NEURORETINITIS

Signs and Symptoms

While neuroretinitis can present in any age group due to several potential causative etiologies, patients are typically younger, and the condition commonly occurs in children. In fact, the majority of patients are under the age of 20.1-13 There is no sexual predilection.

Neuroretinitis typically presents as a unilateral, acute, painless loss of vision. Rarely, it presents bilaterally and, just as rarely, without symptoms. Alternatively, vision may decrease as low as finger-counting level.1-13 The typical visual field loss is a central or cecocentral scotoma.2,14 A relative afferent pupillary defect (RAPD) will be present if the condition is unilateral or markedly asymmetric. Interestingly, the magnitude of the RAPD will be small relative to what one would expect given the profound degree of vision loss. In fact, in many unilateral cases, there is no detectable RAPD, despite profound vision loss in the affected eye.2,14

Ophthalmoscopically, there will be a noticeably edematous disc. There may also be peripapillary hemorrhages due to venous stagnation. Occasionally there will be a mild vitritis overlying the disc. Initially, there will be a serous retinal detachment extending from the disc to the macula. The key diagnostic feature in well-developed neuroretinitis is the presence of macular exudates in the form of a florid macular star.1-13 However, this finding may not occur for several weeks after onset of visual symptoms, with the diagnosis not apparent early in the course of the disease. It is not uncommon to have a serous retinal detachment within the posterior pole in association with the advent of disc edema. This is highly suspicious for early neuroretinitis with the macular exudates ensuing later.2,13

Numerous systemic conditions have been seen in association with neuroretinitis, including toxoplasmosis, toxocariasis, measles, syphilis, Lyme disease, herpes simplex and zoster, mumps, tuberculosis and leptospirosis.15-25 However, the most common cause by far is Bartonella henselae—the organism responsible for cat scratch disease.26-36 Occasionally, cat scratch disease will be caused by Bartonella quintana.37 In cat scratch disease neuroretinitis, there may be an antecedent history of fever, malaise, and/or lymphadenopathy, occurring several weeks preceding the visual loss. There may also be an antecedent history of a cat scratch or flea bite.26-37

Pathophysiology

Neuroretinitis was initially identified by Leber in 1916 as a retinopathy associated with unilateral vision loss and disc edema. Upon discovering that the focus of dysfunction was the optic nerve rather than the retina, the condition was later renamed Leber’s idiopathic stellate neuroretinitis.38 Neuroretinitis, like most optic neuropathies, has many proposed mechanisms, though the exact pathophysiologic pathway has not been identified. Because the majority of cases are due to infectious etiologies, it is plausible that cell invasion with proinflammatory activation occurs.39

Visual loss is predominately from the retinal edema rather than optic nerve dysfunction. This is evidenced by the fact that the visual field defects reflect a retinal cause as well as the relative mild degree (or absence) of afferent pupillary defect in the face of profound vision loss.2,14 While the macular exudates are characteristic of this condition, they may not be evident upon early presentation and it may be several weeks (typically two) before they develop.2,40 After development of the disc and retinal edema, there will be spontaneous resolution and fluid resorption. The aqueous phase of the edema resolves the fastest, leaving the accumulated lipid exudates within the outer plexiform layer, forming the characteristic macular star.

Management

When encountering neuroretinitis, it is important to consider and evaluate patients medically for all possible causes. A history should be elicited for exposure to cats, flea and tick bites, travel to lyme endemic areas, exposure to sexually transmitted disease, lymphadenopathy, skin rashes, malaise, myalgia and fever. Tests that should be ordered (as dictated by the history) include lyme titer, toxoplasmosis titer, toxocariasis titer, purified protein derivative skin testing, fluorescent treponemal antibody absorption test (FTA-ABS), rapid plasma reagin (RPR) and chest X-ray to look for evidence of tuberculosis. However, as the most common cause is infection by B. henselae or B. quintana from a cat scratch, one must carefully examine for these entities.41-44 Cat scratch disease can be identified by immunoassay antibody testing for B. henselae and B. quintana.5,14,45

Initially, neuroretinitis may be subtle in regards to macular findings. When the macular edema and star are not present, the patient may seemingly manifest only disc edema, making the actual diagnosis elusive. However, optical coherence tomography (OCT) may be a valuable adjunctive diagnostic test. It has been noted that subretinal fluid not visible on clinical examination or fluorescein angiography may be readily identified with OCT, making it an adjunctive imaging tool in the diagnosis and follow up of patients with cat scratch-related neuroretinitis.46,47

The prognosis for visual recovery in neuroretinitis is generally excellent, especially if the cause is cat scratch disease. Most patients will have a return to normal or near normal vision without treatment.2,14,30 While neuroretinitis from cat scratch disease is typically a self-limiting condition with an excellent prognosis, antimicrobial therapy may be used to hasten recovery. Successful oral agents include Rifadin (rifampin, Aventis), ciprofloxacin, doxycycline, sulfamethoxazole and trimethoprim.2,3,14,28,29,48-50 A commonly used therapy is doxycycline 100mg PO BID for one month.2,3,14,28,29 Additionally, oral steroids may be used to mitigate inflammation.49 Recently, research has shown that intravitreal injection of Avastin (bevacizumab, Genentech) improves visual acuity while also decreasing macular edema.51,52 However, since neuroretinitis enjoys such a good prognosis for recovery, such invasive therapy may not be justified, especially when one considers that this information comes from case reports rather than controlled clinical trials.

In neuroretinitis, the disc edema will resolve in approximately eight weeks, and the macular exudates will resolve over several months. There may be a residual macular pigmentary atrophy or optic atrophy, which will occasionally lead to a poor visual outcome.2,3,26

Clinical Pearls

Neuroretinitis should be suspected in cases of disc edema with profuse adjacent retinal edema and painless vision loss with a relatively mild afferent pupillary defect. A confirmatory sign is the appearance of a macular star within 10 to 14 days.

Very few entities will mimic neuroretinitis, with its characteristic macular star. Mimicking entities include malignant hypertension and anterior ischemic optic neuropathy.

The afferent pupillary defect will be remarkably mild (or even absent) despite severe vision loss.

The absence of pain with eye movements greatly helps to differentiate neuroretinitis from demyelinating optic neuritis. Patients with neuroretinitis need not have the same concerns for the development of multiple sclerosis.

Fleas may be the vectors of the Bartonella organisms and hence neuroretinitis. History of an actual cat scratch or bite is not always necessary in order to make this diagnosis.

While antibiotics are frequently used for cat scratch disease neuroretinitis, there are no controlled clinical trials that indicate a better clinical outcome from this therapy. The same can be said for the use of oral steroids and intravitreal anti-angiogenic medications.

1. Reddy AK, Morriss MC, Ostrow GI, et al. Utility of MR imaging in cat-scratch neuroretinitis. Pediatr Radiol. 2007;37(8):840-3.

2. Wade NK, Levi L, Jones MR, et al. Optic disk edema associated with peripapillary serous retinal detachment: an early sign of systemic Bartonella henselae infection. Am J Ophthalmol. 2000;130(3):327-34.

3. Ghauri RR, Lee AG. Optic disk edema with a macular star. Surv Ophthalmol. 1998;43(3):270-4.

4. Labalette P, Bermond D, Dedes V, et al. Cat-scratch disease neuroretinitis diagnosed by a polymerase chain reaction approach. Am J Ophthalmol. 2001;132(4):575-6.

5. Sander A, Berner R, Ruess M. Serodiagnosis of cat scratch disease: response to Bartonella henselae in children and a review of diagnostic methods. Eur J Clin Microbiol Infect Dis. 2001;20(6):392-401.

6. Lombardo J. Cat-scratch neuroretinitis. J Am Optom Assoc. 1999;70(8):525-30.

7. Donnio A, Buestel C, Ventura E, et al. Cat-scratch disease neuroretinitis. J Fr Ophtalmol. 2004;27(3):285-90.

8. Ulrich GG, Waecker NJ, Meister SJ, et al. Cat scratch disease associated with neuroretinitis in a 6-year-old girl. Ophthalmology. 1992;99(2):246-9.

9. Depeyre C, Mancel E, Besson-Leaud L, et al. Abrupt visual loss in children. Three case studies of ocular bartonellosis. J Fr Ophtalmol. 2005;28(9):968-75.

10. Shoari M, Katz BJ. Recurrent neuroretinitis in an adolescent with ulcerative colitis. J Neuroophthalmol. 2005;25(4):286-8.

11. Weiss AH, Beck RW. Neuroretinitis in childhood. J Pediatr Ophthalmol Strabismus. 1989;26(4):198-203.

12. Besson-Leaud L, Mancel E, Missotte I, et al. Sudden sight impairment revealing a cat-scratch disease: report of three cases. Arch Pediatr. 2004;11(10):1209-11.

13. Saatci AO, Oner FH, Kargi A, Unilateral neuroretinitis and periparillary serous retinal detachment in cat-scratch disease. Korean J Ophthalmol. 2002;16(1):43-6.

14. Suhler EB, Lauer AK, Rosenbaum JT. Prevalence of serologic evidence of cat scratch disease in patients with neuroretinitis. Ophthalmology. 2000;107(5):871-6.

15. Moreno RJ, Weisman J, Waller S. Neuroretinitis: an unusual presentation of ocular toxoplasmosis. Ann Ophthalmol. 1992;24(2):68-70.

16. Arruga J, Valentines J, Mauri F, et al. Neuroretinitis in acquired syphilis. Doc Ophthalmol. 1986;64:23-9.

17. Karma A, Stenborg T, Summanen P, et al. Long-term followup of chronic Lyme neuroretinitis. Retina. 1996;16(6):505-9.

18. Margo CE, Sedwick LA, Rubin ML. Neuroretinitis in presumed visceral larva migrans. Retina. 1986;6(2);95-8.

19. Neppert B. Measels retinitis in an immunocompetent child. Klinische Monatsblatter fur Augenheilkunde. 1994;205:156-60.

20. Foster RE, Lowder CY, Meisler DM, et al. Mumps neuroretinitis in an adolescent. Am J Ophthalmol. 1990;110(1):91-3.

21. Stechschulte SU, Kim RY, Cunningham ET Jr. Tuberculous neuroretinitis. J Neuro-Ophthalmol. 1999;19(3):201-4.

22. Jensen J. A case of herpes zoster ophthalmicus complicated with neuroretinitis. Acta Ophthalmol. 1948;26:551-5.

23. Johnson BL, Wisotzkey HM. Neuroretinitis associated with herpes simplex encephalitis in an adult. Am J Ophthalmol. 1977;83;481-9.

24. Scott IU, Flynn HW, Al-Attar L, et al. Bilateral optic disc edema in patients with severe systemic arterial hypertension: clinical features and visual acuity outcomes. Ophthalmic Surg Lasers Imaging. 2005;36(5):374-80.

25. Lee AG, Beaver HA. Acute bilateral optic disk edema with a macular star figure in a 12-year-old girl. Surv Ophthalmol. 2002;47(1):42-9.

26. Brazis PW, Stokes HR, Ervin FR. Optic neuritis in cat scratch disease. J Clin Neuroophthalmol. 1986;6(3):172-4.

27. Chrousos GA, Drack AV, Young M, et al. Neuroretinitis in cat scratch disease. J Clin Neuroophthalmol. 1990;10(2):92-4.

28. Matsuo T, Kato M. Submacular exudates with serous retinal detachment caused by cat scratch disease. Ocul Immunol Inflamm. 2002;10(2):147-50.

29. Kodama T, Masuda H, Ohira A. Neuroretinitis associated with cat-scratch disease in Japanese patients. Acta Ophthalmol Scand. 2003;81(6):653-7.

30. Rosen B. Management of B. henselae neuroretinitis in cat-scratch disease. Ophthalmology. 1999;106(1):1-2.

31. Besada E, Woods A, Caputo M. An uncommon presentation of Bartonella-associated neuroretinitis. Optom Vis Sci. 2002;79(8):479-88.

32. Rosen BS, Barry CJ, Nicoll AM, et al. Conservative management of documented neuroretinitis in cat scratch disease associated with Bartonella henselae infection. Aust N Z J Ophthalmol. 1999;27(2):153-6.

33. De Schryver I, Stevens AM, Vereecke G, et al. Cat scratch disease (CSD) in patients with stellate neuroretinitis: 3 cases. Bull Soc Belge Ophtalmol. 2002;(286):41-6.

34. Ziemssen F, Bartz-Schmidt KU, Gelisken F. Secondary unilateral glaucoma and neuroretinitis: atypical manifestation of cat-scratch disease. Jpn J Ophthalmol. 2006;50(2):177-9.

35. Veselinović D. Bartonella henselae as a cause of optical nerve neuritis. Vojnosanit Pregl. 2006;63(11):971-4.

36. Chai Y, Yamamoto S, Hirayama A, et al. Pattern visual evoked potentials in eyes with disc swelling due to cat scratch disease-associated neuroretinitis. Doc Ophthalmol. 2005;110(2-3):271-5.

37. George JG, Bradley JC, Kimbrough RC, et al. Bartonella quintana associated neuroretinitis. Scand J Infect Dis. 2006;38(2):127-8.

38. Dreyer RF, Hopen G, Gass JDM, Smith JL. Leber’s idiopathic stellate neuroretinitis. Arch Ophthalmol 1984;102:1140-5.

39. Dehio C. Molecular and cellular basis of bartonella pathogenesis. Annu Rev Microbiol. 2004;58:365-90.

40. Brazis PW, Lee AG. Optic disk edema with a macular star. Mayo Clin Proc. 1996;71(12):1162-6.

41. Anders UM, Taylor EJ, Doty DC, et al. Neuroretinitis secondary to Bartonella henselae in the emergent setting. Am J Emerg Med. 2014; pii: S0735-6757(14)00869-9.

42. Pérez G J, Munita S JM, Araos B R, et al. Cat scratch disease associated neuroretinitis: clinical report and review of the literature. Rev Chilena Infectol. 2010;27(5):417-22.

43. Raihan AR, Zunaina E, Wan-Hazabbah WH, et al. Neuroretinitis in ocular bartonellosis: a case series Clin Ophthalmol. 2014;8:1459-66.

44. Zekraoui Y, Megzari A, El Alloussi T, Berraho A. Unilateral neuroretinitis revealing cat-scratch disease. Rev Med Interne. 2011;32(4):e46-8.

45. Flexman JP, Chen SC, Dickeson DJ, et al. Detection of antibodies to Bartonella henselae in clinically diagnosed cat scratch disease. Med J Aust. 1997;166(10):532-5.

46. Habot-Wilner Z, Zur D, Goldstein M, et al. Macular findings on optical coherence tomography in cat-scratch disease neuroretinitis. Eye (Lond). 2011;25(8):1064-8.

47. Cruzado-Sánchez D, Tobón C, Lujan V, et al. Neuroretinitis caused by Bartonella henselae: a case with follow up through optical coherence tomography. Rev Peru Med Exp Salud Publica. 2013;30(1):133-6.

48. Metz CH, Buer J, Bornfeld N, Lipski A. Bilateral Bartonella henselae neuroretinitis with stellate maculopathy in a 6-year-old boy. Infection. 2012;40(2):191-4.

49. Biancardi AL, Curi AL. Cat-scratch disease. Ocul Immunol Inflamm. 2014;22(2):148-54.

50. Karolak J, Gotz-Wipckowska A. Neuroretinitis in cat scratch disease. Klin Oczna. 2010;112(4-6):131-4.

51. Moon SJ, Misch DM. Intravitreal Bevacizumab for Macular Edema from Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis. Ophthalmic Surg Lasers Imaging. 2010 Mar;1-3.

52. Cakir M, Cekiç O, Bozkurt E, et al. Combined intravitreal bevacizumab and triamcinolone acetonide injection for idiopathic neuroretinitis. Ocul Immunol Inflamm. 2009;17(3):221-3.