Ophthalmic signs in Ugandan adults with HIV-associated cryptococcal meningitis: A nested analysis of the ASTRO-CM cohort

Rachel R Atherton, Jayne Ellis, Fiona V Cresswell, Joshua Rhein, David R Boulware, Rachel R Atherton, Jayne Ellis, Fiona V Cresswell, Joshua Rhein, David R Boulware

Abstract

Cryptococcal meningitis is a leading cause of morbidity and mortality among HIV-infected persons, accounting for 15% of AIDS-related deaths. Visual disturbance is commonly reported, and a wide range of ophthalmic signs may be present on examination. There is limited published literature to date describing the range and incidence of ophthalmic signs in HIV-associated cryptococcal meningitis. Nested within the Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis (ASTRO-CM) trial (ClinicalTrials.gov number: NCT01802385), we conducted an observational study of 696 Ugandan adults with HIV-associated cryptococcal meningitis. Patients were screened for visual disturbance and external ophthalmic signs at initial presentation and at follow-up appointments over 18 weeks. Assessment comprised simple clinical history and basic examination and required no specialist equipment. More than a quarter of our cohort demonstrated ocular signs or symptoms, which were observed throughout the study period. A broad range of ocular signs were demonstrated: these included neurological signs (10.9%), localized ocular pathology (4.5%), and evidence of concurrent systemic disease (12.9%). The range of signs observed demonstrates the complexities of case management in patients with advanced HIV and cryptococcosis and also the importance of basic ocular examination in low resource settings. There remains an urgent need for studies conducting comprehensive ocular examination in patients with HIV-associated cryptococcal meningitis; these studies should include formal assessment of visual acuity, slit lamp examination and dilated indirect ophthalmoscopy. Prospective studies should investigate whether there is a correlation between reported visual disturbance and objective signs, in order to further clarify the underlying mechanisms and to guide effective diagnosis, follow-up and management.

Keywords: Cryptococcus; HIV; cryptococcal meningitis; ocular; ophthalmic; visual.

Conflict of interest statement

No competing interests were disclosed.

References

    1. Rajasingham R, Smith RM, Park BJ, et al. : Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis. 2017;17(8):873–881. 10.1016/S1473-3099(17)30243-8
    1. Moodley A, Rae W, Bhigjee A, et al. : Early Clinical and Subclinical Visual Evoked Potential and Humphrey’s Visual Field Defects in Cryptococcal Meningitis. PLoS One. 2012;7(12):e52895. 10.1371/journal.pone.0052895
    1. Moodley A, Bhigjee A: Visual loss in HIV-associated cryptococcal meningitis: A case series and review of the mechanisms involved.2007;1–9.
    1. Merkler AE, Gaines N, Baradaran H, et al. : Direct Invasion of the Optic Nerves, Chiasm, and Tracts by Cryptococcus neoformans in an Immunocompetent Host. Neurohospitalist. 2015;5(4):217–222. 10.1177/1941874415569072
    1. Mao F, Sun H, Li D: [Ophthalmic manifestations in acquired immune deficiency syndrome patients with cryptococcal meningitis]. Zhonghua Yan Ke Za Zhi. 2015;51(5):364–368, Accessed October 6, 2017. 10.3760/cma.j.issn.0412-4081.2015.05.012
    1. Kestelyn P, Taelman H, Bogaerts J, et al. : Ophthalmic manifestations of infections with Cryptococcus neoformans in patients with the acquired immunodeficiency syndrome. Am J Ophthalmol. 1993;116(6):721–727, Accessed October 6, 2017. 10.1016/S0002-9394(14)73472-5
    1. Okun E, Butler WT: Ophthalmologic Complications of Cryptococcal Meningitis. Arch Ophthalmol. 1964;71:52–57, Accessed October 6, 2017. 10.1001/archopht.1964.00970010068009
    1. Battu RR, Biswas J, Jayakumar N, et al. : Papilloedema with peripapillary retinal haemorrhages in an acquired immunodeficiency syndrome (AIDS) patient with cryptococcal meningitis. Indian J Ophthalmol. 2000;48(1):47–9.
    1. Andreola C, Ribeiro MP, de Carli CR, et al. : Multifocal Choroiditis in Disseminated Cryptococcus neoformans Infection. Am J Ophthalmol. 2006;142(2):346–348. 10.1016/j.ajo.2006.03.024
    1. Espino Barros Palau A, Morgan ML, Foroozan R, et al. : Neuro-ophthalmic presentations and treatment of Cryptococcal meningitis-related increased intracranial pressure. Can J Ophthalmol. 2014;49(5):473–7. 10.1016/j.jcjo.2014.06.012
    1. Aderman CM, Gorovoy IR, Chao DL, et al. : Cryptococcal choroiditis in advanced AIDS with clinicopathologic correlation. Am J Ophthalmol Case Rep. 2018;10:51–54. 10.1016/J.AJOC.2018.01.045
    1. Chen J, Chai C, Teoh SC: Cryptococcal-related exudative retinal detachment. Eye (Lond). 2011;25(9):1234–1235. 10.1038/eye.2011.100
    1. Wykoff CC, Albini TA, Couvillion SS, et al. : Intraocular Cryptococcoma. Arch Ophthalmol. 2009;127(5):700–2. 10.1001/archophthalmol.2008.620
    1. Krishnamoorthy A, Joel A, Abhilash KP: Cryptococcal Meningitis with Multiple Cranial Nerves Palsies: A Review of Literature. J Glob Infect Dis. 2015;7(3):123–124. 10.4103/0974-777X.161739
    1. Liyanage DS, Pathberiya LP, Gooneratne IK, et al. : Cryptococcal meningitis presenting with bilateral complete ophthalmoplegia: a case report. BMC Res Notes. 2014;7(1):328. 10.1186/1756-0500-7-328
    1. Sloan D, Parris V: Cryptococcal meningitis: epidemiology and therapeutic options. Clin Epidemiol. 2014;6:169–82. 10.2147/CLEP.S38850
    1. Kuriakose CK, Mishra AK, Vanjare HA, et al. : Visual Disturbance in Patients with Cryptococcal Meningitis: The Road Ahead. J Neurosci Rural Pract. 2017;8(1):151–152. 10.4103/0976-3147.193560
    1. Tugume L, Morawski BM, Abassi M, et al. : Prognostic implications of baseline anaemia and changes in haemoglobin concentrations with amphotericin B therapy for cryptococcal meningitis. HIV Med. 2017;18(1):13–20. 10.1111/hiv.12387
    1. Rex JH, Larsen RA, Dismukes WE, et al. : Catastrophic visual loss due to Cryptococcus neoformans meningitis. Medicine (Baltimore). 1993;72(4):207–224, Accessed June 6, 2018. 10.1097/00005792-199307000-00001

Source: PubMed

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