This retrospective case series aimed to evaluate ocular manifestations of LD by reviewing cases identified in the PubMed database that were published during 1988–2025. We included published articles in PubMed up until March 15, 2025, that described clinical manifestations of various forms of ocular LD. We conducted the literature search in PubMed by using the search terms “ocular Lyme” and “ocular and variations, with B. burgdorferi.” Inclusion criteria included articles that discussed >1 case report of ocular manifestations of LD. Exclusion criteria included inability to obtain full text, text in language other than English, and studies that did not discuss clinical manifestations of a specific case. We noted a paucity of articles that met CDC criteria at the time the cases were reported. Despite those limitations, we were able to illustrate the specific variety of ocular conditions by screening 176 articles; among the reviewed full texts, 29 were eligible for sufficient analysis. We excluded 2 texts because no English versions of the texts were available. We reviewed 27 publications (Table; Appendix Table). In order of decreasing assurance that the patient had LD were microbiologic evidence (e.g., DNA) or culture-positive test results for B. burgdorferi, meeting CDC criteria for LD with serologic conversion, CDC criteria otherwise being met, and CDC criteria not being met.

The reviewed literature (Table; Appendix Table) highlights diverse ocular manifestations of LD and the basis for their diagnosis and method for treatment. Of the 38 cases we analyzed, 5 cases had microbiologic proof of LD (10–14) (Table). Cases that had microbiologic proof were 2 cases of anterior uveitis, 1 case of intermediate uveitis, 1 case of abducens nerve palsy with anterior uveitis, and 1 case of intranuclear ophthalmoplegia.

Reports of ocular involvement in LD are relatively rare; such cases are sometimes linked to early infiltration into the eye by B. burgdorferi bacteria or B. burgdorferi remaining dormant in the eye and then manifesting with symptoms later (4). The reported cases we describe do not include a reaction of the eye from a tick bite occurring on or around the eye. Ocular LD demonstrates a broad spectrum of manifestations, most commonly various forms of uveitis (anterior, intermediate, posterior, and panuveitis) but also cranial nerve palsies, optic neuritis, retinal vasculitis, scleritis, and other rare ocular findings, often accompanied by systemic symptoms such as fatigue, arthralgia, and influenza-like illness, which underscore LD’s multisystemic nature. Of the 38 cases we reviewed, only 5 had definitive microbiologic confirmation through PCR or culture, whereas the remainder were classified as probable or possible on the basis of clinical features and serologic testing, which varied in consistency, reflecting historical diagnostic challenges.

First reported in the 1980s, shortly after B. burgdorferi was identified as the causative agent, ocular LD was initially described in case reports of conjunctivitis, uveitis, optic neuritis, and cranial nerve palsies. Certain cases of uveitis may be confused with conjunctivitis (pink eye) (Figure). Although diagnostic methods advanced in the 1990s and 2000s with improved serologic assays and PCR testing, microbiologic proof for ocular LD cases has remained rare. Our findings are consistent with previous literature, which has also documented the diversity of manifestations, the predominance of uveitis, the rarity of microbiologic confirmation, and variability in adherence to diagnostic guidelines, particularly in older reports. Similar studies include systematic reviews by Lu and Zand in 2022 (1), which analyzed LD-associated optic neuritis; Klaeger and Herbort in 2010 (3), which focused on retinal vascular changes; Johnson et al. in 2018 (7), which studied broader LD manifestations, including ocular findings; and multiple case series from the 1980s through 2000s, such as Fatterpekar et al. in 2002 (4) describing orbital LD (1,3,4,7).

The heterogeneity of ocular manifestations found in patients with microbiologic proof of LD highlights the importance of testing for B. burgdorferi in patients with otherwise unexplained ocular manifestations. In addition, very few publications provided direct microbiologic proof of LD. Ideally, to recognize the possible ocular manifestations of LD, the presence of microbiologic proof of B. burgdorferi in some part of the body would be necessary.

Limitations of this study include the lack of microbiologic proof in most cases, heterogeneity in diagnostic criteria, small sample size, retrospective design with reliance on published case reports susceptible to reporting bias, incomplete or inconsistent clinical data, and temporal variability, given that many cases were published decades ago before modern diagnostic tools and treatment protocols. Those factors limit generalizability of case report findings to current clinical practice.

This comprehensive but limited analysis of published cases highlights clinical symptoms of possible or probable cases of LD. The successful outcomes in most cases, despite some requiring prolonged or repeated treatment, underscore the necessity of a multidisciplinary approach. Going forward, more comprehensive descriptions of ocular involvement should be published. This retrospective case series highlights the importance of further studies that can provide direct microbiologic proof for diagnosis of LD and guide the treatment of ocular manifestations in LD. Those measures will help us determine if ocular LD is an emerging condition.

In summary, LD can have, albeit rarely, a wide variety of ocular manifestations, most commonly uveitis, cranial nerve palsies, and optic neuritis. When evaluating a patient who lives or travels in an area of high LD prevalence, keeping LD in the differential diagnosis is important. A patient may seek primary care and clinicians in variety of subspecialties such as rheumatology, ophthalmology, infectious diseases, and neurology because of the various clinical manifestations of the illness. Therefore, all physicians need to be aware of the possibility of LD and be knowledgeable of how to test for it (or be ready to refer the patient to a colleague with expertise in LD) and report such cases to public health officials (6).