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ORIGINAL ARTICLE
Year : 2018  |  Volume : 5  |  Issue : 2  |  Page : 41-46

Comparative study between single session pattern short pulse laser and conventional pan-retinal photocoagulation regarding efficacy and macular thickening in patients with diabetic retinopathy


Department of Ophthalmology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Date of Web Publication19-Feb-2019

Correspondence Address:
Dr. Ahmed Mahmoud Abdel Hadi
Department of Ophthalmology, Faculty of Medicine, Alexandria University, Alexandria
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/erj.erj_13_18

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  Abstract 


Aim: The aim of this study is to compare the effect of pan-retinal photocoagulation (PRP) using short-pulse laser (SPL) performed in a single session and conventional laser, regardless of the number of spots, in terms of their effect on the progression of diabetic macular edema (DME) and efficacy of regression of signs in patients with proliferative and high-risk nonproliferative diabetic retinopathy (NPDR). Methods: A prospective comparative case series was carried out, in which eyes with a similar degree of severe nonPDR or high-risk PDR underwent four-session PRP using a conventional laser in one eye (Group a) and a single session SPL in the other eye (Group b). After the session, colored photographs were taken to show immediate laser reaction. A follow-up visit was scheduled at 6 weeks to detect any complication. Finally, fluorescein angiography and optical coherence tomography were repeated at 3 months to assess the efficacy of laser treatment and the remeasure the macular thickness. Best-corrected visual acuity (BCVA) was remeasured after 12 weeks and compared to the prelaser VA. Results: The 20 patients included had a mean age of 53.4 ± 6.4 years. All patients had hemoglobin A1c (HBA1c) ranging from 7.2 to 8.4 with a mean of 7.7 ± 0.5. Before PRP initiation, there was no statistically significant difference between the two groups as regards mean age, duration of DM, and mean HBA1c. The mean power of laser was 198.7 ± 13.26 mW and 393.2 ± 17.7 mW (P < 0 0001), the total energy delivered was 49.7 ± 11.4 mJ and 12.1 ± 5.3 mJ (P < 0 0001), and the number of spots were 1784.2 ± 89.7 and 2773.2 ± 159.2 (P < 0 0001) in the Conventional (Conv) group and SPL group, respectively. At the final follow-up visit at 12 weeks, there was no statistically significant difference regarding the mean central macular thickness (P = 0.84) and BCVA (P = 1.0). One eye from each group was diagnosed with persistent diabetic retinopathy activity at 12 weeks, for which intravitreal ranibizumab was given twice, 1 month apart. The FA was repeated 3 months later with the disappearance of signs of activity. Conclusion: The current study revealed that SPL in a single session is as effective as conventional laser-performed in the same patient with a similar degree of DR in both eyes-to cause regression of diabetic retinopathy signs without causing progression of DME. This was achieved with a total number of laser shots approximately 1.5 times the number in the conventional laser-treated eyes.

Keywords: Conventional laser pan retinal photocoagulation, diabetic macular edema progression, low fluence laser, short pulse laser


How to cite this article:
Hadi AM. Comparative study between single session pattern short pulse laser and conventional pan-retinal photocoagulation regarding efficacy and macular thickening in patients with diabetic retinopathy. Egypt Retina J 2018;5:41-6

How to cite this URL:
Hadi AM. Comparative study between single session pattern short pulse laser and conventional pan-retinal photocoagulation regarding efficacy and macular thickening in patients with diabetic retinopathy. Egypt Retina J [serial online] 2018 [cited 2019 Mar 22];5:41-6. Available from: http://www.egyptretinaj.com/text.asp?2018/5/2/41/252539




  Introduction Top


Pan-retinal photocoagulation (PRP) is recognized as a standard treatment of proliferative diabetic retinopathy (PDR).[1],[2] PRP for the treatment of ischemic lesions includes purposeful destruction of some photoreceptors, as well as other more superficial retinal layers.[3] Although retinal laser treatment decreases the risks of visual disturbance in patients with severe nonPDR (NPDR) and PDR, diabetic macular edema (DME) progression sometimes occurs after PRP.

Some reports showed that thermal burns from laser photocoagulation lead to the upregulation of the vascular endothelial growth factor (VEGF) and several inflammatory responses that may play an important role in the progression of DME after PRP.[4],[5]

Recently, the pattern low fluence laser systems was developed to deliver single applications of multiple laser burns in a shorter pulse duration of 10–30 ms.[6] This shorter pulse duration results in less destruction within the retina is less painful and offers better preservation of retinal sensitivity for the patient than the conventional laser.[7],[8],[9],[10]

However, the short pulse laser (SPL) requires a greater number of shots to complete the PRP than conventional laser because the expansion of laser scars of SPL is less.[8],[11] This larger number of spots could induce a more intraocular inflammatory response, and it may lead to more severe inflammation and worsening of DME after PRP, even in the setting of SPL. Thus, it is still questionable whether SPL with greater number of shots is a less-invasive treatment than conventional lasers for diabetic retinopathy patients.

We put forward a study to compare the effect of PRP using SPL performed in a single session and conventional laser, regardless of the number of spots, in terms of their effect on the progression of DME and regression of signs in patients with proliferative and high-risk nonPDR (nonPDR).


  Methods Top


A prospective comparative case series study was carried out after approval of the Institutional and Ethics Committee at the Faculty of Medicine, Alexandria University. Informed written consents were obtained from all patients for this specific procedure.

The inclusion criteria included were as follows: (1) age >18 years, (2) patients diagnosed with severe NPDR or PDR, (3) no history or clinical evidence of prior PRP and (4) follow-up for ≥6 months. The exclusion criteria included the following: (1) other retinal disease such as retinal vein occlusion or uveitis, (2) a history of the cataract surgery within 12 months and any other intraocular surgeries, including the vitrectomy at any time point before PRP, (3) a history of intraocular injection, and (4) simultaneous focal/grid macular laser photocoagulation, (5) intraocular pressure >22 mm Hg, (6) use of topical medications containing prostaglandin derivatives, and (7) vitreous hemorrhage.

Pretreatment, the patients were subjected to complete ophthalmic examination including best-corrected visual acuity (BCVA) with tumbling E charts converted to Logmar for statistical reasons. Fluorescein angiography (FA) and spectrum domain optical coherence tomography (Cirrus OCT, Carl Zeiss Meditec, Dublin, CA, USA) were performed during the same week before retinal laser treatment.

Severe NPDR was diagnosed if one or more quadrant has intraretinal microvascular abnormalities, two or more quadrants have venous beading, or four quadrants have 20 retinal hemorrhages. PDR was diagnosed if neovascularization of the disc, neovascularization elsewhere or preretinal hemorrhage were present.

Patients with a similar degree of severe nonPDR or high-risk PDR in both eyes underwent four-session PRP along 8 days using a conventional laser in one eye (Group a) and a single session SPL in the other eye (Group b) between January 2017 and January 2018.

All PRP procedures were performed in a semi-darkened room approximately 20 min after the eyes were pharmacologically dilated with 1% tropicamide and 2.5% phenylephrine.

All eyes were anesthetized with topical benoxinate drops. The treatment with conventional laser was divided into four sessions with each session 2 days apart from the previous one, covering the area around the vascular arcades as far anterior as possible beyond the equator with Volk Super Quad 160 contact lens (Volk Optical, Inc., Mentor, OH, USA). The Iridex IQ 577 (Iridex, Mountain View, Cal, United States) was the retinal photocoagulator.

For the conventional argon group (Conv group), the laser power was set to 200 mW and increased by 10–20 mW until a gray/white lesion was attained, the duration of exposure was 100 ms in yellow wavelength (577 nm), the coagulation spot size was adjusted to 200 μm with a space of one coagulation spot between each of the spots.

In the single session SPL, the laser parameters were as follows: (1) spot size of 200 μm, (2) pulse duration of 20 ms, (3) type of laser spot 5 × 5 and 4 × 4 multispot arrays, (4) burn intensity of 300 mW, increased until a gray/white lesion was attained, and (5) spacing of 500 μm. The Iridex IQ 577 (Iridex, Mountain View, Cal, United States) was also used for treatment in this group.

Laser Energy (J) for both groups was calculated which is equal to (Laser Power [W]) × (Exposure Duration [s]) × (Duty Factor [%/100]). Duty Factor is often 5%–15% when using MicroPulse mode, and is 100% when using continuous wave mode.[12]

Postsession, colored photograph to show immediate laser reaction were acquired. A follow-up visit was scheduled at 6 weeks to detect any complication. Finally, FFA and OCT were repeated at 3 months to assess the efficacy of laser treatment and to remeasure the macular thickness. BCVA was remeasured at the final follow-up visit after 12 weeks and compared to the prelaser VA.

All patients who had recurrence or persistence of neovascularization were instructed to receive salvage treatment, including additional laser and/or intravitreal injection of the anti-VEGF drug.

Statistical analyses

We carried out statistical analyses using SPSS version 23 (SPSS Inc., Chicago, IL, USA). The statistical significances between the groups were assessed using the Mann–Whitney test. Values were expressed as means ± standard deviation (SD). Differences were considered statistically significant at P < 0 05.


  Results Top


The current study included 20 patients diagnosed clinically and with FA to have a similar degree of either severe nonPDR or high-risk PDR in both eyes. All patients underwent four-session PRP along 8 days using a conventional laser (Group a) in one eye and a single session of SPL in the other eye (Group b).

In the study cohort, the age ranged from 42 to 65 years with a mean ± SD of 53.4 ± 6.4 years.

The duration since the first diagnosis with DM ranged from 9 to 25 years with a mean of 17.3 ± 4.7 years. Nine of our patients were males, whereas 11 were female. All patients had hemoglobin A1c ranging from 7.2 to 8.4 with a mean of 7.7 ± 0.5 and all patients were on insulin therapy.

Basic patient characteristics are provided in [Table 1]. All the included patients suffered from DME with 10 (50% of this group) patients in the conventional group suffering from focal edema, whereas the rest were diagnosed with multifocal edema. In this group, 12 eyes (60%) had center involving DME, whereas the rest the ME was noncenter involving. In the SMP group, 12 patients (60%) were diagnosed with focal DME, with the rest of cases (8 eyes, 40%) suffering from multifocal edema. Again in this group, the OCT was used to identify the number of eyes with center involving DME which reached 8 eyes (40%) with the rest of eyes in this group belonging to the noncentre involving ME category.
Table 1: Baseline characteristics at the time of registration

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Before PRP initiation, the pretreatment central macular thickness (CMT) was 298.6 ± 11.74 μm and 295.45 ± 12.08 μm in Group a, and Group b, respectively. There was no statistically significant difference between the two groups (P = 0.409). Similarly, the pretreatment vision was 0.29 ± 0.091 and 0.285 ± 0.067 in Group A and Group b, respectively, with no statistically significant difference between them (P = 0.844).

The mean power of laser was 198.7 ± 13.26 mW and 393.2 ± 17.7 mW (P < 0 0001), in the Conv group and SPL group, respectively. The total energy delivered was 49.7 ± 11.4 mJ in the conventional laser group (Group a) and 12.1 ± 5.3 mJ in the SPL Group (Group b) (P < 0 0001).

The number of spots was 1784.2 ± 89.7 and 2773.2 ± 159.2 in Group a and Group b, respectively, again with no statistical significant difference between the two groups (P < 0 0001). The pulse duration was preset to 100 ms in Group a and 20 ms in Group b.

After PRP completion the mean CMT and BCVA for both groups were checked at 12 weeks [Table 2]. There was no statistical significance difference regarding the mean CMT (P = 0.84) and BCVA (P = 1.0) [Figure 1].
Table 2: Summary of patients&z#39; findings after pan retinal photocoagulation

Click here to view
Figure 1: Right eye of a type 2 diabetic patients, 15 years since first diagnosed. A clinical diagnosis of severe non-proliferative diabetic retinopathy with normal pre-laser central macular thickness of 273 μ with mild macular ischemia, best corrected visual acuity: 0.3 Logmar (a). Immediately after single session of low fluence short-pulse laser, delivering 1750 shot, with 20 ms spot duration, and a 12 mJ total energy as indicated at the conclusion of the session (b). Fundus photo and FA done 3 months after the short-pulse laser session showing no activity or residual ischemic areas in the midperiphery, with slight increased central macular thickness to 281 μ but with stable best-corrected visual acuity of 0.3 Logmar (c)

Click here to view


One eye from each group was diagnosed with persistent diabetic retinopathy activity at 12 weeks [Figure 2] and [Figure 3] for which intravitreal ranibizumab was given twice, 1 month apart. The FA was repeated 3 months later with the disappearance of signs of activity.
Figure 2: A patient with type II diabetes mellitus for 25 years, left eye suffers high risk proliferative diabetic retinopathy with central macular thickness of 289 um (a). Immediately after pattern one session short-pulse laser, composed of 2205 shots having 26.5 mJ of total energy delivered to the retina, duration 20 ms (b). Three months after laser, FA shows persistent activity with extensive leakage from neovessels elsewhere and on the disc, central macular thickness 293 μ (c)

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Figure 3: Left eye of a type II diabetes mellitus patient, FA showing high risk proliferative diabetic retinopathy with central macular thickness of 212 (a) Three months after four sessions of conventional laser delivering 1400 shot in total, with a duration of 200 ms and a total energy delivered of 52.3 mJ. FA still shows persistent activity, with a stable central macular thickness of 211 μ (b)

Click here to view



  Discussion Top


In a study by Muqit et al., eyes with PDR treated with a single SPL using PASCAL demonstrated less increased total CMT after treatment, compared with conventional single spot delivered over multiple sessions.[11] In the latter study, the total number of spots was the same in both groups, indicating that SPL was effective in regression of PDR without causing worsening of DME in the same shot number range as conventional laser. However, it was recognized earlier that SPL requires a greater number of spots to attain control of DR, because the expansion of scars is less than that in the traditional laser.[8] The larger number of laser spots may cause worsening of DME. Therefore, we were interested to know whether SPL is a less-invasive treatment than traditional lasers, even if double the number of shots were performed for the management of PDR.

In the current data, the total number of spots in the SPL group was 1.5 times more than that in the Conv group. Yet, there was no statistically significant difference in the CMT 3 months postlaser between the two groups.

Similar to our results, Mirshahi et al. reported a significantly smaller increase in CMT after laser therapy in SPL group than in the conventional laser group.[13] In their study, the number of spots in the short pulse pattern laser group was approximately 1.4 times more than that in the conventional laser group. Hence, with a greater number of laser spots, SPL was able to prevent the worsening of DME after PRP in the patients with diabetic retinopathy.

The effect of photocoagulation can be studied through three interdependent parameters, including spot size, power, and pulse duration.[14] In the current study, the pulse duration was 100 ms and 20 ms and the average power intensity was 198.7 ± 13.26 mW and 393.2 ± 17.7 mW (P < 0 0001) in the Conv and SPL groups, respectively. The total energy delivered was 49.7 ± 11.4 mJ and 12.1 ± 5.3 mJ (P < 0 0001) in the Conv and SPL groups, respectively. Hence, although the number of laser spots in SPL group was greater than that in the Conv group, the total energy to which the eye was exposed in the Conv group (49.7 mJ) was 4 times higher than that in the SPL group (12.1 mJ). The higher energy of lasers delivered might result in the greater progression of macular edema in the DME patients treated with Conv laser for their diabetic retinopathy.

In the current case series, one eye from each group had persistent active diabetic retinopathy at 3 months postlaser, and no cases were complicated with vitreous hemorrhage in the two groups during the follow-up period. However, the observational periods are too short, and the sample size is too small to evaluate the exact efficacy of low fluence single session SPL in preventing complications in DR cases requiring laser therapy.


  Conclusion Top


The current study revealed that SPL performed in a single session is as effective as conventional laser-performed in the same patient with a similar degree of DR in both eyes to cause regression of diabetic retinopathy signs without causing progression of DME. This was achieved with a total number of laser shots approximately 1.5 times the number in the conventional laser-treated eyes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of diabetic retinopathy study (DRS) findings, DRS report number 8. The Diabetic Retinopathy Study Research Group. Ophthalmology 1981;88:583-600.  Back to cited text no. 1
    
2.
Argon laser scatter photocoagulation for prevention of neovascularization and vitreous hemorrhage in branch vein occlusion. A randomized clinical trial. Branch Vein Occlusion Study Group. Arch Ophthalmol 1986;104:34-41.  Back to cited text no. 2
    
3.
Paulus YM, Jain A, Gariano RF, Stanzel BV, Marmor M, Blumenkranz MS, et al. Healing of retinal photocoagulation lesions. Invest Ophthalmol Vis Sci 2008;49:5540-5.  Back to cited text no. 3
    
4.
Ito A, Hirano Y, Nozaki M, Ashikari M, Sugitani K, Ogura Y, et al. Short pulse laser induces less inflammatory cytokines in the murine retina after laser photocoagulation. Ophthalmic Res 2015;53:65-73.  Back to cited text no. 4
    
5.
Itaya M, Sakurai E, Nozaki M, Yamada K, Yamasaki S, Asai K, et al. Upregulation of VEGF in murine retina via monocyte recruitment after retinal scatter laser photocoagulation. Invest Ophthalmol Vis Sci 2007;48:5677-83.  Back to cited text no. 5
    
6.
Sanghvi C, McLauchlan R, Delgado C, Young L, Charles SJ, Marcellino G, et al. Initial experience with the Pascal photocoagulator: A pilot study of 75 procedures. Br J Ophthalmol 2008;92:1061-4.  Back to cited text no. 6
    
7.
Jain A, Blumenkranz MS, Paulus Y, Wiltberger MW, Andersen DE, Huie P, et al. Effect of pulse duration on size and character of the lesion in retinal photocoagulation. Arch Ophthalmol 2008;126:78-85.  Back to cited text no. 7
    
8.
Muqit MM, Gray JC, Marcellino GR, Henson DB, Young LB, Patton N, et al. In vivo laser-tissue interactions and healing responses from 20- vs. 100-millisecond pulse Pascal photocoagulation burns. Arch Ophthalmol 2010;128:448-55.  Back to cited text no. 8
    
9.
Muqit MM, Marcellino GR, Gray JC, McLauchlan R, Henson DB, Young LB, 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;94:1493-8.  Back to cited text no. 9
    
10.
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;31:1699-707.  Back to cited text no. 10
    
11.
Muqit MM, Marcellino GR, Henson DB, Young LB, Turner GS, Stanga PE, et al. Pascal panretinal laser ablation and regression analysis in proliferative diabetic retinopathy: Manchester Pascal Study Report 4. Eye (Lond) 2011;25:1447-56.  Back to cited text no. 11
    
12.
Venkatesh P, Ramanjulu R, Azad R, Vohra R, Garg S. Subthreshold micropulse diode laser and double frequency neodymium: YAG laser in treatment of diabetic macular edema: A prospective, randomized study using multifocal electroretinography. Photomed Laser Surg 2011;29:727-33.  Back to cited text no. 12
    
13.
Mirshahi A, Lashay A, Roozbahani M, Fard MA, Molaie S, Mireshghi M, et al. Pain score of patients undergoing single spot, short pulse laser versus conventional laser for diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2013;251:1103-7.  Back to cited text no. 13
    
14.
Muqit MM, Marcellino GR, Henson DB, Young LB, Patton N, Charles SJ, et al. Single-session vs. multiple-session pattern scanning laser panretinal photocoagulation in proliferative diabetic retinopathy: The Manchester Pascal Study. Arch Ophthalmol 2010;128:525-33.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

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