Posterior Segment Manifestations of Cat-scratch Disease: A Mini-review of the Clinical and Multi-modal Imaging Features

ABSTRACT

Bartonella henselae, an intracellular gram-negative bacillus, is usually transmitted from infected cats to humans by direct or indirect contact. The bacterium mainly infects erythrocytes and endothelial cells thereby leading to so called cat-scratch disease (CSD) and may present with various localised and/or systemic manifestations. The eye is the most commonly affected organ in disseminated CSD and ocular bartonellosis has been reported in 5–10% of CSD patients. The most well-known clinical feature of ocular bartonellosis is neuroretinitis but various sight-threatening posterior segment lesions involving the optic nerve, retinal vasculature, retinal and choroidal tissues may occur during the disease course. This mini-review aims to overview both the clinical and multi-modal imaging characteristics of posterior ocular segment manifestations of CSD.

Introduction

Cat-scratch disease (CSD) is a common zoonotic illness seen widespread in the world and is usually a self-limiting disease. It was first described in 1889 by Parinaud in patients with chronic fever, regional lymphadenopathy, and follicular conjunctivitis.¹ The relationship between cats and CSD was described in 1931 by Debré.¹ More than half a century later, Bartonella henselae (formerly known as Rochalimaea henselae) was identified as the causative agent in 1992.¹ Bartonella henselae is a fastidious, small intracellular gram-negative bacillus that mainly infects erythrocytes and endothelial cells.^2–4 Cats are the natural reservoir for the bacterium⁵ and 10–40% of cats are thought to be infected with it.⁴ The bacterium is usually transmitted to humans directly through bites, scratches, or licks.^2,5,6 Although cat fleas (Ctenocephalides felis) have been held responsible for cat-to-cat transmission, their role in cat-to-human transmission is still debatable.^1,6 In addition, the transmission of the infection from person-to-person remains unclear.⁶ However, recent studies suggest that the bacteria can be transmitted via transfusion of blood products.⁷ Although epidemiological studies have reported a history of a cat bite or scratch in 60% of cases and contact with a cat is present in about 90% of cases,⁸ a history of contact with a cat cannot be detected in some patients with ocular CSD.⁴ The mean annual incidence is 4.5 per 100.000 population according to the US Centers for Disease Prevention and Control⁹ and Bartonella henselae seroprevalence has been reported to range between 2 to 32%.² The disease usually occurs in children and adolescents.^2,5 CSD is also described as a seasonal illness that peaks during the winter and autumn with a decrease in spring.¹⁰ As CSD can occur in both immunocompromised and immunocompetent patients, immunity status of the host and pathogen-related factors seems to determine the severity of systemic and ocular manifestations.^3,6,11 While immunocompetent patients with CSD develop focal granulomas characterised by a necrotic area surrounded by histiocytes, lymphocytes and giant cells, a vasoproliferative type response can be seen in immunocompromised patients. This response is an indicator for the interaction between the bacterium and vascular endothelial cells.² The clinical presentation of CSD is considered typical in 90% of affected cases and the disease usually starts with a non-pruritic erythematous papule or pustule at the primary cutaneous inoculation site. The cutaneous lesion usually lasts for around 3 to 10 days but may remain for up to 2 to 3 weeks.^1,4,12 Regional lymphadenopathy can be detected within 1 to 2 weeks following the cutaneous lesions and usually affects the epitrochlear, axillary, and cervical lymph nodes. Lymphadenopathy may be painful and suppurative and can affects a single node in a unilateral fashion in half of the cases.^1,2,4 While cervical lymph node involvement is more evident in patients younger than 15 years of age, inguinal or axillary lymph node involvement is more common in patients older than 15 years of age.¹³ Systemic symptoms and signs, such as low-grade fever, fatigue, headache, chills, nausea, vomiting, sore throat, and night sweats may also be present.^1,4,6 The disease is self-limiting in most of the patients and improves within months.⁶ On the other hand, the so-called atypical CSD begins with extra-nodal manifestations that is the consequence of haematogenous spread of bacteria in the remaining 10% of cases.¹ Encephalopathy, aseptic meningitis, pneumonia, pleural effusion, endocarditis, arthritis, osteomyelitis, paravertebral abscesses, hepatosplenic disease (granulomatous hepatitis, hepatic and splenic abscess, splenomegaly) are among the reported severe extra-ocular systemic manifestations.^4,12 The eye is considered to be the most frequently affected organ in the circumstance of haematogenous spread of the bacterium and ocular manifestations have been reported in 5 to 10% of cases with CSD.^1,4,9 Adnexal (Parinaud oculo-glandular syndrome), vitreal, retinal vascular, retinal/choroidal tissue, macular and optic nerve involvement are among the reported CSD-related ocular manifestations.^3–6,11,12 In this manuscript, we aim to overview the clinical and multi-modal imaging characteristics of posterior ocular segment manifestations in patients with CSD.

Methods

A meticulous literature search was performed between 1990–2020 by using the keywords ‘’Bartonella henselae’’, ‘‘cat scratch disease’’, ‘‘fluorescein angiography (FA)’’, ‘‘neuroretinitis’’, ‘‘ocular bartonellosis’’, ‘‘optical coherence tomography (OCT)’’ and ‘‘OCT-angiography (OCT-A)’’ to find out the related studies on clinical and multimodal imaging characteristics of posterior ocular segment involvement in CSD.

Posterior segment manifestations of cat-scratch disease

Posterior segment manifestations of CSD will be discussed under the subtitles of neuroretinitis, retinal vascular involvement, retinal and choroidal whitish lesions, macular involvement and others. These are briefly summarised in Table 1.^1–50

Table 1.

Posterior segment manifestations of cat-scratch disease

Vitreous manifestations	Intermediate uveitis, vitreous haemorrhage, acute endophthalmitis
Optic nerve manifestations	Neuroretinitis, optic disc oedema, optic nerve head granuloma, peri-papillary choroidal neovascularisation, papillitis, and optic disc neovascularisation
Retinal vascular manifestations	Retinal vasculitis, angiomatous-like proliferation, branch or central retinal artery occlusion, branch or central retinal vein occlusion
Retinal/choroidal tissue manifestations	Retinal infiltrate, acute multi-focal inner retinitis, chorioretinitis, serpiginous-like choroiditis, helioid unifocal choroiditis, and retinal neovascularisation
Macular manifestations	Serous macular detachment, macular star, cystoid macular oedema, macular hole, macular neovascularisation

Neuroretinitis

Neuroretinitis, a specific form of optic neuropathy, is characterised by the inflammation of the optic nerve and peri-papillary retina with subsequent formation of a macular star.^6,14 Of note, CSD is the most common infectious cause of neuroretinitis.¹⁵ Ocular symptoms usually commence 2 to 3 weeks after the onset of systemic symptoms and the patients usually complain of painless vision loss accompanied by a relative afferent pupillary defect, visual field defects (central, caeco-central, or para-central scotoma, or an enlarged blind spot), and dyschromatopsia.^2,6 Visual acuity varies between 20/20 and light perception on presentation.⁶ In a well-known review on neuroretinitis, Purvin et al.¹⁴ reported the outcomes of 65 previously published cases (only four were bilateral) and the initial visual acuity was 20/40 or better in 14.5% of the eyes, between 20/50 and 20/200 in 33.3%, and under 20/200 in 52.2%.¹⁴ CSD-related neuroretinitis usually presents unilaterally but sometimes bilateral involvement may occur, regardless of the immune status of the host.⁶ In a case series by Wilner et al.,¹⁵ unilateral involvement was reported in six of seven patients (85%) with CSD neuroretinitis. Mild vitritis, optic disc swelling, and partial or complete star-like exudates extending from the optic disc to the fovea are among its typical findings.^9,12 A macular star is characterised by the so-called stellate pattern exudates and caused by the leakage of lipid-rich exudates due to increased permeability of the optic nerve head capillaries. It generally develops after the resolution of the accompanying fluid.¹⁶ A macular star may not be present on presentation and often develops within 2 weeks after the onset of optic disc oedema. Optic disc oedema usually wanes within 2 weeks, but complete resolution may take up to 3 months. Concurrently, the macular star usually resolves within a month, but still can be detected for up to a year.⁹ The optic disc oedema is often accompanied by papillary and peri-papillary telangiectatic vessels in CSD-related neuroretinitis and is associated with peri-papillary retinal thickening and adjacent serous retinal detachment. In addition, intra-retinal haemorrhages may occur. A significant angiomatous lesion at the peri-papillary area or on the optic disc, mimicking even a mass or toxocariasis, may also develop.⁶ Neuroretinitis is not a pathognomonic finding for CSD and its differential diagnosis includes infectious (Lyme, tuberculosis, syphilis, leptospirosis, toxoplasmosis, toxocariasis), systemic (diabetes mellitus, malignant hypertension, sarcoidosis, Behçet’s disease), and neurological causes (intracranial hypertension).^4,17 Though the diagnosis of neuroretinitis can be made clinically, systemic investigations including serological tests and multi-modal imaging techniques including fundus autofluorescence (FAF), FA, indocyanine green angiography (ICGA), OCT, and OCT-A may be necessary. FA exhibits the presence of papillary and peri-papillary telangiectasia in the early phase and optic disc leakage in the late phases but with no no peri-foveal capillary leakage.^6,15,18–20 Similarly, ICGA demonstrates optic disc hyper-cyanescence without associated choroidal involvement.^6,20 Macular exudates are seen as star-shaped hypo-autofluorescent lesions on FAF images due to blockage of the autofluorescence.²¹ Subtle retinal findings such as sub-retinal fluid and retinal thickening may get unnoticed ophthalmoscopically but are easily detected with the help of OCT. Multiple hyper-reflective foci at the outer plexiform layer corresponding to the hard exudates, flattening of foveal contour, sub-retinal fluid, and neuro-sensorial retinal thickening have been described as the OCT findings of the disease.^2,15,22 Sub-retinal fluid was present in all eight eyes featuring CSD associated neuroretinitis on OCT in a previous study by Habot-Wilner et al.¹⁵ They stated that OCT could demonstrate not only the presence of sub-retinal fluid but also its height and likely duration and thereby help the clinicians to estimate how long treatment would be needed for. They also added that coexistent sub-retinal fluid might be harmful to the photoreceptors.¹⁵ Epi-papillary vitreous infiltrates can be the earliest OCT sign of neuroretinitis and are the conglomerates of inflammatory cells located in the posterior vitreous adjacent to the optic nerve head. They often occur prior to macular star formation. This finding is not observed in other conditions associated with optic disc oedema such as anterior ischaemic optic neuropathy or papilloedema.^22,23 OCT also elucidates the presence of inner retinal folds in association with neuroretinitis that may appear due to mechanical effect of the retinal oedema. These folds consist of outwardly expanding concentric rings that can even reach out to the macula and this pattern is different from the folds observed in other causes of optic disc oedema.^22,23 OCT-A is a non-invasive imaging technique that can provide qualitative and quantitative data on the retinal and choroidal circulation without injection of a dye.^24,25 Bartonella henselae affects the vascular endothelial cells by inducing endothelitis and consequently angio-proliferative lesions may occur. Thus, OCT-A evaluation of the retinal and choroidal vascular layers may yield additional information.^22,27 However, there is only limited literature on OCT-A findings associated with CSD neuroretinitis. Mason et al.²⁶ described the OCT-A findings of a 20-year-old man with CSD neuroretinitis who had retinal and optic disc neovascularisation without any retinal vascular occlusion. Peri-papillary telengiectatic vessels can also be detected by OCT-A in patients with CSD neuroretinitis.⁶

The multi-modal imaging features and the disease course of a 19-year-old woman with unilateral neuroretinitis secondary to CSD is illustrated in Figures 1 and Figure 2.

Figure 1.

The right eye of a 19-year-old woman with cat-scratch disease related neuroretinitis at the time of presentation (Bartonella henselae IgG titres, 1:320). Colour fundus photograph (A) showing mild optic disc oedema and a prominent macular star. Fundus autofluorescence image (B) revealing the star-shaped hypo-autofluorescent lesions. Fundus angiogram (C,D) illustrating late leakage from the optic disc. En-face optical coherence tomography (OCT) images: the superficial layer is almost normal (E); the deep layer shows marked hyper-reflective dots (F); outer retina (G); and choriocapillaris layers (H) illustrate hypo-reflective star forming dark dots. OCT-angiography images of the superficial (I) and deep (J) layers displaying an almost normal appearance, but the outer retina (K) and choriocapillaris layers (L) show star-shaped non-detectable flow signal areas secondary to shadowing artefacts. OCT image (M) revealing multiple hyper-reflective foci at the outer plexiform layer corresponding to the retinal exudates with or without posterior shadowing

Figure 2.

The case from Figures 1, 6 weeks after the initial presentation (After an oral azithromycin and trimethoprim-sulfamethoxazole combination). Colour fundus photograph (A) revealing improvement in optic disc oedema and macular star. Optical coherence tomography (OCT) image (B) showing residual multiple hyper-reflective foci at the outer plexiform layer with or without posterior shadowing. OCT-angiography images (C-F) displaying the significant improvement in the areas of non-detectable flow signal in parallel to the partial resolution of the macular star

Retinal vascular manifestations

CSD can present with various retinal vascular changes. Branch retinal artery or vein occlusion (predominantly arteriolar occlusion) may sometimes be seen in patients with ocular CSD, with or without neuroretinitis, whereas central retinal vein and/or artery occlusion has rarely been reported.^15,28–32 The retinal vascular occlusion rate varies between 7 and 23% and it can sometimes be the only sign of CSD.^4,15,17,31 Thus, young patients with branch retinal artery occlusion should be investigated for associated CSD when there is no obvious standard risk factors for the retinal vascular occlusion.^12,15 These patients usually present with decreased visual acuity and/or visual field defects. Naturally, the severity of the visual disturbance depends on the proximity of the affected vessel to the macula.⁴ Direct mechanical compression on the vessels by the focus of retinitis or oedematous optic nerve has been blamed in the pathogenesis of vascular occlusion. Thrombogenic mediators triggered by the bacteria may contribute to vascular endothelial damage and may also play a role in arterial occlusion (obliterative or thrombogenic vasculitis).^15,28–32

Retinal and choroidal whitish lesions

The rate of retinal or choroidal whitish lesions has been reported to be between 7 and 83% in cases of CSD.^4,12,17,31 In a study conducted by Solley et al.,³¹ retinal and/or choroidal white lesions were reported as the most common posterior manifestation in CSD (29 of 35 eyes, 83%). They stated that these white lesions had various dimensions and could be located in the deep retina (49%), superficial retina (30%), full-thickness retina (14%), and the choroid (7%).³¹ In another study by Tolou et al.,³³ focal chorioretinitis was present in eight of 12 patients (67%) with CSD. These lesions looked hypo-fluorescent in the early phases of FA and demonstrated centripetal hyper-fluorescence in the late phases. Additionally, the authors described the ICGA features in a patient where chorioretinal foci displayed marked hypo-cyanescence both in the early and late phases of the angiogram.³³ CSD-associated superficial retinal infiltrates may resemble cotton-wool exudates. Although the underlying mechanism of retinal infiltrations is not fully understood it is thought to occur due to focal arteriolar occlusion related ischaemia.⁴ These superficial retinal infiltrates exhibit central hypo-fluorescence with surrounding hyper-fluorescence on FA. These infiltrates can be visualised as focal hyper-reflective spots in the inner retinal layer on OCT. The differential diagnosis of retinal infiltrates includes several posterior uveitis entities such as Behçet’s disease and ocular toxoplasmosis. While diffuse vitritis is common in Behçet’s disease, vitreous cells are often not apparent over the retinal infiltrates in CSD patients. Toxoplasma retinochoroiditis presents with localised choroidal thickening under the retinal lesion and is accompanied by inflammatory cells in the posterior hyaloid neighbouring the retinal lesion unlike CSD. Even though CSD-associated superficial retinal infiltrates do not cause any clinical symptoms they should be monitored closely as they may cause retinal vascular occlusions.⁴ Acute multi-focal retinitis (AMR) is a rare clinical presentation of CSD and is characterised by multiple small or medium-sized superficial retinal infiltrates in the retina. Eight of 35 patients with AMR (22.8%) were found to have CSD in a study by Khochtali et al.³⁴ Twenty-four patients had Rickettsia infection (68.5%) and one patient had syphilis (2.9%) in their series. These lesions exhibited slight hypo-fluorescence or iso-fluorescence in the early phases and showed staining in the late phases of FA. There was also focal hyper-reflectivity and thickening of the inner retinal layers with or without posterior shadowing on OCT. AMR is usually self-limiting and the lesions often disappear completely within 3 to 12 weeks, without any scarring and with a good visual outcome.³⁴ Pichi et al.²⁷ presented the multi-modal imaging characteristics of a 14-year-old male with a white focal chorioretinal lesion along the inferior arcade accompanied by a macular star. They noticed anomalous vessels on the surface of the infectious focus ophthalmoscopically and early hyper-fluorescence of the lesion’s borders with late pooling on FA. OCT documented a hyper-reflective inner retinal lesion and sub-retinal fluid associated with back-shadowing. OCT-A demonstrated that the anomalous vessels had a central intralesional feeder vessel and that they were tortuous and fragmented with circumferential anastomoses at the level of deep capillary plexus.²⁷

Macular manifestations

Cystoid macular oedema (CME) and macular holes can occur in patients with CSD. Manousaridis et al.,³⁵ reported a 35-year-old woman with CSD-related macular oedema accompanied by mild optic disc oedema and a focus of retinochoroiditis close to the lower temporal vascular arcade without any sign of vasculitis and vitritis. FA revealed typical CME with petaloid hyper-fluorescence together with early hypo-fluorescence and late hyper-fluorescence corresponding to the retinochoroiditic area. Complete resolution of the macular oedema and improvement in visual acuity was achieved successfully following a single-dose of intravitreal ranibizumab.³⁵ Macular holes secondary to CSD have been reported in five patients so far.^36–40 In four of these patients, neuroretinitis was also present^36,37,39,40 and the macular holes developed within 1 to 2 months following onset of the disease.^36–38,40 However, Seth et al.³⁹ reported a full-thickness macular hole at the first eye examination in an 11-year-old girl with CSD neuroretinitis and then the hole enlarged during follow-up. The mechanisms behind macular hole formation following CSD neuroretinitis include progressive pre-macular vitreous liquefaction and contraction, tangential forces by epiretinal membrane formation, and intraretinal weakening secondary to inflammation or CME.^39,40 Interestingly, Gunzenhauser et al.⁴⁰ described an 11-year old boy with a spontaneously closing full-thickness macular hole within 6 months after presentation with CSD neuroretinitis. Thus, macular holes in eyes with CSD should not be operated on in a hurry as spontaneous hole closure can occur in inflammatory conditions.⁴⁰ In a case report by Robert et al.,⁴¹ unilateral choroidal neovascularisation (CNV) was reported in a 37-year-old woman with positive Bartonella henselae serology. There was a small extra-foveal serous retinal detachment together with an area of yellow-white exudation within the papillomacular bundle. The lesion was characterised as having early lacy hyper-fluorescence and late leakage on FA. OCT demonstrated intraretinal and subretinal thickening together with signs of exudation. Although the relationship between Bartonella henselae and CNV could not be fully elucidated the authors suggested that Bartonella henselae should be considered in the differential diagnosis of idiopathic CNV.⁴¹

Other posterior segment manifestations

CSD patients may also present with optic disc granulomas and peri-papillary angiomatous lesions that may result in vision loss in the affected eyes.⁴² CSD-related granulomas may mimic retinoblastoma or toxocara granuloma.s^43,43 Aziz et al.⁴² reported a 7-year-old boy presenting with an optic disc granuloma, concurrent exudative retinal detachment and vitreous seeding. Sayyad et al.⁴³ reported an 8-year-old girl who was examined due to vision loss together with leukocoria. There was a posterior granulomatous looking mass with an exudative retinal detachment imitating a Toxocara granuloma but detailed systemic work up proved the Bartonella henselae infection.⁴³ Gray et al.⁴⁴ described a peri-papillary angiomatous lesion and branch retinal artery occlusion in a 20-year-old man with CSD neuroretinitis and the lesion looked like a vascular mass involving the optic disc. FA demonstrated intense hyper-fluorescence and late staining of the lesion. Latanza et al.⁴⁵ described peri-papillary CNV in an 8-year-old girl with CSD neuroretinitis during the primary infection. They reported an early roundish hyper-fluorescent lesion with late leakage at the peri-papillary region on FA and there was associated serous retinal detachment on OCT. They suggested that CSD can be considered among the causes of inflammatory CNV.⁴⁵ Portero et al.⁴⁶ reported a 36-year-old man with unilateral serpiginous-like choroiditis secondary to CSD. The lesions exhibited early fluorescein blockage but there was progressive leakage and staining at the later phases. Curi et al.⁴⁷ reported a helioid unifocal choroiditis in a 30-year-old HIV-positive patient with CSD. The yellowish chorioretinal lesion was surrounded with haemorrhages and fluid accumulation on FA and resembled an angiomatous lesion.⁴⁷ In another study conducted by Curi et al.⁴⁸ on ocular manifestations in three HIV-positive patients with CSD, there were yellowish subretinal masses in all three patients. While FA showed abnormal vascular networks corresponding to the lesions, ICGA revealed early diffuse choroidal hyper-cyanescence, but the abnormal vascular networks looked less evident than their appearance on FA.⁴⁸

Multi-modal imaging features of a 36-year-old woman with a unilateral CSD-related peri-papillary granuloma at presentation and two weeks after treatment with oral azithromycin and trimethoprim-sulfamethoxazole are shown in Figures 3 and Figure 4, respectively.

Figure 3.

A 36-year-old woman with a left peri-papillary granuloma secondary to cat-scratch disease at the time of presentation (Bartonella henselae IgG titres > 1:320). Colour fundus photograph (A) showing telangiectatic vessels at the temporal aspect of the optic disc accompanied by a flame-shaped haemorrhage and peri-papillary whitish area corresponding to the granuloma. Fundus autofluorescence image (B) displaying a peri-papillary well-demarcated hypo-autofluorescent area. Fundus angiogram (C,D) showing late hyper-fluorescence of the granuloma. Optical coherence tomography (OCT) (E) demonstrating the peri-papillary subretinal fluid and inner retinal thickening. OCT-angiography images of superficial (F), deep (G), outer retina (H), and choriocapillaris (I) slabs illustrating the non-detectable flow signal areas probably secondary to shadowing artefact

Figure 4.

Colour fundus photograph, optical coherence tomography (OCT), and OCT-angiography (OCT-A) images of the patient in Figures 3, Figure 2 weeks later. Colour fundus photograph (A) showing the significant improvement of the peri-papillary lesion. OCT image (B) of the peri-papillary area showing a prominent decrease in retinal thickening and subretinal fluid amount. OCT-A images of superficial (C), deep (D), outer retina (E), and choriocapillaris (F) slabs depicting the reduction in non-detectable flow signal areas secondary to shadowing artefact in parallel to the decreased inner retinal oedema and subretinal fluid

Diagnosis and laboratory testing

The diagnosis of CSD is made mostly by a compatible history together with a typical clinical presentation (young age, a history of cat-related trauma or contact with a cat, systemic symptoms and typical neuroretinitis, etc.) and laboratory tests.⁶ Blood culture, skin testing, lymph node biopsy, serological tests (indirect fluorescent antibody assay [IFA] or enzyme-linked immunosorbent assay [ELISA]), and polymerase chain reaction (PCR) are among the confirmatory tests performed in patients with likely CSD.^6,12 The most commonly used test is serological investigation for Bartonella henselea immunoglobulin (Ig) M and IgG titres.^6,49 However, the sensitivity and specificity of these tests are variable. IFA is the most widely preferred diagnostic test in immunocompetent patients over ELISA as its sensitivity and specificity is 90% and ELISA gives more false negatives.^11,12 IgM positivity against Bartonella henselae implies an acute or very recent infection and confirms the CSD diagnosis. When IgM is negative, it is controversial to diagnose CSD with a single IgG measurement due to the high rate of positive serology in the normal population.⁴⁸ Therefore, consecutive measurements of IgG titres may be required in the convalescent period and an increase in IgG titres during this period may help to confirm the diagnosis. In addition, IgG and IgM detected in the serological tests are time-sensitive. While IgM cannot be detected after the third month of infection, IgG can only be detected in 25% of patients in the first year.^12,49 However, IgG titres can guide the clinician in assessing the disease stage. Titres of 1:64 or less may be suggestive of no active infection, while titres of 1:256 and above confirms acute infection. However, titres between 1:64 and 1:256 suggest possible CSD, which requires retesting after 10 days.^11,12,49 PCR is another test that can be used for diagnosis and is usually used when the serology is negative. It can also distinguish between Bartonella species. PCR has a higher specificity but less sensitivity than serological testing.

Treatment

There is no consensus or generally accepted algorithm for the treatment of CSD. However, the age of the patient, host immunity and the type of clinical manifestation are the key factors in deciding on treatment.^6,11 Mild to moderate systemic CSD may not require any treatment in immunocompetent patients as CSD is mostly self-limiting disease. On the other hand, severe systemic or ocular CSD manifestations in otherwise healthy subjects or any presentations in immunocompromised patients should be treated with systemic antibiotics.⁶ The best treatment option for posterior segment involvement is still under debate. Doxycycline, rifampicin, macrolides (erythromycin, clarithromycin, azithromycin), trimethoprim-sulfamethoxazole, quinolones, ceftriaxone, aminoglycosides, alone or in combination, are among the treatment alternatives.^4,6,11,50 The most preferred antibiotic is doxycycline (100 mg, twice per day) and the recommended treatment duration is 4 to 6 weeks in immunocompetent patients, but longer administration (up to 4 months) is required to prevent recurrences in immunocompromised patients.^2,11 Macrolides are mostly preferred in children under 12 years of age because of the side effects of doxycycline.^2,11 Paradoxical responses to antibiotics are possible in patients with ocular CSD. Therefore, oral corticosteroids may be combined with antibiotics in patients with ocular CSD associated with a severe inflammatory response.⁶ Wilner et al.¹ reported that visual outcomes were better in patients treated with a corticosteroid and antibiotic combination than in patients treated solely with antibiotics in a very recent study.¹

On the other hand, choroidal neovascularisation and CME secondary to Bartonella infections can be treated intravitreally with anti-vascular endothelial growth factor agent administration alongside systemic antibiotic therapy in selected patients.^11,45

Conclusion

CSD may present with a wide range of posterior segment ocular manifestations involving the optic nerve, retinal vasculature, retinal and choroidal tissue as summarised above and may cause a multitude of lesions that can mimic several other posterior segment diseases associated with vascular, inflammatory, neoplastic or infectious causes. Multi-modal imaging techniques including FAF, FA and ICGA, OCT and OCT-A can be utilised in the diagnosis and follow up of the patients with the posterior segment involvement. OCT-A findings of CSD lesions are relatively less-known when compared with ancillary tests such as FA and OCT but knowledge about OCT-A is accumulating. Though the diagnosis of CSD with posterior segment eye disease can be made by a careful history taking, clinical and imaging examination, laboratory confirmation is sought in most cases. An accurate diagnosis will prevent unnecessary treatment as the anatomical and visual prognosis is generally good in ocular CSD.

Declaration of interest statement

Ethical issues have been completely observed by the authors. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship in this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published. No conflict of interest has been presented.