Skip to main content
The British Journal of Ophthalmology logoLink to The British Journal of Ophthalmology
. 2000 Nov;84(11):1285–1290. doi: 10.1136/bjo.84.11.1285

Evaluation of the Zeiss retinal vessel analyser

K Polak 1, G Dorner 1, B Kiss 1, E Polska 1, O Findl 1, G Rainer 1, H Eichler 1, L Schmetterer 1
PMCID: PMC1723319  PMID: 11049956

Abstract

AIM—To investigate the reproducibility and sensitivity of the Zeiss retinal vessel analyser, a new method for the online determination of retinal vessel diameters in healthy subjects.
METHODS—Two model drugs were administered, a peripheral vasoconstrictor (the α receptor agonist phenylephrine) and a peripheral vasodilator (the nitric oxide donor sodium nitroprusside) in stepwise increasing doses. Nine healthy young subjects were studied in a placebo controlled double masked three way crossover design. Subjects received intravenous infusions of either placebo or stepwise increasing doses of phenylephrine (0.5, 1, or 2 µg/kg/min) or sodium nitroprusside (0.5, 1, or 2 µg/kg/min). Retinal vessel diameters were measured with the new Zeiss retinal vessel analyser. Retinal leucocyte velocity, flow, and density were measured with the blue field entoptic technique. The reproducibility of measurements was assessed with coefficients of variation and intraclass correlation coefficients.
RESULTS—Placebo and phenylephrine did not influence retinal haemodynamics, although the α receptor antagonist significantly increased blood pressure. Sodium nitroprusside induced a significant increase in retinal venous and arterial diameters (p<0.001 each), leucocyte density (p=0.001), and leucocyte flow (p=0.024) despite lowering blood pressure to a significant degree. For venous and arterial vessel size measurements short term coefficients of variation were 1.3% and 2.6% and intraclass correlation coefficients were 0.98 and 0.96, respectively. The sensitivity was between 3% and 5% for retinal veins and 5% and 7% for retinal arteries.
CONCLUSIONS—These data indicate that the Zeiss retinal vessel analyser is an accurate system for the assessment of retinal diameters in healthy subjects. In addition, nitric oxide appears to have a strong influence on retinal vascular tone.



Full Text

The Full Text of this article is available as a PDF (159.8 KB).

Figure 1  .

Figure 1  

Effect of stepwise increasing doses of placebo (broken lines), phenylephrine, or sodium nitroprusside (solid lines) on retinal venous and arterial diameters. Data are presented as means (SEM) (n = 9). At the highest dose of phenylephrine and sodium nitroprusside only seven subjects were eligible for analysis. Asterisks indicate significant changes versus placebo.

Figure 2  .

Figure 2  

Effect of stepwise increasing doses of placebo (broken lines), phenylephrine, or sodium nitroprusside (solid lines) on leucocyte velocity, density of leucocytes, and leucocyte flow. Data are presented as means (SEM) (n = 9). At the highest dose of phenylephrine and sodium nitroprusside only seven subjects were eligible for analysis. Asterisks indicate significant changes versus placebo.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chakravarthy U., Stitt A. W., McNally J., Bailie J. R., Hoey E. M., Duprex P. Nitric oxide synthase activity and expression in retinal capillary endothelial cells and pericytes. Curr Eye Res. 1995 Apr;14(4):285–294. doi: 10.3109/02713689509033528. [DOI] [PubMed] [Google Scholar]
  2. Chen H. C., Patel V., Wiek J., Rassam S. M., Kohner E. M. Vessel diameter changes during the cardiac cycle. Eye (Lond) 1994;8(Pt 1):97–103. doi: 10.1038/eye.1994.19. [DOI] [PubMed] [Google Scholar]
  3. Delori F. C., Fitch K. A., Feke G. T., Deupree D. M., Weiter J. J. Evaluation of micrometric and microdensitometric methods for measuring the width of retinal vessel images on fundus photographs. Graefes Arch Clin Exp Ophthalmol. 1988;226(4):393–399. doi: 10.1007/BF02172974. [DOI] [PubMed] [Google Scholar]
  4. Deussen A., Sonntag M., Vogel R. L-arginine-derived nitric oxide: a major determinant of uveal blood flow. Exp Eye Res. 1993 Aug;57(2):129–134. doi: 10.1006/exer.1993.1107. [DOI] [PubMed] [Google Scholar]
  5. Donati G., Pournaras C. J., Munoz J. L., Poitry S., Poitry-Yamate C. L., Tsacopoulos M. Nitric oxide controls arteriolar tone in the retina of the miniature pig. Invest Ophthalmol Vis Sci. 1995 Oct;36(11):2228–2237. [PubMed] [Google Scholar]
  6. Dumskyj M. J., Aldington S. J., Dore C. J., Kohner E. M. The accurate assessment of changes in retinal vessel diameter using multiple frame electrocardiograph synchronised fundus photography. Curr Eye Res. 1996 Jun;15(6):625–632. doi: 10.3109/02713689609008902. [DOI] [PubMed] [Google Scholar]
  7. Dumskyj M. J., Eriksen J. E., Doré C. J., Kohner E. M. Autoregulation in the human retinal circulation: assessment using isometric exercise, laser Doppler velocimetry, and computer-assisted image analysis. Microvasc Res. 1996 May;51(3):378–392. doi: 10.1006/mvre.1996.0034. [DOI] [PubMed] [Google Scholar]
  8. Formaz F., Riva C. E., Geiser M. Diffuse luminance flicker increases retinal vessel diameter in humans. Curr Eye Res. 1997 Dec;16(12):1252–1257. doi: 10.1076/ceyr.16.12.1252.5021. [DOI] [PubMed] [Google Scholar]
  9. Forster B. A., Ferrari-Dileo G., Anderson D. R. Adrenergic alpha 1 and alpha 2 binding sites are present in bovine retinal blood vessels. Invest Ophthalmol Vis Sci. 1987 Nov;28(11):1741–1746. [PubMed] [Google Scholar]
  10. Gidday J. M., Zhu Y. Nitric oxide does not mediate autoregulation of retinal blood flow in newborn pig. Am J Physiol. 1995 Sep;269(3 Pt 2):H1065–H1072. doi: 10.1152/ajpheart.1995.269.3.H1065. [DOI] [PubMed] [Google Scholar]
  11. Granstam E., Wang L., Bill A. Vascular effects of endothelin-1 in the cat; modification by indomethacin and L-NAME. Acta Physiol Scand. 1993 Jun;148(2):165–176. doi: 10.1111/j.1748-1716.1993.tb09546.x. [DOI] [PubMed] [Google Scholar]
  12. Grunwald J. E., DuPont J., Dreyer E. B. Effect of chronic nitrate treatment on retinal vessel caliber in open-angle glaucoma. Am J Ophthalmol. 1997 Jun;123(6):753–758. doi: 10.1016/s0002-9394(14)71123-7. [DOI] [PubMed] [Google Scholar]
  13. Haefliger I. O., Zschauer A., Anderson D. R. Relaxation of retinal pericyte contractile tone through the nitric oxide-cyclic guanosine monophosphate pathway. Invest Ophthalmol Vis Sci. 1994 Mar;35(3):991–997. [PubMed] [Google Scholar]
  14. Hoste A. M., Boels P. J., Brutsaert D. L., De Laey J. J. Effect of alpha-1 and beta agonists on contraction of bovine retinal resistance arteries in vitro. Invest Ophthalmol Vis Sci. 1989 Jan;30(1):44–50. [PubMed] [Google Scholar]
  15. Koss M. C. Role of nitric oxide in maintenance of basal anterior choroidal blood flow in rats. Invest Ophthalmol Vis Sci. 1998 Mar;39(3):559–564. [PubMed] [Google Scholar]
  16. Kramer M. S., Feinstein A. R. Clinical biostatistics. LIV. The biostatistics of concordance. Clin Pharmacol Ther. 1981 Jan;29(1):111–123. doi: 10.1038/clpt.1981.18. [DOI] [PubMed] [Google Scholar]
  17. Mann R. M., Riva C. E., Stone R. A., Barnes G. E., Cranstoun S. D. Nitric oxide and choroidal blood flow regulation. Invest Ophthalmol Vis Sci. 1995 Apr;36(5):925–930. [PubMed] [Google Scholar]
  18. O'Brien C., Kelly P. A., Ritchie I. M. Effect of chronic inhibition of nitric oxide synthase on ocular blood flow and glucose metabolism in the rat. Br J Ophthalmol. 1997 Jan;81(1):68–71. doi: 10.1136/bjo.81.1.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rassam S. M., Patel V., Brinchmann-Hansen O., Engvold O., Kohner E. M. Accurate vessel width measurement from fundus photographs: a new concept. Br J Ophthalmol. 1994 Jan;78(1):24–29. doi: 10.1136/bjo.78.1.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rassam S. M., Patel V., Kohner E. M. The effect of experimental hypertension on retinal vascular autoregulation in humans: a mechanism for the progression of diabetic retinopathy. Exp Physiol. 1995 Jan;80(1):53–68. doi: 10.1113/expphysiol.1995.sp003834. [DOI] [PubMed] [Google Scholar]
  21. Riva C. E., Grunwald J. E., Petrig B. L. Autoregulation of human retinal blood flow. An investigation with laser Doppler velocimetry. Invest Ophthalmol Vis Sci. 1986 Dec;27(12):1706–1712. [PubMed] [Google Scholar]
  22. Riva C. E., Sinclair S. H., Grunwald J. E. Autoregulation of retinal circulation in response to decrease of perfusion pressure. Invest Ophthalmol Vis Sci. 1981 Jul;21(1 Pt 1):34–38. [PubMed] [Google Scholar]
  23. Roufail E., Stringer M., Rees S. Nitric oxide synthase immunoreactivity and NADPH diaphorase staining are co-localised in neurons closely associated with the vasculature in rat and human retina. Brain Res. 1995 Jun 26;684(1):36–46. doi: 10.1016/0006-8993(95)00394-6. [DOI] [PubMed] [Google Scholar]
  24. Schmetterer L., Findl O., Fasching P., Ferber W., Strenn K., Breiteneder H., Adam H., Eichler H. G., Wolzt M. Nitric oxide and ocular blood flow in patients with IDDM. Diabetes. 1997 Apr;46(4):653–658. doi: 10.2337/diab.46.4.653. [DOI] [PubMed] [Google Scholar]
  25. Schmetterer L., Findl O., Strenn K., Graselli U., Kastner J., Eichler H. G., Wolzt M. Role of NO in the O2 and CO2 responsiveness of cerebral and ocular circulation in humans. Am J Physiol. 1997 Dec;273(6 Pt 2):R2005–R2012. doi: 10.1152/ajpregu.1997.273.6.R2005. [DOI] [PubMed] [Google Scholar]
  26. Schmetterer L., Krejcy K., Kastner J., Wolzt M., Gouya G., Findl O., Lexer F., Breiteneder H., Fercher A. F., Eichler H. G. The effect of systemic nitric oxide-synthase inhibition on ocular fundus pulsations in man. Exp Eye Res. 1997 Mar;64(3):305–312. doi: 10.1006/exer.1996.0213. [DOI] [PubMed] [Google Scholar]
  27. Schmetterer L., Wolzt M., Salomon A., Rheinberger A., Unfried C., Zanaschka G., Fercher A. F. Effect of isoproterenol, phenylephrine, and sodium nitroprusside on fundus pulsations in healthy volunteers. Br J Ophthalmol. 1996 Mar;80(3):217–223. doi: 10.1136/bjo.80.3.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Seligsohn E. E., Bill A. Effects of NG-nitro-L-arginine methyl ester on the cardiovascular system of the anaesthetized rabbit and on the cardiovascular response to thyrotropin-releasing hormone. Br J Pharmacol. 1993 Aug;109(4):1219–1225. doi: 10.1111/j.1476-5381.1993.tb13752.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Suzuki Y. Direct measurement of retinal vessel diameter: comparison with microdensitometric methods based on fundus photographs. Surv Ophthalmol. 1995 May;39 (Suppl 1):S57–S65. doi: 10.1016/s0039-6257(05)80074-8. [DOI] [PubMed] [Google Scholar]
  30. Zagvazdin Y. S., Fitzgerald M. E., Sancesario G., Reiner A. Neural nitric oxide mediates Edinger-Westphal nucleus evoked increase in choroidal blood flow in the pigeon. Invest Ophthalmol Vis Sci. 1996 Mar;37(4):666–672. [PubMed] [Google Scholar]

Articles from The British Journal of Ophthalmology are provided here courtesy of BMJ Publishing Group

RESOURCES