Kyrieleis plaques are multiple segmental yellowish-white lesions arranged in a beaded pattern along the retinal arteries. They are also called segmental retinal arteritis (SRA).
First reported in 1933 by Werner Kyrieleis in a presumed case of tuberculous uveitis. Alternative names include Kyrieleis vasculitis, Kyrieleis arteriolitis, nodular periarteritis, and segmental retinal periarteritis.
The deposits are reversible lesions located within the arterial wall, not in the lumen or outside the vessel. They always reflect severe intraocular inflammation and have been reported in both infectious and non-infectious inflammatory posterior uveitis. Although rare, it is suggested that they may be hidden by vitreitis and often missed.
The most common cause is toxoplasmic retinochoroiditis (ocular toxoplasmosis). 2, 3)
The classification of associated underlying diseases is shown below.
Infectious causes
Toxoplasma: Most common. Reported even in atypical cases of ocular toxoplasmosis. 2, 3)
HSV-1/HSV-2: Causative viruses of acute retinal necrosis (ARN). Can also occur in acute retinal necrosis after encephalitis. 1, 3)
VZV: Main causative virus of acute retinal necrosis. 1, 3)
Others: CMV, tuberculosis, syphilis, Rickettsia conorii (Mediterranean spotted fever), etc. 3)
Non-infectious causes
Behçet’s disease: an inflammatory disease with systemic vasculitis.
Sarcoidosis: a granulomatous inflammatory disease.
Brolucizumab-associated retinal vasculitis: a new drug-related cause reported as a side effect of anti-VEGF drugs. 3)
Clinically, it is considered a rare finding, but it has also been pointed out that it may be missed due to being hidden behind severe vitritis. Since it may only be confirmed after vitritis subsides, it is important to actively examine the fundus during follow-up of intraocular inflammation. 1, 2)
Kyrieleis plaques themselves do not cause specific subjective symptoms. Symptoms are mainly due to intraocular inflammation from the underlying disease.
Typical symptoms are as follows:
In reported cases, a patient with acute retinal necrosis (secondary to HSV-1 encephalitis) presented with blurred vision, redness, and floaters for 3 days. 1) In an atypical ocular toxoplasmosis (OT) case, only left eye redness for 3 days was noted, with visual acuity preserved at 6/9. 2) In a multifocal segmental retinal arteritis (OT) case, painful redness for 2 weeks was reported, with visual acuity dropping to hand motion (HM). 3)
In the fundus, a characteristic pattern of segmental yellowish-white deposits along the retinal arteries appears like a string of beads. They have a shiny, calcified appearance.
The main features of the findings are shown below.
The timing of appearance and resolution of Kyrieleis plaques in each disease is shown below.
| Underlying disease | Time of appearance | Time of resolution |
|---|---|---|
| Acute retinal necrosis (HSV-1)1) | 2 weeks after treatment initiation | Resolves in 3 months |
| OT (atypical)2) | 4 weeks after treatment initiation | Resolves in 2 months |
| OT (multifocal) 3) | At diagnosis | Resolves in 5 weeks |
Differentiation is important because they appear similar. Kyrieleis plaques involve only arteries, show no leakage on FA, and do not extend beyond the vessel wall. In contrast, frost-branch angiitis involves both arteries and veins, shows clear leakage on FA, and extends beyond the vessel wall. 3)
The etiology of Kyrieleis plaques is not fully understood, but they always occur in association with severe intraocular inflammation.
Infectious causes are the most common, with ocular toxoplasmosis being the most frequent. 2, 3) In acute retinal necrosis (ARN), HSV-1, HSV-2, and VZV are causative, and cases of acute retinal necrosis secondary to herpes encephalitis have been reported. 1, 3) Other causes include CMV, tuberculosis, syphilis, and Rickettsia conorii (Mediterranean spotted fever). 3)
Non-infectious causes include Behçet’s disease, sarcoidosis, and brolucizumab (anti-VEGF drug)-associated retinal vasculitis. 3)
Major risk factors are as follows:
Diagnosis of Kyrieleis plaques is primarily clinical, and dilated fundus examination is essential. Combining various imaging tests allows evaluation of the lesion characteristics and underlying disease.
Fluorescein Angiography (FA)
Most important differential point: No vascular leakage is observed in the lesion area. This indicates that inflammation is confined to the arterial endothelium. 1, 2, 3)
Arterial filling: Maintained normally. No occlusive changes.
Report by Pichi et al.: Early hypofluorescence and late hyperfluorescence without leakage.
ICG Angiography
Sensitivity: Considered the most sensitive test.
Mechanism: Amphiphilic ICG molecules bind to inflammatory molecules.
Findings: Well-defined hyperfluorescence throughout all phases.
OCT / OCTA
Serological tests to confirm the underlying disease are also essential.
A comparison of findings with major differential diagnoses is shown below.
| Differential diagnosis | Vessels involved | FA leakage |
|---|---|---|
| Kyrieleis plaques | Arteries only | None |
| Frosted branch angiitis | Arteries + veins | Present |
| Retinal embolism | Artery only | None (occlusion present) |
The absence of FA leakage indicates that inflammation does not involve the full thickness of the vessel wall but is limited to the arterial endothelium. In full-thickness inflammation (vasculitis), vascular permeability increases, causing FA leakage; however, in Kyrieleis plaques, there is no leakage, suggesting the lesion is confined to the endothelium. Based on this finding, Pichi et al. proposed the term “endothelitis.” 1)
There is no specific treatment for Kyrieleis plaques themselves. The primary goal is to treat the underlying disease, and the plaques resolve with control of intraocular inflammation.
The main treatment regimens by underlying disease are shown below.
| Underlying disease | Antimicrobial agent | Steroid |
|---|---|---|
| OT (standard) 2) | SMX-TMP 800/160 mg/day × 8 weeks | PSL 1 mg/kg/day (added after 48 hours) |
| OT (Swedish standard) 3) | AZM 500 mg/day × 5 weeks | PSL 1 mg/kg/day → taper over 10 days |
| Acute retinal necrosis1) | Intravitreal foscarnet + IV ACV → oral VAL | PSL 1 mg/kg/day (added after 36 hours) |
The classic triple therapy is pyrimethamine + sulfadiazine + steroids for 4–6 weeks.2)
Two alternative regimens are now widely used:
In a report of Kyrieleis plaques secondary to acute retinal necrosis, the following regimen was administered.1)
Kyrieleis plaques themselves are benign findings and do not directly lead to worsening of visual prognosis. 2) With appropriate treatment, they resolve without sequelae. The resolution period is approximately 2 to 3 months.
Kyrieleis plaques themselves are not thought to directly worsen visual prognosis. 2) Visual prognosis is influenced by the severity of the underlying disease (toxoplasmosis, acute retinal necrosis, etc.) and the appropriateness of treatment. With proper treatment, Kyrieleis plaques resolve without leaving sequelae.
The composition and exact localization of the deposits in Kyrieleis plaques have not yet been fully elucidated.
Historically, the following hypotheses have been proposed.
The current prevailing interpretation is that Kyrieleis plaques result from the deposition of immune cells and inflammatory debris within the arterial vessel wall. 1) Since no FA leakage is observed, it is presumed that inflammation is not full-thickness but limited to the endothelium, without increased vascular permeability. 1, 2, 3)
The pattern of Kyrieleis plaques in acute retinal necrosis is characteristic. They may appear only after the inflammation subsides following treatment initiation. 1) On the other hand, some cases are already confirmed at the time of diagnosis; in the report by Makri et al., 3 out of 8 cases were observed at diagnosis. 1)
A multimodal imaging study by Pichi et al. (2017) included 25 eyes and performed comprehensive analysis combining FA, ICG, FAF, OCT, and OCTA. This showed that ICG angiography is the most sensitive test and that the pathology may be an endothelium-limited inflammation that should be called “endothelitis.” 1)
In vivo evaluation by OCT angiography (OCTA) demonstrated narrowing of intraluminal blood flow signals at the site of Kyrieleis plaques (Tsui et al.). It is expected to be applied as a non-invasive tool for assessing disease activity.
In recent years, cases of Kyrieleis arteritis occurring after administration of brolucizumab (anti-VEGF drug) have been reported, drawing new attention as a drug-induced cause. 3)
Regarding Kyrieleis plaques, case reports and small case series still constitute the main body of research, and the establishment of standardized diagnostic and reporting criteria remains a future challenge. Further elucidation of the pathology and establishment of optimal treatment regimens for each underlying disease are needed.
Makri OE, Tsekouras IK, Leonidou L, Kagkelaris K, Kozobolis V, Georgakopoulos CD. Kyrieleis arteriolitis associated with acute retinal necrosis due to herpes simplex virus type 1 secondary to herpetic encephalitis. Vision. 2022;6(2):27.
Teng Siew T, Mohamad S, Sudarno R, Md Said H. Atypical ocular toxoplasmosis with remote vasculitis and Kyrieleis plaques. Cureus. 2024;16(1):e52756.
Khadamy J. Atypical ocular toxoplasmosis: multifocal segmental retinal arteritis (Kyrieleis arteritis) and peripheral choroidal lesion. Cureus. 2023;15(10):e47060.
Tadepalli A et al. Kyrieleis plaques: recognising a rare presentation of ocular inflammation. Clin Exp Optom. 2024;107(8):863-865.
Amato VS et al. Recurrent acquired ocular toxoplasmosis associated with Kyrieleis plaques and documented allergy to sulfonamide. Diagn Microbiol Infect Dis. 2024;109(3):116266.
