||Summary: Introduction • Definition: retinitis from the nerve o "-itis": inflammation or infection • Some key features: o Star-figure of exudate in the retina o Swollen optic nerve • Usually unilateral, but it can be bilateral. • In neuroretinitis, the optic nerve is swollen. Fluid leaks out from the optic disc. The fluid will appear in the macula. This fluid contains exudate, which forms the characteristic star-figure pattern because it involves the Henle's outer plexiform layer (Figure 1). Causes of Neuroretinitis • There are infectious and non-infectious (i.e. inflammatory and idiopathic) causes of neuroretinitis • Most cases are infectious neuroretinitis, mostly from Bartonella. Infectious Causes (Table 1) • Combination of swollen disc and star-figure of exudate should raise suspicion for infectious neuroretinitis • Infectious neuroretinitis can be caused by numerous infectious agents, each of which has its own test. • If positive, treat with antibiotics. • Infectious cause: Bartonella (usually Bartonella henselae) o Test: IgM and IgG (Figure 2) o Causes Cat Scratch Disease, the most common infectious neuroretinitis • Infectious cause: Syphilis o Test: IgG OR o Treponemal test followed by non-Treponemal test -Treponemal test examples: • Fluorescent Treponemal Antibody (FTA) • Hemagglutination for Treponemal Pallidum (MHTP) -Non-Treponemal test examples: • Rapid Plasma Reagent (RPR) • Venereal Disease Research Laboratory Test (VDRL) -Necessary to perform both Treponemal and non-Treponemal test • If Treponemal test is positive before treatment, it will stay positive after treatment • The non-Treponemal tests (RPR and VDRL) reflect activity of the disease • Examples of results of Treponemal test and non-Treponemal test o Positive Treponemal test and positive non-Treponemal test → positive for active Syphilis and need treatment o Positive Treponemal test and negative non-Treponemal test → prove you were treated with Penicillin in the past, repeat Treponemal test, or treat patient o Negative Treponemal test and positive non-Treponemal test → false-positive non-Treponemal test -Treponemal tests have higher sensitivity and specificity than non-Treponemal tests o Negative Treponemal test and negative non-Treponemal test → negative for Syphilis • Infectious cause: Lyme disease o Two-step testing process -ELISA is used first for screening -Confirmatory Western blot is performed if ELISA is positive • ELISA is not a very specific or sensitive test • CDC has requirements on what bands and #bands are acceptable for IgG and IgM o Ophthalmology normally orders IgG, because IgM is only for the rash, and we hardly see patients during the rash phase • Infectious cause: Tuberculosis o Does not have immunoglobulin because Tuberculosis does not produce an antibody-mediated hypersensitivity reaction o Test: Interferon Gamma Release Assay -Measures sensitized T-cells' response to TB-antigen -Tradenames include QuantiFERON and T-SPOT -Follow-up with chest x-ray • Other infectious causes: Hepatitis, Herpes family virus Non-infectious Causes • Inflammatory cause: Sarcoidosis • Idiopathic: Idiopathic Stellate Neuroretinitis -Bilateral neuroretinitis • Should be imaged, because papilledema can mimic the appearance of disc edema o Both have star-figure • Check blood pressure to rule-out malignant hypertension, which requires admission to hospital [Transcript of video] "Neuroretinitis is called that because there is infection or inflammation, the "-itis", and we're going to see a star figure of exudate in the retina and the optic nerve is swollen. So, it's retinitis from the nerve. It's usually unilateral, but it can be bilateral. So here, we have the swollen optic nerve. And in this particular example, here's the fovea. Because there's fluid leaking out from this disc, it will appear in the macula and the fluid in neuroretinitis contains exudate, and the exudate will make a star figure pattern because it is involving the Henle's outer plexiform layer. So, when we see the combination of a swollen disc and a star figure of exudate, that should raise the suspicion that this is an infectious neuroretinitis. The most common infectious neuroretinitis we see is Cat Scratch Disease, which is caused by Bartonella, usually Bartonella henselae, and so we test that patient with IgM and IgG. As you know the IgM goes up and then it goes down. The IgG lags behind; it goes up and then it goes down, but then becomes a memory B cell. Kind of stable level from memory B cell IgG. But you should also be thinking about other infectious causes of neuroretinitis. And that includes syphilis, for which the test is also an IgG. Or you can do a Treponemal test, either the Fluorescent Treponemal Antibody test or some T test. We know that a Treponemal test has a ‘T' in it, like FTA, Fluorescent Treponemal Antibody. Micro Hemagglutination for Treponemal Pallidum (MHTP). Or Treponemal Pallidum caused by agglutination. All of these have ‘T'-they're Treponemal tests, followed by a non-Treponemal test. The non-Treponemal tests don't have a ‘T' in them. Those are the RPR, Rapid Plasma Reagent, and the VDRL, the Venereal Disease Research Laboratory Test. So, you need both the Treponemal test and the non-Treponemal test, because once the Treponemal test is positive, even with treatment, the Treponemal test will stay positive. So, if you have a positive FTA, even if you are treated with an adequate dose of Penicillin, it just stays positive forever. However, the RPR and the VDRL reflect activity of disease. So, if the RPR is positive and the FTA is positive, then you have active disease and we have to treat it. If the RPR is positive but the Treponemal test is negative, that's probably a false-positive non-Treponemal test, because the Treponemal tests are more specific and sensitive. And if you have negative both, then you don't have Syphilis. If you have a positive Treponemal test but a negative non-Treponemal test-FTA positive, RPR or VDRL negative, then they have to have proof on a piece of paper that they were treated with Penicillin in the past. Or you have to repeat the Treponemal test or just treat them. In addition, you should be thinking about Lyme disease. And the testing for Lyme disease is a two-step process. We have to the ELISA, which is the screening. But even if it is positive, because the sensitivity and specificity of the test is not that great, we would do a confirmatory Western Blot. And the CDC has very specific requirements on what bands they will accept and what number of bands they will accept, both for IgM and IgG. And ophthalmology would normally order the IgG, because the IgM is only for the rash, and that looks like a bullseye or target called erythema chronicum migrans. But we hardly see the patient during the rash phase, so IgG is what we're looking for. Two-stage test: ELISA, if positive, Western Blot. And then we have to think about Tuberculosis. And Tuberculosis does not have any immunoglobulin because Tuberculosis is not that kind of reaction, it's not an antibody-mediated hypersensitivity reaction. In fact, it's kind of delayed type. And therefore, we have to use an assessment, a quantitative assay of interferon, called an Interferon Gamma Release Assay. This Interferon Gamma Release Assay measures sensitized T-cells' response to TB-antigen. So, if you've been seen with Tuberculosis before, we can take your blood and see if those sensitized T-cells will release interferon gamma in response to TB-antigen. And those have trade names like QuantiFERON and T-SPOT. We'd also do a chest x-ray here. You should also think about the inflammatory causes of neuroretinitis, like sarcoidosis. Other infectious agents can cause it, Hepatitis, Herpes family viruses. But really the main thing is Bartonella. And once you got a positive, you should treat it with antibiotics. If it's bilateral, I would image that, because papilledema can mimic the appearance of disc edema, with a star figure. If it's bilateral, you should check the blood pressure and make sure that it's not malignant hypertension, which would require admission to the hospital. But most cases are infectious neuroretinitis, and most cases are Bartonella. Some of the cases are Syphilis. Lyme and TB are rare. If no cause is found, idiopathic, which has an eponym, Idiopathic Stellate Neuroretinitis. That is a diagnosis of exclusion."