Correspondence

Diabetic Retinopathy

N Engl J Med 2004; 350:2525-2526June 10, 2004

Article

To the Editor:

In a review article on diabetic retinopathy (Jan. 1 issue),1 Frank stated that the mechanism for the effect of panretinal, or scatter, laser treatment on diabetic retinopathy is unclear. Two references, from 1978 and 1982, were cited to support this conclusion.

The review article ignores a substantial literature on the physiological mechanism of retinal laser treatment for proliferative diabetic retinopathy and diabetic macular edema, reviewed elsewhere.2 These works confirm that scattered laser photocoagulation increases the oxygen tension in the inner retina,3 alleviates hypoxia,4 and affects the hemodynamics of the retinal circulation.5 These studies have been carried out in several species of animals and confirmed in humans,2 contrary to the statement by Frank that intraocular oxygen electrodes cannot be used in humans.

Improved retinal oxygenation affects neovascularization and edema formation in diabetic retinopathy by means of the reduced production of (vascular endothelial) growth factors and hemodynamic changes according to Starling's law.2

Einar Stefánsson, M.D., Ph.D.
University of Iceland, 101 Reykjavik, Iceland
einarste@landspitali.is

5 References

1. 1

   Frank RN. Diabetic retinopathy. N Engl J Med 2004;350:48-58
   Full Text | Web of Science | Medline

2. 2

   Stefansson E. The therapeutic effects of retinal laser treatment and vitrectomy: a theory based on oxygen and vascular physiology. Acta Ophthalmol Scand 2001;79:435-440
   CrossRef | Medline

3. 3

   Stefansson E, Landers MB III, Wolbarsht ML. Increased retinal oxygen supply following pan-retinal photocoagulation and vitrectomy and lensectomy. Trans Am Ophthalmol Soc 1981;79:307-334
   Medline

4. 4

   Pournaras CJ, Tsacopoulos M, Strommer K, Gilodi N, Leuenberger PM. Scatter photocoagulation restores tissue hypoxia in experimental vasoproliferative microangiopathy in miniature pigs. Ophthalmology 1990;97:1329-1333
   Web of Science | Medline

5. 5

   Feke GT, Green GJ, Goger DG, McMeel JW. Laser Doppler measurements of the effect of panretinal photocoagulation on retinal blood flow. Ophthalmology 1982;89:757-762
   Web of Science | Medline

Author/Editor Response

Stefánsson notes that I have cited two references to support my claim that the mechanism for the effect of panretinal photocoagulation in proliferative diabetic retinopathy is unclear. These references were, in fact, among the earliest to suggest that retinal hypoxia is a prominent cause of retinal neovascularization. As long as this hypothesis has been extant, the beneficial effect of panretinal photocoagulation has been attributed to its reduction of hypoxia.1 Although it is widely accepted, here is why I think this hypothesis is not fully established.

First, panretinal photocoagulation dramatically reduces blindness that results from proliferative diabetic retinopathy, but the retinopathy progresses in some patients despite thousands of retinal laser burns that should largely ablate hypoxic retina.2 Second, other non–oxygen-regulated mechanisms also play important roles in the development of proliferative retinopathy.3 Third, in animal models of retinal neovascularization in which retinal oxygenation was measured, new vessels developed in less than 50 percent of the hypoxic regions.4,5 Because of the invasive nature of intraocular oxygen electrodes, their use during surgical procedures performed in humans must be very infrequent.

Robert N. Frank, M.D.
Kresge Eye Institute, Detroit, MI 48201
rnfrank@med.wayne.edu

5 References

1. 1

   Weiter JJ, Zuckerman R. The influence of the photoreceptor-RPE complex on the inner retina: an explanation for the beneficial effects of photocoagulation. Ophthalmology 1980;87:1133-1139
   Web of Science | Medline

2. 2

   Vine AK. The efficacy of additional argon laser photocoagulation for persistent, severe proliferative diabetic retinopathy. Ophthalmology 1985;92:1532-1537
   Web of Science | Medline

3. 3

   Smith LEH, Kopchick JJ, Chen W, et al. Essential role of growth hormone in ischemia-induced retinal neovascularization. Science 1997;276:1706-1709
   CrossRef | Web of Science | Medline

4. 4

   Zhang W, Ito Y, Berlin E, Roberts R, Berkowitz BA. Role of hypoxia during normal retinal vessel development and in experimental retinopathy of prematurity. Invest Ophthalmol Vis Sci 2003;44:3119-3123
   CrossRef | Web of Science | Medline

5. 5

   Pournaras CJ. Retinal oxygen distribution: its role in the physiopathology of vasoproliferative microangiopathies. Retina 1995;15:332-347
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Nancy M. Holekamp, Ying-Bo Shui, David Beebe. (2006) Lower Intraocular Oxygen Tension in Diabetic Patients: Possible Contribution to Decreased Incidence of Nuclear Sclerotic Cataract. American Journal of Ophthalmology 141:6, 1027-1032
   CrossRef