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Yureeda Qazi, Shruti Aggarwal, Bernardo Cavalcanti, Andrea Cruzat, Leslie Wu, Perry Rosenthal, Pedram Hamrah; In Vivo Confocal Microscopy Demonstrates a Profound Increase in Immune Dendritic Cells and Decrease in Corneal Nerves in Patients with Post-Refractive Surgery Keratoneuralgia. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3711.
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To analyze subbasal corneal nerve and immune cell changes in post-refractive surgery corneal pain patients, and their correlation to clinical signs and symptoms.
Laser in vivo confocal microscopy (IVCM) images of 17 patients with keratoneuralgia after refractive surgery (LASIK: n=28 eyes; PRK: n=5 eyes), and 62 controls (n=62 eyes), were analyzed retrospectively by two masked observers for subbasal nerves, and immune dendritic (DC) and inflammatory cells (IC). Keratoneuralgia was confirmed by the presence of pain with PROSE devices and lack of a response to proparacaine. Detailed history, symptom assessment (Ocular Surface Disease Index [OSDI] questionnaire) and a clinical examination (slit-lamp biomicroscopy) were obtained.
Patients had constant pain and photophobia with sensitivity to air (94%) and chemical fumes (47%). Although minimal corneal fluorescein staining was noted, a significant loss in lengths of total subbasal nerves compared to controls (12.8±4.7 vs. 24.3±3.9 mm/mm2, p<0.001) and branches (4.4±2.1 vs. 13.2±3.1mm/mm2, p<0.001), as well as increased tortuosity (2.9±0.6 vs. 1.8±0.5, p<0.001) were noted. Further, a 5-fold increase in DC (102.1±92 vs. 24.6±24.9 cells/mm2, p<0.001) and IC densities (10.9±9.3 vs. 0.1±0.2 cells/ mm2, p<0.001) was seen. The decrease in total nerve length was associated with increased OSDI severity (R= -0.7, p<0.001) and tortuosity correlated with sensitivity to fumes (r= 0.5, p<0.001). Moreover, IC density correlated with OSDI severity (R= 0.7, p<0.001) and photophobia (R= 0.8, p<0.001). DC density was correlated with sensitivity to air (R= 0.6, p<0.001).
In post-refractive surgery keratoneuralgia, despite minimal findings on clinical exam, subclinical changes in subbasal nerves and increased immune and inflammatory cells are seen on IVCM. These IVCM findings correlate with symptoms. IVCM may thus provide new insights into the pathogenesis of corneal pain, which is debilitating and otherwise poorly understood.
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