Corneal Nerve Regeneration after Self-Retained Cryopreserved Amniotic Membrane in Dry Eye Disease

Abstract

Purpose To evaluate the efficacy of self-retained cryopreserved amniotic membrane (CAM) in promoting corneal nerve regeneration and improving corneal sensitivity in dry eye disease (DED). Methods In this prospective randomized clinical trial, subjects with DED were randomized to receive CAM (study group) or conventional maximum treatment (control). Changes in signs and symptoms, corneal sensitivity, topography, and in vivo confocal microscopy (IVCM) were evaluated at baseline, 1 month, and 3 months. Results Twenty subjects (age 66.9 ± 8.9) were enrolled and 17 completed all follow-up visits. Signs and symptoms were significantly improved in the study group yet remained constant in the control. IVCM showed a significant increase in corneal nerve density in the study group (12,241 ± 5083 μm/mm2 at baseline, 16,364 ± 3734 μm/mm2 at 1 month, and 18,827 ± 5453 μm/mm2 at 3 months, p = 0.015) but was unchanged in the control. This improvement was accompanied with a significant increase in corneal sensitivity (3.25 ± 0.6 cm at baseline, 5.2 ± 0.5 cm at 1 month, and 5.6 ± 0.4 cm at 3 months, p < 0.001) and corneal topography only in the study group. Conclusions Self-retained CAM is a promising therapy for corneal nerve regeneration and accelerated recovery of the ocular surface health in patients with DED. The study is registered at clinicaltrials.gov with trial identifier: NCT02764814.

<p>Self-Retained Cryopreserved Amniotic Membrane for the Management of Corneal Ulcers</p>

“…Furthermore, use of cAM for NK is further supported by two recent studies, in which PKS was shown to promote corneal nerve regeneration in patients with severe dry eye disease and concurrently reduce corneal neuropathic pain. 37,38 These findings may shed light on the successful outcomes observed in this retrospective series, which predominantly comprised corneal ulcers with underlying NK. Further prospective studies are warranted to confirm our findings.…”

Treatment outcomes in the DRy Eye Amniotic Membrane (DREAM) study

“… 23 Such anti-inflammatory action exerted by CAM is retained in the water-soluble extract 24 , 25 and replicated by HC-HA/PTX3 purified from AM. 11 , 12 A third mechanism is CAM’s ability to regenerate corneal nerves as previously reported, 7 , 26 and this may explain the lasting effect. This notion is supported by the fact that NGF is abundantly present in CAM and is known to play an important role in nerve regeneration and epithelial healing.…”

“…Cryopreserved amniotic membrane (CAM) was used to treat DED with ocular surface involvement, and its short-term efficacy was attributed to its known potent anti-inflammatory effect. 6 More recently, John et al 7 further evaluated the potential effect of CAM in restoring corneal nerves in DED using in vivo confocal microscopy due to the known correlation between corneal nerve density and the severity of DED. 8 – 10 They showed CAM treatment significantly increased corneal nerve density which was correlated with improved corneal sensitivity and reduced dry eye symptoms.…”

“… 8 – 10 They showed CAM treatment significantly increased corneal nerve density which was correlated with improved corneal sensitivity and reduced dry eye symptoms. 7 This treatment effect was seen for 3 months and may be attributed to CAM’s rich composition of neurotrophic factors, particularly nerve growth factor (NGF). 11 – 13 However, these studies were conducted on a relatively small patient population, and further studies are needed to substantiate the findings.…”

<p>Amniotic Membrane Transplantation in Ophthalmology: An Updated Perspective</p>

“…160,161 One retrospective review by Macdonald et al 162 applied AMT for 5.4 (±2.8 days) on average with a sustained reduction in the DED marker (3.25±0.5 to 1.47±0.6) three months post operatively with improvement in both patient reported symptoms and clinical signs. Finally, other authors report how corneal nerve density can be significantly improved following AMT application, 163 potentially accelerating the recovery of the ocular surface health in patients with DED.…”