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Brief Report
July 2017

Use of Corneal Confocal Microscopy to Evaluate Small Nerve Fibers in Patients With Human Immunodeficiency Virus

Author Affiliations
  • 1Imperial College London, London, England
  • 2Faculty of Medicine, Weill Cornell Medicine-Qatar, Ar-Rayyan, Qatar
  • 3BG Universitätsklinikum Bergmannsheil GmbH, Ruhr University, Bochum, Germany
  • 4Department of Ophthalmology, University Eye Hospital, Dusseldorf, Germany
  • 5National Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, London, England
  • 6University College London Institute of Ophthalmology, London, England
  • 7Queen’s University Belfast, Belfast, Northern Ireland
  • 8Institute of Cardiovascular Sciences, Cardiac Centre, School of Medicine, University of Manchester, Manchester, England
JAMA Ophthalmol. 2017;135(7):795-800. doi:10.1001/jamaophthalmol.2017.1703
Key Points

Question  Can in vivo corneal confocal microscopy be used to assess changes in corneal nerve fiber structure and Langerhans cell density in patients with human immunodeficiency virus (HIV)–associated sensory neuropathy?

Findings  In this cohort study of 20 patients with HIV, a decrease in corneal nerve fiber density and an increase in corneal nerve tortuosity were observed in patients with HIV-associated sensory neuropathy when compared with patients without neuropathy, with no change in Langerhans cell density.

Meaning  In vivo corneal confocal microscopy is a noninvasive ophthalmic imaging technique that could aid in the diagnosis and longitudinal monitoring of patients with HIV-associated sensory neuropathy.


Importance  Objective quantification of small fiber neuropathy in patients with human immunodeficiency virus (HIV)–associated sensory neuropathy (HIV-SN) is difficult but needed for diagnosis and monitoring. In vivo corneal confocal microscopy (IVCCM) can quantify small fiber damage.

Objective  To establish whether IVCCM can identify an abnormality in corneal nerve fibers and Langerhans cells in patients with and without HIV-SN.

Design, Setting, and Participants  This prospective, cross-sectional cohort study was conducted between July 24, 2015, and September 17, 2015. Twenty patients who were HIV positive were recruited from adult outpatient clinics at Chelsea and Westminster Hospital NHS Foundation Trust in England. These patients underwent IVCCM at Moorfields Eye Hospital NHS Foundation Trust in London, England, and the IVCCM images were analyzed at Weill Cornell Medicine–Qatar in Ar-Rayyan, Qatar. Patients were given a structured clinical examination and completed validated symptom questionnaires and the Clinical HIV-Associated Neuropathy Tool. Results from patients with HIV were compared with the results of the age- and sex-matched healthy control participants (n = 20). All participants were classified into 3 groups: controls, patients with HIV but without SN, and patients with HIV-SN.

Main Outcomes and Measures  Comparison of corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length, corneal nerve fiber tortuosity, and corneal Langerhans cell density between healthy controls and patients with HIV with and without SN.

Results  All 40 participants were male, and most (≥70%) self-identified as white. Of the 20 patients with HIV, 14 (70%) had HIV-SN. This group was older (mean [SD] age, 57.7 [7.75] years) than the group without HIV-SN (mean [SD] age, 42.3 [7.26] years) and the controls (mean [SD] age, 53.8 [10.5] years). Corneal nerve fiber density was reduced in patients with HIV compared with the controls (26.7/mm2 vs 38.6/mm2; median difference, −10.37; 95.09% CI, −14.27 to −6.25; P < .001) and in patients with HIV-SN compared with those without (25.8/mm2 vs 30.7/mm2; median difference, −4.53; 95.92% CI, −8.85 to −0.26; P = .03). Corneal nerve branch density and corneal nerve fiber length were reduced in patients with HIV, but no differences were identified between those with neuropathy and without neuropathy (corneal nerve branch density: 95.83/mm2 for the controls vs 72.37/mm2 for patients with HIV; median difference, −24.53; 95.32% CI, −50.62 to −3.13; P = .01; and corneal nerve fiber length: 28.4 mm/mm2 for the controls vs 21.9 mm/mm2 for patients with HIV; median difference, −5.24; 95.09% CI, −8.83 to −1.38; P = .001). Tortuosity coefficient was increased in patients with HIV compared with controls (16.44 vs 13.95; median difference, 2.34; 95.09% CI, 0.31 to 4.65; P = .03) and in those with HIV-SN compared with those without (17.84 vs 14.18; median difference, 4.32; 95.92% CI, 0.68-9.23; P = .01). No differences were identified in corneal Langerhans cell density (19.84 cells/mm2 for the controls vs 41.43 cells/mm2 for patients with HIV; median difference, 9.38; 95% CI, −12.51 to 26.34; P = .53).

Conclusions and Relevance  In vivo corneal confocal microscopy could be used in the assessment of HIV-SN, but larger studies are required to confirm this finding.