Correlation Between Corneal Nerve Density and Symptoms of Small Fiber Neuropathy in Patients With Fibromyalgia: The Confounding Role of Severe Anxiety or Depression

Abstract

Objective: A consistent line of investigation proposes fibromyalgia as a dysautonomia-associated neuropathic pain syndrome. Comorbid anxiety or depression amplifies fibromyalgia symptoms. The recent recognition of small fiber neuropathy in fibromyalgia patients supports the neuropathic nature of the illness. Corneal confocal microscopy accurately identifies small nerve fiber pathology. The newly developed Small-Fiber Symptom Survey captures the spectrum of small fiber neuropathy symptoms. We aimed to correlate corneal nerve density with different fibromyalgia disease severity questionnaires including the Small-Fiber Symptom Survey. We defined the possible confounding role of comorbid anxiety or depression severity in the clinical-pathological association.Methods: This is a case series of 28 women with fibromyalgia. A single ophthalmologist quantified corneal subbasal plexus nerve density. Corneal innervation was correlated (Spearman ρ) with the following clinical questionnaires scores: Small-Fiber Symptom Survey, Revised Fibromyalgia Impact Questionnaire, and COMPASS-31 (Composite Autonomic Symptom Survey 31-Item Score). Validated inquiry forms assessed the comorbid anxiety and/or depression severity.Results: There were no clinical-pathological correlations in the group as a whole. In the subgroup of fibromyalgia women without severe anxiety or depression (n = 13), there was a strong negative correlation between corneal nerve density with the Small-Fiber Symptom Survey score (ρ = −0.771, p = 0.002) and COMPASS-31 score (ρ = −0.648, p = 0.017). Patients with profound anxiety or depression (n = 15) had more intense symptoms but had not clinical-pathological correlations.Conclusions: Small fiber neuropathy and dysautonomia symptoms correlate with corneal denervation in women with fibromyalgia without severe anxiety or depression. This clinical-pathological association reinforces fibromyalgia as a dysautonomia-related neuropathic pain syndrome. Severe anxiety or depression distorts fibromyalgia symptoms.Practical point: Corneal confocal microscopy may become a useful procedure to study fibromyalgia patients.

Fibromyalgia: one year in review 2022

“…In the second, Ramìrez et al (40) found correlations between corneal denervation and SFN and the symptoms of dysautonomia in female FM patients unaffected by severe anxiety or depression, whereas their profoundly anxious or depressed counterparts showed no clinical-pathological correlations even though their symptoms were more intense, thus confirming that severe psychiatric symptoms play a confounding role.…”

“…• Neurophysiologically, the pattern of brain activation is not due to functional or structural alterations in the areas involved in acute pain, thus chronic pain is not just "longer-lasting pain" (36,37). • The Pain Detect Questionnaire (PDQ), the Douleur Neuropathique 4 questions (DN4), sural nerve crosssectional area and corneal denervation can be used to non-invasively diagnose SFN (39,40).…”

Dorsal root ganglia: fibromyalgia pain factory?

“…The eye cornea is the most pain-sensitive part of the body owing to the extremely dense small fiber innervation. This feature makes the cornea the ideal site to study small nerve fiber pathology [8].…”

“…Small fiber neuropathy is a denervating disease. Fibromyalgia patients without marked anxiety or depression display strong correlation between corneal denervation and small fiber neuropathy symptom burden [8]. A tentative explanation for the peripheral denervation seen in small fiber neuropathy is DRG nuclear degeneration.…”

Association between biophysical properties and anxiety in patients with sensitive skin

“…Another proposed underlying pathogenic factor for SS development is the presence of small fiber neuropathy 5 . The association between increased anxiety levels and small fiber neuropathy is well established in fibromyalgia, diabetic neuropathy, and burning mouth syndrome 6–10 . The role of depression and psychiatric factors in the development of sensitive skin has also been shown in the previous studies 11–13 .…”