LOW-INTENSITY/HIGH-DENSITY SUBTHRESHOLD MICROPULSE DIODE LASER FOR CHRONIC CENTRAL SEROUS CHORIORETINOPATHY KHURRAM J. MALIK, MD, KAPIL M. SAMPAT, DO, AZAD MANSOURI, MD, JOSHUA N. STEINER, MD, BERT M. GLASER, MD Purpose: To evaluate the visual outcomes and macular thickness change in patients with symptomatic chronic central serous chorioretinopathy after treatment with a subthreshold MicroPulse diode laser. Methods: In this retrospective, interventional case series, 10 patients were treated with the subthreshold 810-nm diode MicroPulse laser. Selected patients had symptomatic disease that may or may not have involved the foveal center. The MicroPulse laser was applied to the areas of leakage seen on fluorescein angiogram, over the areas of clinical neurosensory detachment, and/or pigment epithelial detachments. Pretreatment and posttreatment vision, change in maximum macular thickness, number of treatment sessions, and number of laser spot applications were recorded. Patients were excluded if they did not attend follow-up, had other confounding macular diseases, were using steroid medications, or application of another treatment modality had been used (i.e., photodynamic therapy or anti-vascular endothelial growth factor medication). Results: Ten patients met the inclusion criteria, with 1 patient treated in both eyes. Three patients were excluded for lack of follow-up, one for the use of systemic steroids, and one for treatment with anti-vascular endothelial growth factor injection. Maximum macular thickness decreased after subthreshold MicroPulse laser treatment between 20 mm and 338 mm (mean = 97 mm decrease, P = 0.0046) in 11 treated eyes. Conclusion: Subthreshold diode MicroPulse laser is a potential treatment option for patients with symptomatic chronic central serous chorioretinopathy. RETINA 35:532–536, 2015

C

entral serous chorioretinopathy (CSCR) was first described by von Graefe1 in 1866 as “central recurrent retinitis.” Nearly 100 years later, Maumenee2 determined that the source of serous leakage originated from the level of the retinal pigment epithelium (RPE). Gass3 appropriately renamed the condition as CSCR in 1967. Central serous chorioretinopathy is characterized by neurosensory detachment with or without concomitant pigment epithelial detachment.4

Fluorescein angiography has helped identify the focal areas of RPE decompensation from which leakage of dye originates and then pools within the areas of detachment. Central serous chorioretinopathy remains an idiopathic disorder. Associations exist with extraocular conditions including Type A personality, use of exogenous steroids, Cushing disease, and systemic lupus erythematosus.5–7 Removing any identifiable factors that may cause or exacerbate the underlying CSCR is an initial priority. Many cases of CSCR resolve after a period of observation without any treatment.6 In refractory cases, treatment options have included focal laser treatment, photodynamic therapy, and intravitreal anti-vascular endothelial growth factor medications.8 Focal thermal laser photocoagulation at the site of presumed RPE decompensation (area of leakage on

From the National Retina Institute, Towson, Maryland. Paper presented as a poster titled “Subthreshold MicroPulse Diode Laser Is a Safe and Effective Modality to Treat Symptomatic Chronic Central Serous Chorioretinopathy” at ASRS 2013, Toronto, CA, August 27 and 28, 2013. None of the authors have any financial/conflicting interests to disclose. Reprint requests: Khurram J. Malik, MD, National Retina Institute, 901 Dulaney Valley Road, Suite 200, Towson, MD 21204; e-mail: [email protected]

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fluorescein angiogram) has been shown to promote resolution of the serous detachment in CSCR.9 Conventional laser applies a thermal burn to the retina and exposes the patient to risks of scotoma, long-term focal scar expansion, choroidal neovascularization, and potential new sites of leakage.10 Subthreshold MicroPulse (STMP) laser has been shown to avoid the risks of conventional laser with the potential of improving retinal edema in diabetic macular edema and branch retinal vein occlusion.11 Application of STMP laser in the setting of CSCR has been previously described.12–17 Some of these previous studies have used “test burns” and STMP laser with duty cycles of 15%. The use of both duty cycles have been documented by color fundus, infrared, and autofluorescence imaging to cause mild clinically visible RPE alterations secondary to local heating, despite “care” to avoid such changes.9 In our study, we investigate the efficacy of STMP laser at a predetermined laser power (750–1,000 mW) and lower duty cycle (5%) for the treatment of CSCR. The lower settings may allow for truly subvisible treatment sparing any RPE alteration as evaluated by clinical and diagnostic studies and also without the use of a test burn.9 We retrospectively reviewed the treatment effect of STMP laser in patients with symptomatic CSCR of at least 3 months of duration.

Germany) for eight patients and time domain OCT in three patients, the difference arising on availability in each clinic location. All patients were treated with a 810-nm diode MicroPulse laser (IRIDEX Corporation, Mountain View, CA). Seven patients were treated with the following laser settings: 950 mw, 5% duty cycle, and 0.3 seconds of pulse duration. Three patients differed with powers of 750, 900, and 1,000 mW used. Of these three patients, a shorter duration of 0.2 seconds of pulse duration was used in two patients. The pretreatment observation period varied between 2 months and 77 months with an average of 27.6 months. At follow-up, visual acuity assessment, macular OCT, and treatment responses were recorded (Table 1). Patients were considered for retreatment with STMP laser, if clinically significant subretinal fluid persisted after 3 months. Decision on the extent of laser application was determined by the physician performing the treatment based on the leakage pattern on fluorescein angiogram. In six eyes with a focal point of fluorescein leakage, STMP laser was limited to 1 disk diameter surrounding this area. In five eyes with fluorescein leakage without a defined focal leakage point, STMP laser was applied to the areas of serous elevation as determined by clinical examination and OCT evaluation.

Methods

Results

Institutional Review Board approval was obtained for the study from the Western Institutional Review Board, Olympia, WA. All data were collected in accordance with the Health Insurance Portability and Accountability Act of 1996. We retrospectively reviewed the office charts of patients with the diagnosis of CSCR treated with an 810-nm STMP laser from February 2012 to April 2013. Consecutive patients with symptomatic CSCR of 3 months or greater were offered STMP treatment. Patients with CSCR of ,2 months and those treated with conventional thermal laser, surgery, or intravitreal injection in the month before STMP laser treatment were excluded. In addition, patients with simultaneous retinal diseases affecting visual acuity such as age-related macular degeneration, vein occlusions, and epiretinal membranes were also excluded. Informed consent for focal laser treatment was obtained from all patients. Visual acuity was measured using the standard Early Treatment Diabetic Retinopathy Study (ETDRS) chart evaluation on all visits. Maximum macular thickness (MMT) was measured using the spectral domain optical coherence tomography (OCT) (Heidelberg,

There were 11 eyes of 10 patients that met the inclusion criteria and were treated with the 810-nm MicroPulse laser. One patient underwent treatment with STMP laser in both eyes. The posttreatment follow-up period in these eyes ranged from 2 months to 12 months. One patient required retreatment after 6 months for recurrent fluid. Mean ETDRS visual acuity before treatment was 39.2 letters (range, 8–58 letters; standard deviation = 15.1). Mean ETDRS visual acuity after treatment was 45.5 letters (range, 14–55 letters; standard deviation = 12.0). Mean baseline MMT was 414 mm (standard deviation = 137.0 mm). Maximum macular thickness on the final follow-up was 316.2 mm (standard deviation = 96.5). Change in MMT was an average decrease of 97.8 mm (range, −7 to 213 mm). Specifics of data are detailed in Table 1. In 7 of 11 cases (63.6%), the reduction in MMT was 88 mm or more, equivalent to $25% reduction compared with the initial presenting MMT. The overall effectiveness of STMP laser in inducing reduction of pretreatment MMT was evident in 8 of 11 included eyes (72.7%) after a single treatment session. Paired t-test comparing initial MMT with the final MMT after treatment

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RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES  2015  VOLUME 35  NUMBER 3 Table 1. Data Summary Length of Observation Period, Months

Initial VA (ETDRS letters)

VA at the Final Follow-up (ETDRS letters)

Change in VA (ETDRS letters)

Initial MMT, mm

Final MMT, mm

Change MMT, mm

1 2

5 77

39 51

52 50

13 −1

371 357

269 327

−102 −30

3

5

43

55

12

478

247

−231

4

12

53

50

−3

279

286

7

5 6 7 8 9 10 11

2 64 12 29 14 14 70

63 8 30 46 35 58 38

55 14 33 48 50 48 45

−8 6 3 2 15 −10 7

394 335 361 358 434 390 797

261 315 398 270 299 233 573

−133 −20 37 −88 −135 −157 −224

Patient (Eye)

Treatment Pattern Diffuse Focal and diffuse Focal and diffuse Focal and diffuse Focal Focal Focal Focal Focal Focal Diffuse

No. Laser Spots 657 306 242 94 237 527 85 488 170 166 630

ETDRS, Early Treatment Diabetic Retinopathy Study; VA, visual acuity.

with STMP laser demonstrated significance with P = 0.0046. Discussion Central serous chorioretinopathy is as an idiopathic disorder that may result in acute and chronic symptoms of blurred vision, anisometropia, and metamorphopsia. The natural history of CSCR results in normalization of symptoms and objective findings of serous retinal detachment in more than half of acute cases.17 A growing number of treatment options for chronic CSCR have been published, including low-dose methotrexate, halffluence photodynamic therapy, ketoconazole, and bevacizumab as an alternative to conventional direct focal laser treatment.18–24 Each of these treatment options has the potential to cause irreversible damage to the retina, choroid, or RPE, or systemic side effects. Bandello et al15 first reported MicroPulse diode laser as a treatment option for CSCR in an ARVO e-abstract in 2003—a modality that avoids both indirect and direct risks in treating symptomatic chronic CSCR. Subsequent publications, although few, have documented the utility of STMP laser for both subfoveal and extrafoveal serous retinal detachments for treatment of CSCR.12–14 In each of these studies, a test burn was used to titrate the power, and they used a 15% duty cycle to provide a low threshold of laser application. However, test burns to determine the appropriate power necessary to provide subthreshold laser application cause irreversible RPE damage and can become a new source of leakage or choroidal neovascularization growth.10 To our knowledge, our study is the first to use a lower duty cycle (5%) and does not use a test burn.

The long-term safety of STMP laser was described by Luttrull et al in his work on diabetic macular edema using a subvisible MicroPulse laser and standard laser settings (no test spot). The laser settings of Luttrull et al9 involve set parameters of 800 mW to 950 mW, 5% to 15% duty cycle, and 100 milliseconds to 300 milliseconds of pulse duration, and laser application in a confluent pattern over the areas of retinal thickening as determined by contact lens examination and OCT. In the study of Luttrull et al9, none of 168 eyes treated with a 5% duty cycle showed any evidence of RPE alteration or damage as determined by fundus autofluorescence or fluorescein angiography. In this study, we evaluated the effectiveness of STMP laser for treatment of CSCR using a 5% duty cycle and power ranging from 750 mW to 1,000 mW. None of 11 eyes showed any evidence of RPE damage using fundus autofluorescence or fluorescein angiography. No previous study had used a low duty cycle of 5% (nondestructive subthreshold laser) in treatment of CSCR.11–15 A recent publication by Roisman et al demonstrated the effectiveness and safety of STMP laser in treatment of chronic CSCR in a prospective, randomized double-blind shamcontrolled study of 15 patients. This study used test burns to determine threshold power before treatment and subsequently used a 15% duty cycle.25 Our results of 8 of 11 eyes demonstrating significant reduction in maximum retinal thickness are similar to those described using higher duty cycles of 10% to 15%.11–17 In our series of patients, low-intensity/ high-density STMP laser using a 5% duty cycle seems to be a safe and effective modality for treatment of chronic CSCR (Figure 1).

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response in these CSCR cases may similarly be due to under treatment. Our study was limited by the size of our study population and its retrospective nature. Future studies would best be conducted as a prospective study using safe established laser parameters. Our study suggests the need for future prospective studies to determine the effectiveness of 5% duty cycle, nondestructive STMP laser in both acute and chronic CSCR. Key words: MicroPulse, subthreshold, laser, central serous chorioretinopathy. References

Fig. 1. Case example demonstrating the effect of STMP laser on a 40year-old patient with decreased vision of .3 months. Initial presentation early (A) and late (B and C) FA document multiple “hot spots” secondary to CSCR. Two cuts from pretreatment OCT (D and E document pretreatment subretinal fluid). Areas circled in yellow (C) were treated with an 810-nm diode MicroPulse laser: 950 mW, 5% duty cycle, 300 milliseconds of duration, and 237 contiguous treated spots. Within 6 months after treatment, there was visual improvement of 8 letters, decrease in leakage on FA (F–H), and resolution of subretinal fluid on OCT (I–K). FA, fluorescein angiography.

It has been implicated that the only risk of STMP laser (using an 810-nm diode laser) is under treatment.24 A low-intensity/high-density grid pattern of treatment confluent over the affected retinal area is recommended in treatment of diabetic macular edema.24 In our study, one patient demonstrated recurrent fluid during the follow-up period. A review of laser treatment settings revealed under treatment at the initial laser session. The second laser session emphasized the recommended low-intensity/ high-density treatment, and the total number of laser applications was substantially increased from 402 to 657 applications over the same area with the same settings. No recurrence has been observed since the repeat treatment. Similarly, it is interesting to note that two of the cases that did not respond to the applied STMP laser (increased maximum retinal thickness on follow-up) had the least number of laser applications. Lavinksy et al26 described the importance of high-density laser application with STMP in maximizing response to treatment in diabetic macular edema. It may be postulated that the failure of

1. von Graefe A. Ueber central recidiverende retinitis. Graefes Arch Clin Exp Ophthalmol 1866;12:211–215. 2. Maumenee AE. Macular diseases clinical manifestations. Trans Am Acad Ophthalmol Otolaryngol 1965;69:605–613. 3. Gass JD. Pathogenesis of disciform detachment of the neuroepithelium. Am J Ophthalmol 1967;63:1–139. 4. Klais CM, Ober MD, Ciardella AP, Yanuzzi LA. Central serous chorioretinopathy. In: Ryan SJ. ed. Retina. Vol 2. Philadelphia, PA: Elsevier; 2006:1135–1161. 5. Carvalho-Recchia CA, Yannuzzi LA, Negrao S, et al. Corticosteroids and central serous chorioretinopathy. Ophthalmology 2002;109:1834–1837. 6. Wang M, Munch IC, Hasler PW, et al. Central serous chorioretinopathy. Acta Ophthalmol 2008;86:126–145. 7. Yannuzzi LA. Type A behavior and central serous chorioretinopathy. Trans Am Ophthalmol Soc 1986;84:799–845. 8. Yanuzzi LA. Laser Photocoagulation of the Macula: Central Serous Chorioretinopathy. Philadelphia, PA: JB Lippincott; 1989:3–12. 9. Luttrull JK, Sramek C, Palanker D, et al. Long-term safety, high-resolution imaging, and tissue temperature modeling of subvisible diode MicroPulse photocoagulation for retinovascular macular edema. Retina 2012;32:375–386. 10. Little HL. Complications of argon laser retinal photocoagulation: a five-year study. Int Ophthalmol Clin 1976;16:145–159. 11. Koss MJ, Beger I, Koch FH. Subthreshold diode laser MicroPulse photocoagulation versus intravitreal injections of bevacizumab in the treatment of central serous chorioretinopathy. Eye (Lond) 2012;26:307–314. 12. Gupta B, Elagouz M, McHugh D, et al. Micropulse diode laser photocoagulation for central serous chorioretinopathy. Clin Experiment Ophthalmol 2009;37:801–805. 13. Chen S, Hwang J, Tseng L, Lin C. Subthreshold diode MicroPulse photocoagulation for the treatment of chronic central serous chorioretinopathy with juxtafoveal leakage. Ophthalmology 2008;115:2229–2234. 14. Lanzetta P, Furlan F, Morgante L, et al. Nonvisible subthreshold MicroPulse diode laser (810 nm) treatment of central serous chorioretinopathy. A pilot study. Eur J Ophthalmol 2008;18:934–940. 15. Bandello F, Lanzetta P, Furlan F, Polita A. Nonvisible subthreshold MicroPulse diode laser treatment of idiopathic central serous chorioretinopathy. A pilot study. Invest Ophthal Vis Sci 2003;44:ARVO e-abstract 4858. 16. Ricci F, Missiroli F, Cerulli L. Indocyanine green dye enhanced MicroPulse diode laser: a novel approach to subthreshold RPE treatment in a case of central serous chorioretinopathy. Eur J Ophthalmol 2004;14:74–82.

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17. Ricci F, Missiroli F, Regine F, et al. Indocyanine green enhanced subthreshold diode laser MicroPulse photocoagulation treatment of chronic central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol 2009;247:597–607. 18. Kurup SK, Oliver A, Emanuelli A, et al. Low-dose methotrexate for the treatment of chronic central serous chorioretinopathy: a retrospective analysis. Retina 2012;32: 2096–2101. 19. Smretschnig E, Ansari-Shahrezaei S, Hagen S, et al. Half-fluence photodynamic therapy in chronic central serous chorioretinopathy. Retina 2013;33:316–323. 20. Golshahi A, Klingmuller D, Holz FG, Eter N. Ketoconazole in the treatment of central serous chorioretinopathy: a pilot study. Acta Ophthalmol 2010;88:576–581. 21. Lim JW, Kim MU. The efficacy of intravitreal bevacizumab for idiopathic central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol 2011;249:969–974.

22. Lim SJ, Roh MI, Kwon OW. Intravitreal bevacizumab injection for central serous chorioretinopathy. Retina 2010;30:100–106. 23. Artunay O, Yuzbasioglu E, Rasier R, et al. Intravitreal bevacizumab in treatment of idiopathic persistent central serous chorioretinopathy: a prospective, controlled clinical study. Curr Eye Res 2010;35:91–98. 24. Luttrull JK, Dorin G. Subthreshold diode MicroPulse laser photocoagulation as invisible retinal phototherapy for diabetic macular edema: a review. Curr Diabetes Rev 2012;8:274–284. 25. Roisman L, Magalhães FP, Lavinsky D, et al. MicroPulse diode laser treatment for chronic central serous chorioretinopathy: a randomized pilot trial. Ophthalmic Surg Lasers Imaging Retina 2013;44:465–470. 26. Lavinsky D, Cardillo JA, Melo LA Jr, et al. Randomized clinical trial evaluating mETDRS versus normal or high-density micropulse photocoagulation for diabetic macular edema. Invest Ophthalmol Vis Sci 2011;52:4314–4323.

high-density subthreshold microPulse diode laser for chronic central serous chorioretinopathy.

To evaluate the visual outcomes and macular thickness change in patients with symptomatic chronic central serous chorioretinopathy after treatment wit...
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