Efficacy of self-retained cryopreserved amniotic membrane for treatment of neuropathic corneal pain

Abstract

Purpose: Treatment of neuropathic corneal pain (NCP) remains intricate, and involves a long-term combined multistep approach. The self-retained cryopreserved amniotic membrane (PROKERA^®, Bio-Tissue, Miami,FL) has been utilized for multiple ocular surface disorders. We evaluate the efficacy, safety, and tolerability of ProKera^® Slim [PKS] and ProKera^® Clear [PKC] in the treatment of NCP.

Methods: Retrospective case series of 9 patients who received PKS/PKC for the acute treatment of NCP. Patient demographics, prior therapies, clinical examination, duration of PKS/PKC retention, changes in pain severity, corneal subbasal nerve density and morphology by in vivo confocal microscopy (IVCM; HRT3/RCM, Heidelberg Engineering, Heidelberg, Germany), and adverse events were recorded.

Results: PKS/PKC were placed in 10 eyes of 9 patients. Pain severity improved by 72.5 ± 8.4% (from 6.3 ± 0.8 to 1.9 ± 0.6, scale 1-10, p = 0.0003) after retention for 6.4 ± 1.1 days. Despite shorter retention for 4.0 ± 0.7 days in patients with ring dysesthesia (4 eyes) or premature implant disengagement (2 eyes), pain severity still improved by 63.1 ± 12.5% (from 6.8 ± 1.0 to 2.4 ± 0.9, p = 0.009). During a follow-up of 9.3 ± 0.8 months, two patients reported recurrence of pain after 2.3 and 9.6 months respectively, treated effectively with additional PKS/PKC. IVCM showed a 36.6 ± 17.6% increase in total nerve density, from 17,700.9 ± 1315.7 to 21,891.3 ± 2040.5 μm/mm² (p = 0.047), while the fellow PKS/PKC-untreated eyes did not show a significant interval change. Main nerve trunk and branch nerve densities were not statistically different. Dendritiform cell density decreased from 46.0 ± 8.2 to 32.0 ± 6.0 cells/mm² (p = 0.01).

Conclusions: PKS/PKC provide a safe and effective treatment approach to achieve sustained pain control in patients with NCP.

Keywords: Amniotic membrane; Cornea; Neuralgia; Neuropathic pain; Pain; prokera.

Figure 1

Average severity of pain before and after first PKS/PKC placement in all patients (A), in whom pain severity improved by 72.5 ± 8.4 % after treatment. Average severity of pain before and after PKS/PKC placement improved by 63.1 ± 12.5 % in patients where the amniotic membrane was removed before complete dissolution of the membrane (B), and 76.7 ± 8.7 % in patients who retained the membrane for the planned period of time (C). **p<.01, ***p<.001, compared to the pre-treatment group by paired t-test.

Figure 2

Representative IVCM pictures of patients #2 and 9, who were imaged before (A–D) and then again 36 (E, F) and 63 (G, H) days after PKS/PKC placement, respectively. For each patient, treated eyes are presented on the left column and untreated eyes, on the right.

Figure 3

Comparison of total nerve density in the central corneal subbasal plexus pre- and post-self-retained cryopreserved amniotic membrane in treated and untreated eyes imaged with IVCM, as well as reference controls, showing a 36.6 ± 17.6% increment after PKS/PKC treatment (A). Main nerve trunk (B) and branch nerve (C) densities, as well as presence of microneuromas (D) and dendritiform cell density (E) were also compared before and after PKS/PKC placement in treated and untreated eyes, and to reference controls. *p<.05, **p<.01, compared to fellow eyes by unpaired t-test, and to the pre-treatment group by paired t-test. n= 4 patients.