Aims: The purpose of this study was to evaluate the effect of pulse duration on the expression of inflammatory cytokines in the murine retina after laser photocoagulation treatment with a PASCAL® pattern scan laser photocoagulator and conventional laser treatment. Methods: Retinal scatter laser photocoagulation was performed on C57BL/6J mice using a short pulse (10 ms) with a PASCAL laser or conventional settings (100 ms) with a multicolor laser. Eyes were enucleated before treatment (control) and 1 day, 3 days and 7 days after treatment. The levels of inflammatory cytokines (i.e., VEGF, MCP-1, RANTES and IL-6) in the retina/choroid were quantified by an ELISA. The expression patterns of VEGF and macrophages (i.e., F4/80) in the retina/choroid were evaluated by immunohistochemistry. Results: The levels of RANTES, IL-6 and MCP-1 after PASCAL and conventional laser treatments were significantly elevated compared with controls (p < 0.05). Conventional laser treatment, but not PASCAL treatment, resulted in the up-regulation of VEGF. RANTES and IL-6 levels on day 1 and MCP-1 levels on day 3 in the sensory retina were also significantly up-regulated with conventional laser treatment compared with PASCAL treatment (p < 0.05). Immunohistochemical analysis showed that PASCAL treatment was associated with lower VEGF and F4/80 expression levels compared with conventional laser treatment. Conclusions: Our data suggested that the short pulse duration induced fewer inflammatory cytokines in the sensory retina compared with the conventional pulse duration. Short pulse laser photocoagulation with the PASCAL may prevent macular edema after panretinal photocoagulation.

1.
Ding J, Wong TY: Current epidemiology of diabetic retinopathy and diabetic macular edema. Curr Diab Rep 2012;12:346-354.
2.
Aiello LP, Avery RL, Arrigg PG, et al: Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994;331:1480-1487.
3.
Early Treatment Diabetic Retinopathy Study Research Group: Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Ophthalmology 1991;98:766-785.
4.
Early Treatment Diabetic Retinopathy Study Research Group: Early treatment diabetic retinopathy study design and baseline patient characteristics. ETDRS report number 7. Ophthalmology 1991;98:741-756.
5.
MacMeel JW, Trempe CL, Franks EB: Diabetic maculopathy. Trans Am Acad Ophthalmol Otolaryngol 1977;83:476-487.
6.
McDonald HR, Schatz H: Visual loss following panretinal photocoagulation for proliferative diabetic retinopathy. Ophthalmology 1985;92:388-393.
7.
Moss SE, Klein R, Klein BEK: The incidence of visual loss in a diabetic population. Ophthalmology 1988;95:1340-1348.
8.
Tsujikawa A, Kiryu J, Dong J, Yasukawa T, Suzuma I, Takagi H, Ogura Y: Quantitative analysis of diabetic macular edema after scatter laser photocoagulation with the scanning retinal thickness analyzer. Retina 1999;19:59-64.
9.
Shimura M, Yasuda K, Nakazawa T, Kano T, Ota S, Tamai M: Quantifying alterations of macular thickness before and after pan-retinal photocoagulation in patients with severe diabetic retinopathy and good vision. Ophthalmology 2003;110:2386-2394.
10.
Shimura M, Yasuda K, Nakazawa T, et al: Visual dysfunction after panretinal photocoagulation on patients with severe diabetic retinopathy and good vision. Am J Ophthalmol 2005;140:8-15.
11.
Blumenkranz MS, Yellachich D, Andersen DE, et al: Semiautomated patterned scanning laser for retinal photocoagulation. Retina 2006;26:370-376.
12.
Jain AT, Blumenkranz MS, Paulus Y, et al: Effect of pulse duration on size and character of the lesion in retinal photocoagulation. Arch Ophthalmol 2008;126:78-85.
13.
Paulus YM, Jain A, Gariano RF, Stansel BV, et al: Healing of retinal photocoagulation lesions. Invest Ophthalmol Vis Sci 2008;49:5540-5545.
14.
Kriechbaum K, Bolz M, Deak GG, Prager S, Scholda C, Schmidt-Erfurth U: High-resolution imaging of the human retina in vivo after scatter photocoagulation treatment using a semiautomated laser system. Ophthalmology 2010;117:545-551.
15.
Muqit MM, Gray JC, Marcellino GR, et al: In vivo laser-tissue interactions and healing responses from 20- vs 100-millisecond pulse Pascal photocoagulation burns. Arch Ophthalmol 2010;128:448-455.
16.
Muqit MM, Gray JC, McLauchian R, et al: Pain responses of Pascal 20 ms multi-spot and 100 ms single-spot panretinal photocoagulation: Manchester Pascal Study, MAPASS report 2. Br J Ophthalmol 2010;94:1493-1498.
17.
Muqit MM, Marcellino GR, Henson DB, Fenerty CH, Stanga PE: Randomized clinical trial to evaluate the effects of Pascal panretinal photocoagulation on macular nerve fiber layer: Manchester Pascal Study report 3. Retina 2011;31:1699-1707.
18.
Nagpal M, Marlecha S, Nagpal K: Comparison of laser photocoagulation for diabetic retinopathy using 532-nm standard laser versus multispot pattern scan laser. Retina 2010;30:452-458.
19.
Itaya M, Sakurai E, Nozaki M, et al: Upregulation of VEGF in murine retina via monocyte recruitment after retinal scatter laser photocoagulation. Invest Ophthalmol Vis Sci 2007;48:5677-5683.
20.
Funatsu H, Noma H, Mimura T, et al: Association of vitreous inflammatory factors with diabetic macular edema. Ophthalmology 2009;116:73-79.
21.
Yoshimura T, Sonoda K, Sugahara M, et al: Comprehensive analysis of inflammatory immune mediators in vitreoretinal diseases. PloS One 2009;4:e8158.
22.
Ogata N, Ando A, Uyama M, Matsumura M: Expression of cytokines and transcription factors in photocoagulated human retinal pigment epithelial cells. Graefes Arch Clin Exp Ophthalmol 2001;239:87-95.
23.
Er H, Doganay S, Turkoz Y, et al: The levels of cytokines and nitric oxide in rabbit vitreous humor after retinal laser photocoagulation. Ophthalmic Surg Lasers 2000;31:479-483.
24.
Shimura M, Yoshida K, Nakazawa T, et al: Panretinal photocoagulation induces pro-inflammatory cytokines and macular thickening in high-risk proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2009;247:1617-1624.
25.
Shimura M, Yasuda K, Shiono T: Posterior sub-Tenon's capsule injection of triamcinolone acetonide prevents panretinal photocoagulation-induced visual dysfunction in patients with severe diabetic retinopathy and good vision. Ophthalmology 2006;113:381-387.
26.
Unoki N, Nishijima K, Kita M, et al: Randomised controlled trial of posterior sub-Tenon triamcinolone as adjunct to panretinal photocoagulation for treatment of diabetic retinopathy. Br J Ophthalmol 2009;93:765-770.
27.
Shimura M, Nakazawa T, Yasuda K, et al: Comparative therapy evaluation of intravitreal bevacizumab and triamcinolone acetonide on persistent diffuse diabetic macular edema. Am J Ophthalmol 2008;145:854-861.
28.
Nonaka A, Kiryu J, Tsujikawa A, et al: Inflammatory response after scatter laser photocoagulation in nonphotocoagulated retina. Invest Ophthalmol Vis Sci 2002;43:1204-1209.
29.
Izumi-Nagai K, Nagai N, Ohgami K, et al: Inhibition of choroidal neovascularization with an anti-inflammatory carotenoid astaxanthin. Invest Ophthalmol Vis Sci 2008;49:1679-1685.
30.
Fujimoto T, Sonoda KH, Hijioka K, et al: Choroidal neovascularization enhanced by Chlamydia pneumoniae via Toll-like receptor 2 in the retinal pigment epithelium. Invest Ophthalmol Vis Sci 2010;51:4694-4702.
31.
Crane IJ, Wallace CA, McKillop-Smith S, Forrester JV: Control of chemokine production at the blood-retina barrier. Immunology 2000;101:426-433.
32.
Muqit MM, Marcellino GR, Henson DB, Young LB, Turner GS, Stanga PE: Pascal panretinal laser ablation and regression analysis in proliferative diabetic retinopathy: Manchester Pascal Study Report 4. Eye (Lond) 2011;25:1447-1456.
33.
Muqit MM, Gray JC, Marcellino GR, et al: Fundus autofluorescence and Fourier-domain optical coherence tomography imaging of 10 and 20 millisecond Pascal retinal photocoagulation treatment. Br J Ophthalmol 2009;93:518-525.
34.
Chappelow AV, Tan K, Waheed NK, Kaiser PK: Panretinal photocoagulation for proliferative diabetic retinopathy: pattern scan laser versus argon laser. Am J Ophthalmol 2012;153:137-142.
35.
Panda-Jonas S, Jonas JB, Jakobczyk M, Schneider U: Retinal photoreceptor count, retinal surface area, and optic disc size in normal human eyes. Ophthalmology 1994;101:519-523.
36.
Remtulla S, Hallett PE: A schematic eye for the mouse, and comparisons with the rat. Vision Res 1985;25:21-31.
37.
Ferris FL 3rd, Podgor MJ, Davis MD: Macular edema in Diabetic Retinopathy Study patients. Diabetic Retinopathy Study Report Number 12. Ophthalmology 1987;94:754-760.
38.
Muqit MM, Marcellino GR, Henson DB, Young LB, Patton N, Charles SJ, Turner GS, Stanga PE: Single-session vs multiple-session pattern scanning laser panretinal photocoagulation in proliferative diabetic retinopathy: The Manchester Pascal Study. Arch Ophthalmol 2010;128:525-533.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.