title: Degeneration and Regeneration of Subbasal Corneal Nerves after Infectious Keratitis: A Longitudinal In Vivo Confocal Microscopy Study.
abstract: OBJECTIVE
  To investigate the longitudinal alterations of subbasal corneal nerves in patients with infectious keratitis (IK) during the acute phase, cessation of treatment, and the recovery phase by in vivo confocal microscopy (IVCM).
  
  
  METHODS
  Prospective, longitudinal, case-control, single-center study.
  
  
  METHODS
  Fifty-six eyes of 56 patients with the diagnosis of bacterial (n=28), fungal (n=15), or Acanthamoeba (n=13) keratitis were included in the study. Thirty eyes of 30 normal volunteers constituted the control group.
  
  
  METHODS
  Corneal sensation and serial IVCM of the central cornea were performed prospectively using the Heidelberg Retina Tomograph 3/Rostock Cornea Module (Heidelberg Engineering, Heidelberg, Germany). The IVCM images were assessed at 3 time points: at the acute phase (first visit to the cornea service), at cessation of antimicrobial treatment, and up to 6 months after the resolution of infection.
  
  
  METHODS
  Total nerve number and length, main nerve trunks, branching, and corneal sensation were assessed during the follow-up period.
  
  
  RESULTS
  Corneal nerves were reduced significantly during the acute phase in eyes with IK compared with controls across all subgroups, with total nerve length of 5.47±0.69 mm/mm2 versus 20.59±1.06 mm/mm2 (P<0.0001). At the cessation of treatment, corneal nerves in patients with IK had regenerated, including total nerve length (8.49±0.94 mm/mm2; P=0.02) and nerve branch length (4.80±0.37 mm/mm2; P=0.005). During the recovery phase, after resolution of infection, corneal nerves regenerated further, including total nerve length (12.13±1.97 mm/mm2; P=0.005), main nerve trunk length (5.80±1.00 mm/mm2; P=0.01), and nerve branch length (6.33±0.76 mm/mm2; P=0.003) as compared with the acute phase, but were still significantly lower when compared with controls (P<0.05 for all parameters). Corneal degeneration and regeneration correlated with corneal sensation (r=0.47; P=0.0009).
  
  
  CONCLUSIONS
  Patients with IK who sustain profound loss of corneal nerves during the acute phase of infection demonstrate increased corneal nerve density during the first 6 months after the resolution of infection. However, despite significant nerve regeneration, corneal nerve density does not recover fully and remains low compared to controls. By providing an objective methodology to monitor corneal re-innervation, IVCM adds potentially important findings that may have implications for clinical management and surgical planning.
authors.affiliation: Ocular Surface Imaging Center, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Cornea & Refractive Surgery Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Rodrigo T
authors.initials: RT
authors.lastname: Müller
authors.affiliation: Ocular Surface Imaging Center, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Cornea & Refractive Surgery Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Farshad
authors.initials: F
authors.lastname: Abedi
authors.affiliation: Ocular Surface Imaging Center, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Cornea & Refractive Surgery Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cruzat
authors.affiliation: Ocular Surface Imaging Center, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Cornea & Refractive Surgery Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Deborah
authors.initials: D
authors.lastname: Witkin
authors.affiliation: Ocular Surface Imaging Center, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Cornea & Refractive Surgery Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Neda
authors.initials: N
authors.lastname: Baniasadi
authors.affiliation: Ocular Surface Imaging Center, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Cornea & Refractive Surgery Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Bernardo M
authors.initials: BM
authors.lastname: Cavalcanti
authors.affiliation: Ocular Surface Imaging Center, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Arsia
authors.initials: A
authors.lastname: Jamali
authors.affiliation: Cornea & Refractive Surgery Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: James
authors.initials: J
authors.lastname: Chodosh
authors.affiliation: Cornea & Refractive Surgery Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
authors.affiliation: Cornea & Refractive Surgery Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Deborah
authors.initials: D
authors.lastname: Pavan-Langston
authors.affiliation: Ocular Surface Imaging Center, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Cornea & Refractive Surgery Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Boston Image Reading Center and Cornea Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts. Electronic address: phamrah@tuftsmedicalcenter.org.
authors.forename: Pedram
authors.initials: P
authors.lastname: Hamrah
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D003315:Cornea / Q000294:innervation*; D003320:Corneal Ulcer / Q000188:drug therapy / Q000382:microbiology / Q000469:parasitology / Q000473:pathology*; D015817:Eye Infections / Q000188:drug therapy / Q000382:microbiology / Q000469:parasitology / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009410:Nerve Degeneration / Q000473:pathology*; D009416:Nerve Regeneration / Q000502:physiology*; D011446:Prospective Studies; D016037:Single-Blind Method; D014276:Trigeminal Nerve / Q000473:pathology / Q000502:physiology; D020433:Trigeminal Nerve Diseases / Q000473:pathology*
chemical_list: D000900:Anti-Bacterial Agents; D000981:Antiprotozoal Agents