Lemierre’s Syndrome was first described in 1936 by Andre Lemierre, who published 20 cases of anaerobic septicemia and septic thrombophlebitis that lead to the death of 18 patients, while in the pre-antibiotic era 3,4. It is a life-threatening condition that most commonly affects previously healthy young adults. It is characterized by head/neck bacterial infection, classically originating from pharyngitis, but it has also been described following dental infections, sinusitis, cellulitis, septic thrombosis of cavernous sinus. Thrombosis of the IJV with septic embolic complications in a range of sites of distant organs, primarily the lungs, is associated with gram-negative septicemia 4, 5, 6, 7, 8. The most common anaerobic pathogen is Fusobacterium Necrophorum 1, 6; other implicated pathogens are Streptococcus, Staphylococcus sensible or resistant to methicillin, Klebsiella Pneumoniae, Eschereichia Coli, Bacillus Cereus, Listeria or Pseudomonas Aeruginosa 4, 5, 8, 9.
Lemierre’s Syndrome may cause a wide range of ophthalmic complications6. In 2022, the most extensive analysis conducted on ophthalmic complications related to this pathology was published. Twenty-seven patients with ocular manifestations were analyzed from a large cohort of 712 cases of Lemierre’s Syndrome. The most prevalent symptoms and signs were periocular edema or eye swelling (38%) and decreased visual acuity (35%), followed by impaired eye movements/nerve palsy (28%) and proptosis (28%). The most frequent diagnoses explaining the ophthalmic complications were cerebral vein thrombosis (70%) and superior ophthalmic vein thrombosis (55%)4.
Kreuzpointner, R. et al. described only two cases related to Lemierre’s Syndrome 6, 13. The first reported case of endogenous endophthalmitis was by MA Ahad et al.13 The patient exhibited typical signs and symptoms of the syndrome, initially presenting oropharyngeal infection and empyema. Fusobacterium Necrophorum was isolated from blood cultures and the patient developed IJV thrombosis and metastatic bacterial endophthalmitis during the disease course. Ocular symptoms included decreased vision in the right eye and anterior uveitis, with a vitreous white mass observed during examination. Treatment involved topical steroids, Atropine and sensitive antibiotics, resulting in improved ocular condition within four days. The patient remained on systemic antibiotics for 8 weeks, leading to resolution of endophthalmitis. Notably, Kreuzpointner, R. et al. did not reference a second case6. Therefore, this article presents the third documented case of endogenous endophthalmitis related to Lemierre's Syndrome, contributing valuable insights to the scientific community.
Generally, endogenous endophthalmitis has a low prevalence (approximately 2–8% of all cases of endophthalmitis). Pathogenesis occurs when organisms reach the eye via the bloodstream and then cross the blood ocular barrier10. In case of Lemierre's Syndrome, it occurs from the entry of the causal organism through the oropharyngeal mucosa from trauma, inflammation, or tissue destruction and it spreads from an abscess through the deeper loose connective cervical tissues, via an hematogenous mechanism, or spreads via a lymphogenic mechanism in order to extend into the veins of the head or neck with the most frequent route being from the tonsil into the ipsilateral IJV. This will eventually activate platelets, the coagulation cascade and cause inflammation leading to thrombus formation and Lemierre’s syndrome’s progression. The spread of septic emboli from the IJV, or whichever vein the bacterium has seeded, can lead to the involvement of distant organs within the body14. In case of ophthalmic artery involvement due to sepsis, endogenous endophthalmitis may occur and worsen the ocular symptoms. Therefore, in the presence of worsening of the ocular symptoms, endogenous endophthalmitis should be promptly ruled out. While this complication is rare, its possibility implies that the rate of ophthalmic complications in patients with Lemierre’s syndrome might be even higher if these patients underwent standard ophthalmologic assessment even in the absence of ophthalmic symptoms or visible ophthalmic findings like chemosis, swelling and proptosis6.
It is considered that 25% of endophthalmitis cases due to Lemierre’s Syndrome are initially misdiagnosed10. Hence, the importance of accurate diagnosis. As stated in the title of the article written by JC Davis in 201215, the clinician may face the diagnostic dilemma in retinitis and endophthalmitis. In the present 17-year-old woman case, CMV retinitis was considered in the initial differential diagnosis based on the fundoscopic lesion, history of previous viral tonsillitis and limitations of further examination. Therefore, it was initially treated as such because it could not be ruled out with certainty. However, given the patient had negative CMV PCR results, CMV retinitis was deemed unlikely, and treatment targeted at this condition was discontinued15.
CMV retinitis occurs in the context of a systemic infection, characterized by full-thickness retinal necrosis that leaves a thin, atrophic and gliotic scar, potentially leading to retinal detachments as a common complication, often due to multiple retinal tears at the border of normal retina and the atrophic scar. Two clinical morphologic variants of CMV retinitis have been described: 1) fulminant or hemorrhagic, characterized by a more extensive area of retinal edema and necrosis, mixed with hemorrhage, often resembling a “pizza pie” or “cottage cheese and ketchup” appearance, occurring more frequently in the posterior pole; and 2) granular appearance, which affects more often in the periphery. For its diagnosis, CMV can be detected in the blood of the majority of patients with CMV retinitis either by culture or PCR of CMV from a blood specimen. In terms of the differential diagnosis, CMV retinitis is commonly confused with two other necrotizing retinitis, acute retinal necrosis and toxoplasmic retinitis, and syphilis should always be excluded 11, 12. Treatments for CMV retinitis have included intravenous antivirals (Ganciclovir, Foscarnet, Cidofovir, Valganciclovir) and intravitreal injections of either Ganciclovir or Foscarnet. Many patients, especially those with lesions threatening the fovea or optic nerve, are treated with an initial series of intravitreal injections of either Ganciclovir or Foscarnet, combined with systemic therapy (e.g. Valganciclovir).
The presence of ophthalmic involvement may represent a signal of cerebral vein involvement requiring prompt action6. Treatment of Lemierre’s Syndrome revolves around aggressive antibiotic treatment, anticoagulation therapy and surgical management. Delaying antibiotic treatment may increase mortality and affect long-term morbidity14. Prior to antibiotics, the disease carried a mortality rate of 32-90%, compared to 5-18% with antibiotic treatment5. Consequently, initial treatment should include broad-spectrum antimicrobial therapy, which is subsequently narrowed once the culprit bacterium is identified. Endogenous endophthalmitis should be treated with systemic antibiotics, combined or not with intravitreal antibiotics. Intravitreal Vancomycin is the most commonly selected agent for Gram positive coverage and Ceftazidime the most commonly used antibiotic for Gram negative infection. Vitrectomy can also be performed, usually with the administration of intravitreal antibiotics and vitreous sampling for microscopy and culture 10.
The case presented in this report adds to the short list of endogenous endophthalmitis related to Lemierre’s Syndrome. This patient meets the diagnostic criteria for Lemierre’s Syndrome, which includes primary infection in the oropharynx, positive blood cultures for Streptococcus Anginosus, imaging evidence of internal jugular venous thrombophlebitis and lung metastatic focus4. She was promptly managed with broad-spectrum antimicrobial therapy, along with intravitreal antibiotics, which were adjusted once the culprit bacterium was identified and depending on the evolution of the fundoscopic lesion. The patient’s prompt reporting of ocular symptoms such as decreased visual acuity and floaters, as well as the close ophthalmological follow-up, allowed for the prevention of complications in the affected and fellow eyes, and even systemic ones that could compromise the patient’s life. The lack of adequate consciousness in some of these patients hospitalized in the ICU may underestimate the presence of ophthalmic complications associated with this pathology, potentially delaying timely diagnosis and treatment. Therefore, and as emphasized by Kreuzpointner, R. et al, there is a need for an interdisciplinary approach to the management of patients with Lemierre’s Syndrome, with a routine involvement of ophthalmologists 3, 6.