Corneal Sensation and Subbasal Nerve Alterations in Patients with Herpes Simplex Keratitis

Abstract

Purpose-To study and correlate corneal sensation in patients with herpes simplex keratitis (HSK) with density and morphology of subbasal corneal nerves by in vivo confocal microscopy (IVCM).Design-Prospective, cross-sectional, controlled, single-center study.Participants-Thirty-one eyes with the diagnosis of acute (n=7) or chronic (n=24) HSK and the contralateral clinically unaffected eyes were studied and compared to normal controls (n=15). (Confoscan 4, Nidek) and corneal esthesiometry (Cochet-Bonnet) of the central cornea were performed bilaterally in all patients and controls. Patients were grouped into normal (>5.5 cm), mild (>2.5 to 5.5cm) and severe (≤2.5 cm) loss of sensation. Methods-IVCMMain Outcome Measures-Changes in corneal nerve density, total nerve number, main nerve trunks, branching and tortuosity were evaluated after IVCM and correlated to corneal sensation, disease duration, and number of recurrences.Results-HSK eyes, as compared to controls, demonstrated significant (p<0.001) decrease in mean nerve density (448.9±409.3 vs. 2,258.4±989.0 μm/frame), total nerve number (5.2±4.5 vs. 13.1±3.8), main nerve trunks (2.3±1.6 vs. 4.7±1.2) and nerve branches (3.2 ± 4.3 vs. 9.8±3.3). In contralateral unaffected eyes, mean nerve density (992.7±465.0 μm/frame), total nerve number (7.8±3.3), and branches (4.5±2.3) were significantly decreased as compared to controls (p<0.002). Reduced nerve density, total nerve count and main trunks in HSK eyes were significantly correlated with corneal sensation across all subgroups (p<0.001). Nerve density decreased within days of infection and was correlated to frequency of episodes in patients with HSK (p<0.02).Conclusions-In vivo confocal microscopy reveals that the loss of corneal sensation in HSK correlates strongly with profound diminishment of the subbasal nerve plexus after herpes simplex virus (HSV) infection. Surprisingly, the contralateral clinically unaffected eyes also demonstrated a

Comparison of Standard Versus Wide-Field Composite Images of the Corneal Subbasal Layer by In Vivo Confocal Microscopy

“…[10][11][12][13] Furthermore, in addition to providing trophic and sensory functions, corneal nerves have been shown to play an important role in the maintenance of ocular surface epithelial health and function. [14][15][16][17] As epithelial DCs and subbasal nerves may change in a variety of ocular surface and corneal conditions, such as dry eye disease, neurotrophic keratopathy, infectious keratitis, diabetes, and contact lens wear, 3,5,[18][19][20][21][22] quantification of these two structures, which can be achieved by IVCM, is of significant importance. The high resolution of IVCM images is inherently associated with a drawback, which is a relatively small field of view of the images.…”

“…In vivo confocal microscopy imaging was performed by a method previously described in detail. 21 In brief, the distance from the cornea to the microscope was kept stable by a singleuse disposable sterile polymethylmethacrylate cap (Tomo-Cap; Heidelberg Engineering), filled with a layer of the lubricant 2 mg/g carbomer-containing gel (Vidisic gel; Bausch & Lomb, Heidelberg, Germany). Both eyes were instilled with topical anesthesia using Oxybuprocaine hydrochloride 4 mg (Conjuncain EDO; Dr Gerhard Mann Chem.-Pharm.…”

Corneal sensitivity and morphology of the corneal subbasal nerve plexus in primary congenital glaucoma

“…No significant differences in corneal sensitivity are explained by the fact that abnormal corneal sensitivity is noted with a subbasal nerve density below the threshold of 835 mm per frame. 28 Furthermore, patients with PCG had significantly reduced central corneal thickness and significantly higher density of corneal basal epithelial cells compared with controls. It has been well established that corneal nerves have important trophic effects on epithelial cell growth and proliferation, keratocyte homeostasis, and corneal wound healing.…”

“…[19][20][21] Rosenberg et al 27 have reported that reduction of subbasal plexus nerve fibers correlates with loss of corneal sensitivity in patients with diabetic neuropathy, while tortuosity of subbasal nerves correlated significantly with the severity of diabetic neuropathy. Hamrah et al 28 have recently described significant morphological changes in corneal subbasal nerve plexus in patients with herpes simplex keratitis and showed that reduction of nerve density correlated significantly with loss of corneal sensitivity in such patients.…”

Corneal nerve alterations in acute Acanthamoeba and fungal keratitis: an in vivo confocal microscopy study

“…Although herpetic keratitis (HK) is the entity most consistently implicated in neurotrophic keratopathy and loss of the sub-basal nerve plexus, 3 other infectious disease states may be associated with corneal nerve alterations as well. In Acanthamoeba keratitis (AK) and fungal keratitis (FK), defining corneal nerve involvement on a histopathological level may aid in clarifying the disease processes and in potentially developing novel treatment modalities.…”