Autologous serum application in the treatment of neurotrophic keratopathy

Ophthalmology. 2004 Jun;111(6):1115-20. doi: 10.1016/j.ophtha.2003.10.019.


Objective: To evaluate the effect of autologous serum application for epithelial disorders in neurotrophic keratopathy (NK).

Design: Retrospective, noncomparative case series.

Participants: Fourteen eyes of 11 patients with NK seen at Tokyo Dental College, Ichikawa General Hospital, Department of Ophthalmology, were studied.

Intervention: Twenty percent topical autologous serum eye drops were applied 5 to 10 times daily until resolution of the NK. Patients underwent routine ophthalmic examinations, including slit-lamp examination, corneal fluorescein dye testing, Cochet-Bonnet corneal sensitivity (Luneau, France), and best-corrected visual acuity (BCVA) measurements before and at the end of the treatment. Moreover, serum samples from 10 healthy volunteers were studied for the levels of substance P (SP), insulinlike growth factor (IGF-1), and nerve growth factor (NGF) by using radioimmunoassay and enzyme-linked immunosorbent assay techniques. Tear samples from 3 healthy subjects also were analyzed for NGF and IGF-1 levels by the same techniques.

Main outcome measures: The changes in corneal disease state, corneal sensitivity, and BCVA with treatment were evaluated. The levels of neural healing factors like SP, IGF-1, and NGF in serum as well as NGF and IGF-1 in tears of healthy subjects also were examined.

Results: The epithelial disorders healed completely in all eyes within 6 to 32 days (mean, 17.1+/-8.0 days), with a decrease in corneal scarring. The mean pretreatment corneal sensitivity was 11.8+/-11.6 mm, which increased to 30.0+/-22.9 mm after treatment at the last follow-up. Five eyes attained normal corneal sensitivity with treatment. The BCVA improved by >2 Landolt lines in 78.6% of the eyes. The mean concentrations of SP in diluted and undiluted serum were 31.4+/-8.4 pg/ml and 157.0+/-42.1 pg/ml, respectively. The mean respective concentrations of IGF-1 in diluted and undiluted serum were 31.4+/-14.8 ng/ml and 157.0+/-73.9 ng/ml. The mean concentrations for NGF were 93.6+/-63.5 pg/ml and 468.3+/-317.4 pg/ml in serum samples with and without dilution, respectively. The mean concentration of NGF in tears was found to be 54 pg/ml. Insulinlike growth factor 1 was not detected in tears in this study.

Conclusions: Autologous serum harbors neurotrophic factors. Autologous serum treatment may provide neural healers to the compromised ocular surface and seems promising for the restoration of the ocular surface epithelial integrity in patients with NK.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cornea / innervation*
  • Corneal Diseases / blood
  • Corneal Diseases / physiopathology
  • Corneal Diseases / therapy*
  • Cranial Nerve Diseases / blood
  • Cranial Nerve Diseases / physiopathology
  • Cranial Nerve Diseases / therapy*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Insulin-Like Growth Factor I / analysis
  • Male
  • Middle Aged
  • Nerve Growth Factor / blood
  • Ophthalmic Nerve* / physiopathology
  • Radioimmunoassay
  • Retrospective Studies
  • Serum*
  • Substance P / blood
  • Tears / metabolism


  • Substance P
  • Insulin-Like Growth Factor I
  • Nerve Growth Factor