title: Subclinical capillary changes in non-proliferative diabetic retinopathy.
abstract: OBJECTIVE
  To establish adaptive optics scanning laser ophthalmoscopy as a method to detect and characterize microscopic signs of diabetic retinopathy in capillaries and cone photoreceptors in the parafovea.
  
  
  METHODS
  Recently, adaptive optics scanning laser ophthalmoscope (AOSLO) has enabled noninvasive assessment of photoreceptors, capillaries, and leukocytes in the retinas of live human subjects. Repeated application of AOSLO imaging along with comparison to fluorescein angiography was used to track individual capillaries near the foveal avascular zone (FAZ) from one eye affected with severe non-proliferative diabetic retinopathy. Fluorescein angiography was used to identify clinical signs of diabetic retinopathy, such as microaneurysms and intraretinal microvascular abnormalities, and corresponding regions were imaged and assessed using the AOSLO. In addition, the structural integrity of photoreceptors and the spatial distribution of leukocytes around the parafoveal capillary network were quantitatively assessed.
  
  
  RESULTS
  Capillaries and cone photoreceptors were visualized using the AOSLO without the use of injected contrast agents. Although the majority of capillaries were stable over a period of 16 months, one capillary at the edge of the FAZ dropped out, leading to a small but significant increase in FAZ size. Longitudinal assessment of the capillaries also showed microaneurysm formation and disappearance as well as the formation of tiny capillary bends similar in appearance to intraretinal microvascular abnormalities. The leukocytes in the capillary network were found to preferentially travel through the same routes in all four visits, suggesting that these channels are robust against small changes to the surrounding capillaries. In this eye, cone photoreceptor spacing was increased in the fovea when compared with normal data but stable across all visits.
  
  
  CONCLUSIONS
  AOSLO imaging can be used to longitudinally track capillaries, leukocytes, and photoreceptors in diabetic retinopathy. Capillary changes that can be detected include dropout of individual capillaries as well as formation and disappearance of microaneurysms.
authors.affiliation: Joint Graduate Group in Bioengineering, University of California, Berkeley, Berkeley, California 94720-2020, USA.
authors.forename: Johnny
authors.initials: J
authors.lastname: Tam
authors.forename: Kavita P
authors.initials: KP
authors.lastname: Dhamdhere
authors.forename: Pavan
authors.initials: P
authors.lastname: Tiruveedhula
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Lujan
authors.forename: Robert N
authors.initials: RN
authors.lastname: Johnson
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Bearse
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Adams
authors.forename: Austin
authors.initials: A
authors.lastname: Roorda
mesh_terms: D000328:Adult; D002196:Capillaries / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000473:pathology; D003930:Diabetic Retinopathy / Q000209:etiology / Q000473:pathology*; D018450:Disease Progression; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005584:Fovea Centralis / Q000098:blood supply*; D005654:Fundus Oculi; D006801:Humans; D008297:Male; D009887:Ophthalmoscopy / Q000379:methods; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012171:Retinal Vessels / Q000473:pathology*