Autologous Serum Tears for Treatment of Photoallodynia in Patients with Corneal Neuropathy: Efficacy and Evaluation with In Vivo Confocal Microscopy

Abstract

Objective: Patients suffering from corneal neuropathy may present with photoallodynia; i.e., increased light sensitivity, frequently with a normal slit-lamp examination. This study aimed to evaluate the efficacy of autologous serum tears (AST) for treatment of severe photoallodynia in corneal neuropathy and to correlate clinical findings with corneal subbasal nerve alterations by in vivo confocal microscopy (IVCM).

Methods: Retrospective case control study with 16 patients with neuropathy-induced severe photoallodynia compared to 16 normal controls. Symptom severity, clinical examination and bilateral corneal IVCM scans were recorded.

Results: All patients suffered from extreme photoallodynia (8.8±1.1) with no concurrent ocular surface disease. Subbasal nerves were significantly decreased at baseline in patients compared to controls; total nerve length (9208±1264 vs 24714±1056 μm/mm(2); P<.0001) and total nerve number (9.6±1.4 vs 28.6±2.0; P<.0001), respectively. Morphologically, significantly increased reflectivity (2.9±0.2 vs 1.8±0.1; P<.0001), beading (in 93.7%), and neuromas (in 62.5%) were seen. AST (3.6±2.1 months) resulted in significantly decreased symptom severity (1.6±1.7; P=.02). IVCM demonstrated significantly improved nerve parameters (P<.005), total nerve length (15451±1595 μm/mm(2)), number (13.9±2.1), and reflectivity (1.9±0.1). Beading and neuromas were seen in only 56.2% and 7.6% of patients.

Conclusion: Patients with corneal neuropathy-induced photoallodynia show profound alterations in corneal nerves. AST restores nerve topography through nerve regeneration, and this correlated with improvement in patient-reported photoallodynia. The data support the notion that corneal nerve damage results in alterations in afferent trigeminal pathways to produce photoallodynia.

Keywords: autologous serum tears; corneal neuropathy; laser in vivo confocal microscopy; light sensitivity; nerve growth factor; photoallodynia; regeneration.

Figure 1

IVCM images obtained at the level of the corneal subbasal nerve plexus demonstrate nerve alterations in patients of corneal neuropathy. A. Normal corneal subbasal nerve plexus. B. Nerve tracings using Neuron J to quantify the density of nerves. C. IVCM images showing significantly decreased corneal subbasal nerve plexus at baseline, prior to autologous serum tears therapy. Note the decrease in length and number of nerves, increased tortuosity, reflectivity, beading and formation of neuromas. D. IVCM image showing post-treatment findings of the patient shown at panel C. Note improvement in the plexus, still abnormal as compared to normal controls. Size bar=100μm.

Figure 2

Severity of symptoms pre- and post-treatment and improvement in symptom severity post-treatment.

Figure 3

IVCM images obtained at the level of the corneal subbasal nerve plexus demonstrate the improvement in the nerve density and morphology following treatment with autologous serum tears. A, C, E. Images at baseline showing increased reflectivity and tortuosity of nerves with presence of beading and neuromas. B, D, F. IVCM images post-treatment corresponding to same patients as A, C, E. Images after 3, 6 and 4 months, respectively, showing increased nerve density and decreased reflectivity, tortuosity, beading, and neuromas.

Figure 4

Comparison of subbasal nerve plexus density in patients suffering from corneal neuropathy, controls, and following treatment with ASTs. Bar graphs show corneal nerve alterations in pre-treatment and post-treatment eyes in patients and in the control group. A. Total number of nerves. B. Length of total nerves. C. Number of main nerve trunks. D. Length of main nerve trunks. E. Number of nerve branches. F. Length of nerve branches. ^*P<.001, compared to the control group by analysis of variance, ^†P<.001, compared to the pre-treatment group by paired t-test.

Figure 5

Comparison of the subbasal nerve plexus morphology in patients suffering from corneal neuropathy, controls, and following treatment with ASTs. Bar graphs showing corneal nerve alterations in pre-treatment and post-treatment eyes in patients and in the control group. A. Reflectivity of nerves. B. Tortuosity of nerves. C. Beading of nerves. D. Neuromas. ^*P<.001, compared to the control group by analysis of variance, ^†P<.001, compared to the pre-treatment group by paired t-test.