Severe photophobia, color vision disorders, or visual hallucinations and periocular pain are symptoms frequently reported by patients affected by corneal or neuro-ophthalmic involvement.

Blurred vision, floaters, and worsening of visual acuity are typical symptoms of vitreoretinal inflammatory involvement [60, 61].

During the flu-like illness of LD, a nonspecific follicular conjunctivitis may occur in 1/10 of patients, and it is frequently associated with lid or conjunctival chemosis and/or episcleritis. A patient – even if a child – with any of these manifestations should be questioned as to endemic area, tick bite, skin rash, and arthritis and should undergo serological testing [62, 63]. Children and people living or working in rural endemic areas are the most exposed.

Early-stage manifestations The first sign of ocular involvement is follicular conjunctivitis related to flu-like illness symptoms, followed some weeks later by nummular keratitis [63]. Superficial and interstitial keratitis can be localized in the limbus area and can produce corneal limbus ulcers (Fig. 5.3). Exposure keratitis related to the seventh peripheral nerve palsy is also described [64–66].

Borrelia-associated crystalline keratopathy is a rare reported manifestation [67].

Late-stage manifestations Episcleritis [68] (Fig. 5.4), iritis, anterior uveitis, vitritis (with “spider’s web” aspect), intermediate uveitis, and posterior involvement occur infrequently and usually appear in the late stages [69–71].

Uveitis is usually a late finding, and anterior uveitis is frequently associated with papillitis. It is characterized by granulomatous keratic precipitates or various degrees of flare and cells (Fig. 5.5); sometimes, posterior synechiae (usually in the inferior part of the iris) and iris nodules may be present [72, 73].

Intermediate uveitis typically affects children and presents as hyalitis and granulomatous vitritis ranging from traces to 4+ and spider’s web aspect [60, 74] (Fig. 5.6).

Vitreous snowballs typically are yellow-white inflammatory aggregates and are found in the mid vitreous and inferior periphery. Snowbanks are exudates on the pars plana which, when present, are usually found inferiorly, but may also extend all around the retinal periphery; this finding is usually associated with severe forms of the disease and needs aggressive therapy [75] (Fig. 5.7). Retinal changes are represented by arteriolar winding and vascular sheathing mainly of peripheral veins, neovascularization, and retinal detachment [74, 75].

Posterior uveitis may show (1) a serous posterior pole detachment (if bilateral, it is difficult to distinguish from Vogt-Koyanagi-Harada syndrome) (Figs. 5.8, 5.9, 5.10, 5.11, and 5.12), (2) a peripheral multifocal choroiditis with an aspect similar to that of sarcoidosis (Figs. 5.13 and 5.14), and/or (3) cotton wool spots, typically followed by recurrent episodes of anterior uveitis [76, 77]. A distinct clinical entity related to LD posterior pole involvement is peripheral multifocal choroiditis with multiple small retinal lesions associated with intraocular inflammation [78, 79].

Retinal vasculitis is actually more frequent than in previous reports (Fig. 5.15) and involves both the arterial and the venous system and may result in vascular occlusion [61, 80, 81]. Occlusive vasculitis, mainly of retinal veins, has a similar appearance to syphilitic retinal vasculitis.

Panuveitis is rare but a blinding disease [82].

Fluorescein angiography in cases of neuroretinitis may show retinal edema and areas of cystoid patchy and peripapillary hyperfluorescence in the macula and peripapillary area; it shows also focal leakage as a sign of retinal vasculitis which can affect either veins or arteries [72, 78, 82] (Fig. 5.16 and Figs. 5.17, 5.18, 5.19, 5.20, 5.21, and 5.22).

Recombinant vaccines have been developed, but they are not yet available on the market [103–108].

There is no consensus regarding which therapeutic protocol should be used in the ocular involvement of LD. Specific and early antibiotic therapy is proven to treat all LD clinical manifestations [109, 110]. Difficulties can arise in the antibiotic choice for children or pregnant or breastfeeding women [111–119].

Specific treatment is shown in Table 5.1.

Children, pregnant, or breastfeeding women and people allergic to penicillin-derived drugs have to be given a 2–3 weeks course with erythromycin (500 mg/QID) [115–123].

Reinfections are usually treated in the same way as first infection [124].

It is proved that chronic persistent LB does not benefit from antibiotic therapies, even if prolonged for over 1 year and although intravenously administered [125–128].

When the nervous system is affected by Lyme disease, an aggressive intravenous antibiotic treatment is usually necessary although some patients develop persistent neurologic symptoms (multiple recurrences or long-lasting disease) [83].

Treatment failure is rare and sometimes bound to Borrelia persistence within the involved tissues with consequent tissue damage or postinfective autoimmune syndrome and sometimes associated with a late correct therapeutic approach related to a first wrong diagnosis in subjects with arthritis. Frequently, in facts, patients affected by systemic LD are misdiagnosed with many autoimmune diseases, i.e. multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis, fibromyalgia and erroneously treated, converting a treatable infectious disease into a chronic illness [127].