood flow. In the present case series, two melanomas were evaluated, which exhibited consistent enhancement patterns despite differing locations. Although no cases of feline diffuse iris melanoma were included, the application of CEUS in this diagnostically challenging condition warrants further investigation.

In human ophthalmology, CEUS is recognized as a suitable imaging technique for the diagnosis of orbital space‐occupying pathologies [19]. For differentiating benign from malignant intraocular tumors, a sensitivity of 98.3% and specificity of 100% has been reported [18]. Malignant tumors (e.g., choroidal melanoma, choroidal metastasis and retinoblastomas) are typically characterized by a rich blood supply, with CEUS demonstrating rapid WI, short time‐to‐peak, strong hyperechoic signal, and rapid WO [19]. This behavior reflects tumor‐induced angiogenesis, resulting in abundant abnormal arterial and venous vessels with high blood volume. In contrast, benign lesions are characterized by low‐velocity flow within thin‐walled venous vasculature, which explains their distinct enhancement patterns on CEUS. Benign lesions such as hemangiomas, melanocytomas, calcifications and pseudotumors, typically exhibit rapid WI with slow WO [18, 19].

In our case series, the canine pseudotumor exhibited a rapid homogeneous, centripetal enhancement, with the central region displaying lower contrast intensity compared to the periphery and a rapid WO. A direct comparison of WI and WO characteristics with surrounding tissue was not feasible as we focused on imaging of the lesion's perfusion as accurately as possible; the imaging window included only the pseudotumor without adjacent reference tissue. The centrally reduced contrast intensity may reflect areas of central necrosis within the lesion. This interpretation is supported by previous findings, where “filling defects” have been proposed as a possible imaging correlate of central necrosis. Notably, even in cases with histopathologically confirmed central necrosis, such imaging features may not always be explicitly emphasized, highlighting the subtlety of this finding on CEUS [19].

Overall, similar CEUS characteristics in inflammatory pseudotumors have been reported, including rapid WI followed by homogeneous enhancement and, different to our case, a slow WO with lesion enhancement exceeding that of surrounding tissue. Histopathological results in their study revealed sporadic necrosis and chronic inflammatory cell infiltration [19].

In comparison, the present case of pseudotumor and a patient diagnosed with adenocarcinoma were located at the same anatomical site (nictitating membrane) and presented with a similar mass effect on conventional ultrasound. Despite these similarities in location and ultrasonographic appearance, the underlying pathologies differed, with one being neoplastic and the other inflammatory. Notably, CEUS contrast behavior differed between the two lesions, and both diagnoses were confirmed histopathologically. The lymphohistiocytic pseudotumor demonstrated a predominantly homogeneous, centripetal enhancement pattern with progressively decreasing contrast intensity toward the center, without marked intralesional heterogeneity or clear early focal vascular irregularities. Furthermore, the lesion exhibited a rapid WI followed by a rapid WO.

In contrast, the nictitating membrane adenocarcinoma showed a more heterogeneous enhancement behavior, with initial enhancement of the surrounding tissue followed by early visualization of superficial tumor vessels. Enhancement within the lesion was irregular and centripetal, followed by a brief peak phase and earlier central wash‐out. Peripheral vessels remained visible for a longer duration, with intermittent centripetal filling. The adenocarcinoma also demonstrated a rapid WI, but in contrast to the pseudotumor, it showed a delayed WO. Overall, the CEUS findings in the present cases only partially corresponded to the differentiating features described in human medicine. While rapid WI was observed in both the pseudotumor and the adenocarcinoma, WO characteristics differed from the commonly described human pattern, with rapid WO in the pseudotumor and delayed WO in the adenocarcinoma. Thus, WI and WO characteristics alone did not differentiate inflammatory from neoplastic disease in these two cases according to the criteria described in human medicine [18, 19]. Instead, the observed differences in enhancement pattern and vascular architecture may provide additional information for differentiation.

Several factors may limit direct comparison with the human studies described above. Definitions and time thresholds used to categorize WI and WO as rapid, slow, or delayed may differ between studies, and differences in tumor biology and vascular architecture between human and veterinary patients may influence contrast enhancement behavior. Furthermore, the available studies describe CEUS characteristics of inflammatory pseudotumors, whereas specific CEUS characteristics of adenocarcinomas have not been reported [18, 19]. In addition, one study [18] assessed contrast kinetics using quantitative time‐intensity curve analysis, whereas the present study relied on qualitative assessment, which may have influenced the classification of WI and WO. Given these limitations and the small number of cases, these observations should be interpreted cautiously and require confirmation in larger prospective studies.

In human medicine, optic nerve lymphomas and meningiomas are considered particularly suitable for CEUS diagnostics due to their pronounced vascularization [16]. In the present study, both neoplasms were visualized with CEUS, which provided additional information on their enhancement characteristics. The centrifugal enhancement pattern in the lymphoma case was similar to that reported in canine and feline mediastinal lymphomas [28]. It is hypothesized that this reflects the lymph node‐like angioarchitecture of these tumors, with perfusion maintained by a centrally entering hilar vessel [28, 29]. While meningiomas have been proposed as suitable CEUS lesions due to their pronounced vascularization, their specific CEUS characteristics remain undescribed, highlighting the need for further investigation of this clinically relevant neoplasia.

Strong CEUS enhancement in inflammatory lesions is primarily attributed to inflammatory hyperemia and vasodilation, leading to increased regional perfusion. However, enhancement is not uniformly present across all inflammatory conditions [23]. To date, no studies have described the use of CEUS in inflammatory orbital or intraocular lesions. In the present study, variable degrees of contrast intensity were observed in inflammatory lesions, although a tendency toward stronger enhancement with a rapid WI and a delayed WO was noted by the authors. This is in line with the expected hyperemic response in actively inflamed tissue. The variability in enhancement may be explained by differences in the underlying pathophysiological stage and severity of inflammation, as well as the affected tissue type. Acute inflammatory processes with pronounced vasodilation are likely to exhibit stronger and more homogeneous enhancement, whereas more chronic or less active inflammatory conditions may show reduced or heterogeneous enhancement patterns due to vascular remodeling or tissue damage [23].

The observed enhancement of abscess capsules with sparing of the abscess content aligns with previous findings using contrast‐enhanced MRI [30, 31]. Dennis [11] reported an ocular abscess initially misdiagnosed as a neoplasm on conventional ultrasound, which was correctly identified by capsule enhancement on MRI. Two cases in this series demonstrated some degree of contrast uptake within the abscess, although the capsule typically showed stronger peripheral enhancement. Intralesional contrast enhancement may be attributed to vascularized septa within the abscess [32]. It is important to note that two abscesses in the included cases were undetectable by both B‐mode ultrasonography and CEUS, indicating that the advantages of CEUS over conventional B‐mode imaging should be interpreted cautiously for orbital abscesses.

Regarding myositis and steatitis, Fischer et al. [31] reported abnormal enhancement patterns and swelling using contrast‐enhanced MRI. In human medicine, CEUS has been shown to be more effective than conventional ultrasonography for diagnosing myositis due to its ability to quantify inflammation‐induced muscle hyperperfusion in acute cases [33, 34]. In this study, however, no consistent contrast enhancement characteristic was observed, suggesting that the additional diagnostic benefit of CEUS over B‐mode ultrasonography remains questionable for these lesions.

The limitations of this case series include its retrospective design and the fact that the operators were not blinded to the suspected diagnosis, which may have introduced potential bias. Additionally, varying contrast‐medium dosages and ultrasound probes were used. However, both dosages and probes used in this study provided satisfactory contrast enhancement. Most animals underwent CEUS without sedation, but in the sedated or anesthetized cases, cardiovascular alterations may have influenced perfusion.

The limited sample size precluded species‐specific analyses, which could be valuable in future studies evaluating conditions such as feline diffuse iris melanoma or FROMS. In some cases, histopathological confirmation was unavailable and the diagnosis was based solely on therapeutic response. Furthermore, many animals had multiple concurrent ophthalmic pathologies, which may have affected the CEUS findings.

Finally, quantitative analysis of time‐intensity curves was not performed, although Blohm et al. [15] have shown that qualitative and quantitative results can differ. Given that the primary goal of this investigation was to describe the practical applicability of CEUS, the study focused on qualitative assessment, acknowledging its inherent subjectivity. However, the reported time intervals (in seconds) in this study should be interpreted cautiously, as no formal quantitative time‐intensity curve analysis with region‐of‐interest‐based measurements was performed. The provided values are based on observational assessment of the recorded CEUS examinations and should be considered approximate reference points rather than precise quantitative measurements. Accordingly, they are intended primarily to complement the qualitative interpretation of contrast‐enhancement dynamics and to facilitate reader understanding and comparison between cases.

This study provides initial insights into the perfusion characteristics of various orbital and intraocular pathologies using CEUS. Further research is warranted to evaluate the potential of CEUS to differentiate or diagnose specific pathologies based on their enhancement characteristics.

Considering the higher costs of contrast agents and the need for specialized software, the additional diagnostic benefit of CEUS over B‐mode ultrasonography for assessing inflammatory lesions such as abscesses, uveitis, endophthalmitis, myositis and steatitis remains uncertain. In contrast, CEUS consistently detected persistent retinal perfusion in retinal detachments and demonstrated distinct enhancement characteristics in neoplastic lesions, likely reflecting tumor vascular characteristics, which may facilitate differentiation of neoplasia types in future clinical applications.

5. Conclusion

This case series highlights the utility of CEUS for visualizing a range of orbital and intraocular pathologies. In neoplastic lesions, CEUS provides distinct enhancement characteristics, aids in precise localization, and demonstrates tissue perfusion characteristics. These features may facilitate more accurate differentiation of pathologies, supporting the role of CEUS as a valuable adjunct to conventional ophthalmic ultrasonography.

Author Contributions

Janneke I. Ortner: conceptualization, writing – original draft, data curation, formal analysis. Katharina M. Hittmair: conceptualization, data curation, supervision, writing – review and editing. Barbara Nell: conceptualization, supervision, writing – review and editing. Klaas‐Ole Blohm: conceptualization, writing – review and editing, data curation, supervision.

Disclosure

The authors have not used AI to generate any part of the manuscript.

Ethics Statement

The owners provided written consent for the publication of patient data for research purposes.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.