Graefes Arch Clin Exp Ophthalmol DOI 10.1007/s00417-015-2965-7
RETINAL DISORDERS
Short-term efficacy of subthreshold micropulse yellow laser (577-nm) photocoagulation for chronic central serous chorioretinopathy Ju Young Kim & Han Sang Park & Si Yeol Kim
Received: 27 November 2014 / Revised: 30 January 2015 / Accepted: 4 February 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Purpose To investigate the short-term efficacy of subthreshold micropulse yellow laser photocoagulation in the treatment of chronic central serous chorioretinopathy (CSC). Methods A retrospective case series study was performed from April 2012 to June 2014 at Nune Eye Hospital. A total of ten eyes of ten chronic or chronic recurrent CSC patients received subthreshold micropulse yellow laser photocoagulation with a 15 % duty cycle at a reduced energy level from the micropulse laser test burn. Laser exposure time was 20 ms, and the spot diameter was 100 μm. Patients were followed up at the authors’ hospital for at least 3 months. Results Mean age of patients was 43.9 years. The baseline best-corrected visual acuity was 0.21±0.21 logarithm of the minimum angle of resolution (logMAR), which was improved to 0.055±0.093 logMAR (p=0.020) at the 3-month followup and 0.035±0.063 logMAR (p=0.012) at final follow-up. Central macular thickness at baseline was 349.2±53.2 μm, which was changed to 250.7±28.8 μm (p=0.009) at the 3month follow-up and 261.2±38.31 μm (p=0.009) at final follow-up. Conclusions Subthreshold micropulse yellow laser photocoagulation showed short-term efficacy in treating chronic CSC without retinal damage. However, prospective, randomized, and comparative large-scale studies are needed to evaluate the efficacy and safety of this treatment.
Keywords Central serous chorioretinopathy . Subthreshold micropulse yellow laser photocoagulation J. Y. Kim : H. S. Park : S. Y. Kim (*) Nune Eye Hospital, 18-21F LIG Bldg, 2397, Dalgubeol-daero, Suseong-gu, Daegu, Republic of Korea e-mail: [email protected]
Introduction Central serous chorioretinopathy (CSC) was first described in 1866 by Albrecht von Graefe, who named it ‘relapsing central luetic retinitis’ [1]. In 1967, Gass suitably renamed the condition as CSC [2]. CSC is a chorioretinal disorder, incompletely understood, that has systemic associations, multifactorial etiology, and complex pathogenesis. It typically affects young to middle-aged men, and is characterized by serous detachment of the neurosensory retina, which is usually located at the posterior pole [3]. The natural course of this disease is relatively benign. However, some patients with frequent recurrences or chronic neurosensory retinal detachment may develop retinal pigment epithelium (RPE) atrophy and neurosensory retinal atrophic changes, resulting in permanent loss of visual function, including visual acuity, color vision, and contrast sensitivity [4–7]. In these chronic or recurrent cases, treatment options include focal laser treatment, photodynamic therapy (PDT), and intravitreal anti-vascular endothelial growth factor (VEGF) medications [8]. Focal laser photocoagulation is commonly used to expedite the absorption of subretinal fluid (SRF) in acute and chronic CSC. Some reports have indicated that laser treatment was associated with a decreased rate of recurrences. However, this remains controversial [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 (CNV), and potential new sites of leakage [8]. Verteporfin PDT has shown promise by not only promoting resolution of acute CSC, but also preventing recurrences. Studies in chronic disease have yielded favorable results as well [10–13]. However, PDT has side-effects, such as choroidal ischemia, RPE atrophy, iatrogenic CNV, and RPE rip [14–17]. Intravitreal anti-VEGF injections are considered adjuvant treatments for CSC. Many studies have demonstrated
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anatomic and functional improvement following intravitreal anti-VEGF injection [18–22]. But Bae and colleagues reported the overall superiority of low-fluence PDT compared to intravitreal ranibizumab injection in the treatment of chronic CSC [23, 24], Currently, anti-VEGF agents are not considered as first-line treatment of chronic CSC.[9] Advances in laser technology have led to the development of selective photocoagulation for RPE via the subthreshold micropulse (STMP) laser photocoagulation method. 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 [25]. Application of STMP diode laser in the setting of CSC has been previously described [8, 25–29]. A new semiconductor laser device now provides solid-state 577-nm yellow laser light. Because this subthreshold micropulse yellow laser (SMYL) system was recently commercialized, no clinical studies of this system for chronic CSC have been reported to date. This 577-nm yellow laser system (Supra 577Y Laser System; Quantel Medical, ClermontFerrand, France) has been used for retinal treatment in our clinic since April 2011. The purpose of this retrospective study was to evaluate the short-term effect of subthreshold micropulse yellow laser photocoagulation (SMYLP) on eyes with chronic CSC using this laser system.
Fig. 1 Fluorescein angiography of a 31-year-old male patient (patient no. 7) and a 47-year-old male patient (patient no. 8). On fluorescein angiography, the no. 7 case has a definite leaking point near the fovea (a: early phase, b: late phase), and in the no. 8 case, a diffuse leaking pattern was observed (c: early phase, d: late phase)
Materials and methods We performed a retrospective case series study of ten eyes from ten patients who underwent SMYLP for chronic or chronic recurrent CSC at Nune Eye Hospital (Daegu, Korea) from April 2012 to June 2014. This study adhered to the ethical standards in the Declaration of Helsinki. Inclusion criteria were: symptomatic CSC of 6 months or greater, recurrent CSC patients with a history of chronic CSC, and patients who had received SMYLP for CSC treatment. Exclusion criteria were: (1)patients who had a history of another macular disease history such as age-related macular degeneration, retinal vascular occlusion, diabetic retinopathy, or epiretinal membrane, (2) patients who had received antiVEGF treatment (ranibizumab or bevacizumab), conventional thermal laser, intraocular surgery, or PDT in the past 3 months before and during SMYLP treatment, or (3) patients who were not followed up over 3 months after the start of SMYLP treatment. All patients received comprehensive ophthalmic examinations, including anterior segment examination and dilated biomicroscopic fundus examination. Best-corrected visual acuity (BCVA) was determined using a Snellen visual acuity (VA) chart. BCVA was converted to logarithm of the minimum angle of resolution (logMAR) units for statistical
1
1
40/M 42/M 47/M 44/M 40/M 44/M 31/M 47/M 52/M 52/M 1 2 3 4 5 6 7 8 9 10
F/U follow-up, BCVA best-corrected visual acuity, logMAR logarithm of the minimum angle of resolution, CMT central macular thickness, M male; NDL no definite leaking point
1,224 1,008 513 306 900 3,708 198 3,960 2,637 1,971 256 273 244 272 266 199 219 300 334 249 243 274 244 272 263 199 218 300 245 249 328 315 350 279 326 380 395 285 385 449 0 0.15 0 0 0 0 0 0.05 0.15 0 0 0.3 0 0 0 0.05 0.05 0.05 0.1 0 0.15 0.3 0.4 0.1 0.15 0.7 0.1 0 0.2 0 2 1 1 1 1 2 1 4 4 2 5 6 3 10 11 18 11 3 10 3
Age/sex
Table 1
We performed a retrospective study of ten eyes from ten patients with chronic or chronic recurrent CSC. All patients were male with mean age at diagnosis of 43.9±6.24 years (range, 31–52 years). There were three patients who had received previous anti-VEGF treatments before SMYLP treatment. Only one case had received a previous conventional focal
Data summary
Results
Patient (eye)
Distance between leaking point and foveal center, μm
Post treatment F/U period, months
No. initial treatment session
No. retreatment session for recurrent case
Initial BCVA (logMAR)
BCVA at 3 months (logMAR)
BCVA at the final F/U (logMAR)
Initial CMT, μm
3 months CMT, μm
Final CMT, μm
analysis. Color fundus photography and fluorescein angiography (Spectralis HRA; Heidelberg Engineering; Heidelberg, Germany) were performed before SMYLP treatment. Spectral-domain optical coherence tomography (SD-OCT) (Spectralis OCT; Heidelberg Engineering) was performed before SMYLP as well as during every follow-up visit. All treatments were provided by a single practitioner (H.S. Park) with the 577-nm yellow laser system (Supra 577Y Laser System). Laser application was performed with an AreaCentralis lens (Volk Optical, Mentor, OH, USA). Micropulse laser power used in SMYLP was derived for each eye from a test burn. Subthreshold treatment was performed in the micropulse mode, using a 100-μm spot diameter and a 20ms duration with 15 % duty cycle. An energy level below the threshold was used for a test burn. A single threshold burn was made in micropulse mode, and then the laser power reduced 50 % from the power of a single threshold burn, so that no visible retinal changes were made. In most cases, laser was applied in the energy level from 250~350 mW. Laser shots were delivered together in a 3×3 pattern mode (1.0 widths) over the entire area of CSC, including the leaking point on fluorescein angiogram and the foveal center. We also applied micropulse yellow laser on the normal retina around the borderline area of serous retinal detachment. At follow-up, BCVA assessment, macular OCT, and treatment responses were recorded. If the SRF was not completely resolved in a month after laser application, SMYLP was repeated until the SRF was completely resolved with monthly treatment pattern. Recurred CSC patients received SMYLP retreatment. We mainly observed the mean BCVA change and change of central macular thickness (CMT) over time as assessed by image-tracked Heidelberg Spectralis OCT volume scans from baseline to 3 months after SMYLP treatment and final followup. We also checked the mean choroidal thickness change assessed by enhanced depth imaging OCT (EDI-OCT) technique until final follow-up. The number of recurring CSC cases after SMYLP, and the incidence of adverse events were counted. Data were presented as mean±standard deviation. The post-treatment values were compared with the baseline values using the Wilcoxon signed-rank test. Statistical analyses were performed using SPSS ver. 18.0 (SPSS Inc., Chicago, IL, USA). Statistical significance was considered when p-value was less than 0.05.
397 375 790–1,421 NDL 2,990 NDL 1,606 NDL NDL 1,316
No. total laser spots
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laser treatment. There was no case that received previous PDT. The mean pre-SMYLP treatment follow-up period was 14.5± 8.3 months (range, 6–24 months). On fluorescein angiography, four cases have a diffuse leaking pattern, and in six cases, definite leaking points were observed. The mean distance between the leaking point and foveal center is 1,271 μm (Fig. 1). Specifics of data are summarized in Table 1. The findings for a 31-year-old man who underwent successful SMYLP are presented in Fig. 2. The mean post-SMYLP treatment follow-up period was 8 ±4.88 months (range, 3–18 months). The mean number of treatment sessions, including initial treatment and retreatment, was 2.1±1.45 (range, 1–5). The mean number of total laser shots was 1642.5±1374.84 (range, 198–3,960). There were two patients who had recurrent CSC. One recurrent case (patient no. 6) occurred at 6 months after the initial SMYLP treatment. Another case (patient no. 9) occurred at 10 months after the initial SMYLP treatment (Fig. 3). These two patients received SMYLP retreatment. One of these patients (patient no. 6) responded to retreatment, but the other patient (patient
no. 9) did not visit the next follow-up after retreatment. One case (patient no. 8) had persistent SRF for 3 months despite a total of four treatment sessions. Mean BCVA before treatment was 0.21±0.21 (range, 0–0.7 logMAR). Mean BCVA at 3 months after treatment was 0.055 ±0.093 (range, 0–0.3 logMAR). Mean BCVA at final followup was 0.035±0.063 (range, 0–0.15 logMAR). The BCVA was improved with statistical significance at 3 months (p=0.020) and at final follow-up (p=0.012) after the initial SMYLP treatment. Mean CMT before treatment was 349.2±53.22 μm (range, 279–449 μm). Mean CMT at 3 months after treatment was 250.7±28.79 μm (range, 199–300 μm). Mean CMT at final follow-up was 261.2±38.31 μm (range. 199–334 μm). CMT was decreased with statistical significance at 3 months (p=0.009) and at final follow-up (p=0.009) after the initial SMYLP treatment. Mean choroidal thickness before treatment was 398.7±87.02 μm (range, 276–525 μm). Mean choroidal thickness at 3 months after treatment was 400.5±93.52 μm (range, 274–525.7 μm). Mean choroidal thickness at final follow up was 399.8±99.35 μm (range, 260–529.7 μm). The
Fig. 2 Fundus photo, near infra-red images and spectral-domain optical coherence tomography images of the macula of a 31-year-old male patient (patient no. 7). Right eye before subthreshold micropulse yellow
laser photocoagulation (SMYLP) treatment (a, b), 3 months after SMYL P treatment (c, d), and 11 months after SMYLP treatment (e, f)
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choroidal thickness did not change with statistical significance at 3 months (p=0.878) or at final follow-up (p=0.859) after the initial SMYLP treatment. When before and after fundus color photographs, SD-OCT, and near infra-red images were compared, no laser scar was detected in color fundus photographs, SD-OCT, or near infrared images.
Discussion CSC can be classified into acute and chronic forms [3]. The natural course of acute CSC is believed to be very good, with primary cases being resolved spontaneously in 3 to 4 months [30, 31]. However, some patients are known to be associated with recurrent or persistent detachments. In these cases, the disorder is referred to as chronic CSC, which is arbitrarily defined as detachments lasting 6 months or longer [32]. Chronic CSC can result in diffuse RPE damage. These patients have long-standing SRF that cannot be reabsorbed efficiently because of choroidal disease and extensive dysfunction and loss of RPE. The presence of chronic SRF can lead to photoreceptor death, which can result in permanent visual loss. Furthermore, chronic CSC is likely to be complicated by CNV that can cause severe visual loss [9]. Not all patients with CSC have the chronic form. The reasons for Fig. 3 Fundus photo, near infrared images and spectral-domain optical coherence tomography images of the macula of a 52year-old male patient (patient no. 9). Right eye before subthreshold micropulse yellow laser photocoagulation (SMYLP) treatment (a, b), 3 months after SMYLP treatment (c, d), and 10 months after SMYLP treatment (e, f). He received SMYLP retreatment at 10 months after the initial treatment, but he didn’t visit at the next follow-up
varied courses are not well understood. The pathophysiology of CSC remains poorly understood despite advances in imaging techniques and many studies on this disease. Multiple etiologies and mechanisms that ultimately lead to choroidal circulation abnormalities have been suggested [33]. Hyperdynamic choroidal circulation and choroidal vascular hyperpermeability are the main features shared by patients with CSC [34]. Thermal laser photocoagulation for treating of CSC was based on the observation that a conventional laser photocoagulation of a fluorescein-detectable pigment epithelial leak may accelerate resolution of the associated neurosensory detachment [3, 9, 30, 35]. However, if the area of leakage is subfoveal or juxtafoveal, photocoagulation may induce secondary CNV and/or of damage to foveal photoreceptors. Several studies showed that no difference in final VA or in recurrence rate between eyes treated with argon laser photocoagulation and untreated eyes in long-term followed-up CSC patients [36]. Micropulse diode laser treatment targets a series of ultrashort 810 nm laser pulses at the tissue of interest. These repetitive bursts allow lower total energy use and help minimize damage to surrounding tissues from harmful thermal effects [37]. Retina-sparing photocoagulation is of particular interest in CSC. Bandello and colleagues first reported micropulse diode laser as a treatment option for CSC to avoid risks of
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harmful thermal events in treating symptomatic chronic CSC [38]. Subsequently, Chen and colleagues reported a series of 26 eyes of 25 patients in which 14 of 15 eyes with focal leaks had SRF resorption; only five of 11 eyes with diffuse leakage cleared all fluid. They concluded that STMP laser was effective in the treatment of CSC with point source leakage [26]. Ricci and colleagues have reported a series of seven eyes with persistent SRF, all of which were fluid-free at 1 year post STMP treatment [12, 29]. Recently, Malik and colleagues reported a retrospective case series study in which eight of 11 eyes after a single treatment session had decreased maximum macular thickness [8]. In short, 810-nm diode STMP laser is a potential treatment option as a safe treatment modality for patients with chronic CSC. Recently, a new 577-nm SMYLP device (Supra 577Y Laser System; Quantel Medical, Clermont-Ferrand, France) was introduced. Theoretically, the 577-nm yellow laser light provides peak absorption of oxyhemoglobin, excellent lesion visibility, low intraocular light scattering and pain, and negligible xanthophyll absorption [39, 40]. This leads to energy being concentrated in a smaller volume, which in turn allows for a reduction in power and shortened pulse duration. Additionally, the 577-nm yellow laser wavelength has the advantage of being better absorbed by melanin than the 810-nm laser wavelength, a characteristic that is theoretically suited to micropulse technique aimed at RPE cells. To our knowledge, this study is the first study on the efficacy and safety of 577-nm SMYLP treatment for chronic CSC. In this study, 577-nm SMYLP for chronic CSC showed good short-term clinical effect for improving BCVA and CMT. The second finding of our study was that SMYLP did not cause any chorioretinal damage in the human eye despite repeated micropulse laser treatments (shown by color fundus photographs, near infra-red photographs, and SD-OCT images, although these images can overlook microstructural chorioretinal damage). However, two cases had recurrent CSC and one case had persistent SRF. We found no significant choroidal thickness change assessed by EDI-OCT technique. These findings suggest that SMYLP for chronic CSC is effective and safe. However, this treatment modality may not prevent the recurrence of CSC perfectly. Maybe SMYLP only affects the RPE dysfunction without influencing the hyperdynamic choroidal circulation and choroidal hyper-permeability that have been thought the primary cause of CSC. Further study is needed to determine how SMYLP works in CSC. This study has several limitations. It was a small-sized retrospective case series study with an irregular follow-up period without a control group. Furthermore, we did not have a detailed standard treatment protocol and procedure guideline, including laser power setting, precise indications of retreatment, follow-up plan, and retreatment plan. Therefore, our data should be interpreted with caution. However, this study provide information for further study.
In conclusion, we suggest SMYLP may be one of the treatment options for chronic CSC. SMYLP may be effective as conventional laser treatment but safer than conventional laser photocoagulation and PDT. Prospective, randomized, largescale, long-term follow-up studies will be required to further evaluate the therapeutic efficacy and safety of SMYLP treatment for chronic CSC. Conflict of interest No potential conflict of interest relevant to this article was reported.
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serous chorioretinopathy with juxtafoveal leakage. Ophthalmology 115:2229–2234 27. Lanzetta P, Furlan F, Morgante L, Veritti D, Bandello F (2008) Nonvisible subthreshold micropulse diode laser (810 nm) treatment of central serous chorioretinopathy. A pilot study. Eur J Ophthalmol 18:934–940 28. Gupta B, Elagouz M, McHugh D, Chong V, Sivaprasad S (2009) Micropulse diode laser photocoagulation for central serous chorioretinopathy. Clin Exp Ophthalmol 37:801–805 29. Ricci F, Missiroli F, Regine F, Grossi M, Dorin G (2009) Indocyanine green enhanced subthreshold diode-laser micropulse photocoagulation treatment of chronic central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol 247:597–607 30. Gass JD (1977) Photocoagulation treatment of idiopathic central serous choroidopathy. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol 83:456–467 31. Yannuzzi LA (1986) Type A behavior and central serous chorioretinopathy. Trans Am Ophthalmol Soc 84:799–845 32. Yannuzzi LA (2010) Central serous chorioretinopathy: a personal perspective. Am J Ophthalmol 149:361–363 33. Spaide RF, Goldbaum M, Wong DW, Tang KC, Iida T (2003) Serous detachment of the retina. Retina 23:820–846, quiz 895-896 34. Guyer DR, Yannuzzi LA, Slakter JS, Sorenson JA, Ho A, Orlock D (1994) Digital indocyanine green videoangiography of central serous chorioretinopathy. Arch Ophthalmol 112:1057–1062 35. Ross A, Ross AH, Mohamed Q (2011) Review and update of central serous chorioretinopathy. Curr Opin Ophthalmol 22:166–173 36. Gemenetzi M, De Salvo G, Lotery AJ (2010) Central serous chorioretinopathy: an update on pathogenesis and treatment. Eye (Lond) 24:1743–1756 37. Sivaprasad S, Elagouz M, McHugh D, Shona O, Dorin G (2010) Micropulsed diode laser therapy: evolution and clinical applications. Surv Ophthalmol 55:516–530 38. Bandello F, Lanzetta P, Furlan F, Polita A (2003) Nonvisible subthreshold MicroPulse diode laser treatment of idiopathic central serous chorioretinopathy. A pilot study. Invest Ophthalmol Vis Sci 44: ARVO e abstract 4858 39. Mainster MA (1986) Wavelength selection in macular photocoagulation. Tissue optics, thermal effects, and laser systems. Ophthalmology 93:952–958 40. Mainster MA (1999) Decreasing retinal photocoagulation damage: principles and techniques. Semin Ophthalmol 14:200–209
RETINAL DISORDERS
Short-term efficacy of subthreshold micropulse yellow laser (577-nm) photocoagulation for chronic central serous chorioretinopathy Ju Young Kim & Han Sang Park & Si Yeol Kim
Received: 27 November 2014 / Revised: 30 January 2015 / Accepted: 4 February 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Purpose To investigate the short-term efficacy of subthreshold micropulse yellow laser photocoagulation in the treatment of chronic central serous chorioretinopathy (CSC). Methods A retrospective case series study was performed from April 2012 to June 2014 at Nune Eye Hospital. A total of ten eyes of ten chronic or chronic recurrent CSC patients received subthreshold micropulse yellow laser photocoagulation with a 15 % duty cycle at a reduced energy level from the micropulse laser test burn. Laser exposure time was 20 ms, and the spot diameter was 100 μm. Patients were followed up at the authors’ hospital for at least 3 months. Results Mean age of patients was 43.9 years. The baseline best-corrected visual acuity was 0.21±0.21 logarithm of the minimum angle of resolution (logMAR), which was improved to 0.055±0.093 logMAR (p=0.020) at the 3-month followup and 0.035±0.063 logMAR (p=0.012) at final follow-up. Central macular thickness at baseline was 349.2±53.2 μm, which was changed to 250.7±28.8 μm (p=0.009) at the 3month follow-up and 261.2±38.31 μm (p=0.009) at final follow-up. Conclusions Subthreshold micropulse yellow laser photocoagulation showed short-term efficacy in treating chronic CSC without retinal damage. However, prospective, randomized, and comparative large-scale studies are needed to evaluate the efficacy and safety of this treatment.
Keywords Central serous chorioretinopathy . Subthreshold micropulse yellow laser photocoagulation J. Y. Kim : H. S. Park : S. Y. Kim (*) Nune Eye Hospital, 18-21F LIG Bldg, 2397, Dalgubeol-daero, Suseong-gu, Daegu, Republic of Korea e-mail: [email protected]
Introduction Central serous chorioretinopathy (CSC) was first described in 1866 by Albrecht von Graefe, who named it ‘relapsing central luetic retinitis’ [1]. In 1967, Gass suitably renamed the condition as CSC [2]. CSC is a chorioretinal disorder, incompletely understood, that has systemic associations, multifactorial etiology, and complex pathogenesis. It typically affects young to middle-aged men, and is characterized by serous detachment of the neurosensory retina, which is usually located at the posterior pole [3]. The natural course of this disease is relatively benign. However, some patients with frequent recurrences or chronic neurosensory retinal detachment may develop retinal pigment epithelium (RPE) atrophy and neurosensory retinal atrophic changes, resulting in permanent loss of visual function, including visual acuity, color vision, and contrast sensitivity [4–7]. In these chronic or recurrent cases, treatment options include focal laser treatment, photodynamic therapy (PDT), and intravitreal anti-vascular endothelial growth factor (VEGF) medications [8]. Focal laser photocoagulation is commonly used to expedite the absorption of subretinal fluid (SRF) in acute and chronic CSC. Some reports have indicated that laser treatment was associated with a decreased rate of recurrences. However, this remains controversial [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 (CNV), and potential new sites of leakage [8]. Verteporfin PDT has shown promise by not only promoting resolution of acute CSC, but also preventing recurrences. Studies in chronic disease have yielded favorable results as well [10–13]. However, PDT has side-effects, such as choroidal ischemia, RPE atrophy, iatrogenic CNV, and RPE rip [14–17]. Intravitreal anti-VEGF injections are considered adjuvant treatments for CSC. Many studies have demonstrated
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anatomic and functional improvement following intravitreal anti-VEGF injection [18–22]. But Bae and colleagues reported the overall superiority of low-fluence PDT compared to intravitreal ranibizumab injection in the treatment of chronic CSC [23, 24], Currently, anti-VEGF agents are not considered as first-line treatment of chronic CSC.[9] Advances in laser technology have led to the development of selective photocoagulation for RPE via the subthreshold micropulse (STMP) laser photocoagulation method. 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 [25]. Application of STMP diode laser in the setting of CSC has been previously described [8, 25–29]. A new semiconductor laser device now provides solid-state 577-nm yellow laser light. Because this subthreshold micropulse yellow laser (SMYL) system was recently commercialized, no clinical studies of this system for chronic CSC have been reported to date. This 577-nm yellow laser system (Supra 577Y Laser System; Quantel Medical, ClermontFerrand, France) has been used for retinal treatment in our clinic since April 2011. The purpose of this retrospective study was to evaluate the short-term effect of subthreshold micropulse yellow laser photocoagulation (SMYLP) on eyes with chronic CSC using this laser system.
Fig. 1 Fluorescein angiography of a 31-year-old male patient (patient no. 7) and a 47-year-old male patient (patient no. 8). On fluorescein angiography, the no. 7 case has a definite leaking point near the fovea (a: early phase, b: late phase), and in the no. 8 case, a diffuse leaking pattern was observed (c: early phase, d: late phase)
Materials and methods We performed a retrospective case series study of ten eyes from ten patients who underwent SMYLP for chronic or chronic recurrent CSC at Nune Eye Hospital (Daegu, Korea) from April 2012 to June 2014. This study adhered to the ethical standards in the Declaration of Helsinki. Inclusion criteria were: symptomatic CSC of 6 months or greater, recurrent CSC patients with a history of chronic CSC, and patients who had received SMYLP for CSC treatment. Exclusion criteria were: (1)patients who had a history of another macular disease history such as age-related macular degeneration, retinal vascular occlusion, diabetic retinopathy, or epiretinal membrane, (2) patients who had received antiVEGF treatment (ranibizumab or bevacizumab), conventional thermal laser, intraocular surgery, or PDT in the past 3 months before and during SMYLP treatment, or (3) patients who were not followed up over 3 months after the start of SMYLP treatment. All patients received comprehensive ophthalmic examinations, including anterior segment examination and dilated biomicroscopic fundus examination. Best-corrected visual acuity (BCVA) was determined using a Snellen visual acuity (VA) chart. BCVA was converted to logarithm of the minimum angle of resolution (logMAR) units for statistical
1
1
40/M 42/M 47/M 44/M 40/M 44/M 31/M 47/M 52/M 52/M 1 2 3 4 5 6 7 8 9 10
F/U follow-up, BCVA best-corrected visual acuity, logMAR logarithm of the minimum angle of resolution, CMT central macular thickness, M male; NDL no definite leaking point
1,224 1,008 513 306 900 3,708 198 3,960 2,637 1,971 256 273 244 272 266 199 219 300 334 249 243 274 244 272 263 199 218 300 245 249 328 315 350 279 326 380 395 285 385 449 0 0.15 0 0 0 0 0 0.05 0.15 0 0 0.3 0 0 0 0.05 0.05 0.05 0.1 0 0.15 0.3 0.4 0.1 0.15 0.7 0.1 0 0.2 0 2 1 1 1 1 2 1 4 4 2 5 6 3 10 11 18 11 3 10 3
Age/sex
Table 1
We performed a retrospective study of ten eyes from ten patients with chronic or chronic recurrent CSC. All patients were male with mean age at diagnosis of 43.9±6.24 years (range, 31–52 years). There were three patients who had received previous anti-VEGF treatments before SMYLP treatment. Only one case had received a previous conventional focal
Data summary
Results
Patient (eye)
Distance between leaking point and foveal center, μm
Post treatment F/U period, months
No. initial treatment session
No. retreatment session for recurrent case
Initial BCVA (logMAR)
BCVA at 3 months (logMAR)
BCVA at the final F/U (logMAR)
Initial CMT, μm
3 months CMT, μm
Final CMT, μm
analysis. Color fundus photography and fluorescein angiography (Spectralis HRA; Heidelberg Engineering; Heidelberg, Germany) were performed before SMYLP treatment. Spectral-domain optical coherence tomography (SD-OCT) (Spectralis OCT; Heidelberg Engineering) was performed before SMYLP as well as during every follow-up visit. All treatments were provided by a single practitioner (H.S. Park) with the 577-nm yellow laser system (Supra 577Y Laser System). Laser application was performed with an AreaCentralis lens (Volk Optical, Mentor, OH, USA). Micropulse laser power used in SMYLP was derived for each eye from a test burn. Subthreshold treatment was performed in the micropulse mode, using a 100-μm spot diameter and a 20ms duration with 15 % duty cycle. An energy level below the threshold was used for a test burn. A single threshold burn was made in micropulse mode, and then the laser power reduced 50 % from the power of a single threshold burn, so that no visible retinal changes were made. In most cases, laser was applied in the energy level from 250~350 mW. Laser shots were delivered together in a 3×3 pattern mode (1.0 widths) over the entire area of CSC, including the leaking point on fluorescein angiogram and the foveal center. We also applied micropulse yellow laser on the normal retina around the borderline area of serous retinal detachment. At follow-up, BCVA assessment, macular OCT, and treatment responses were recorded. If the SRF was not completely resolved in a month after laser application, SMYLP was repeated until the SRF was completely resolved with monthly treatment pattern. Recurred CSC patients received SMYLP retreatment. We mainly observed the mean BCVA change and change of central macular thickness (CMT) over time as assessed by image-tracked Heidelberg Spectralis OCT volume scans from baseline to 3 months after SMYLP treatment and final followup. We also checked the mean choroidal thickness change assessed by enhanced depth imaging OCT (EDI-OCT) technique until final follow-up. The number of recurring CSC cases after SMYLP, and the incidence of adverse events were counted. Data were presented as mean±standard deviation. The post-treatment values were compared with the baseline values using the Wilcoxon signed-rank test. Statistical analyses were performed using SPSS ver. 18.0 (SPSS Inc., Chicago, IL, USA). Statistical significance was considered when p-value was less than 0.05.
397 375 790–1,421 NDL 2,990 NDL 1,606 NDL NDL 1,316
No. total laser spots
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laser treatment. There was no case that received previous PDT. The mean pre-SMYLP treatment follow-up period was 14.5± 8.3 months (range, 6–24 months). On fluorescein angiography, four cases have a diffuse leaking pattern, and in six cases, definite leaking points were observed. The mean distance between the leaking point and foveal center is 1,271 μm (Fig. 1). Specifics of data are summarized in Table 1. The findings for a 31-year-old man who underwent successful SMYLP are presented in Fig. 2. The mean post-SMYLP treatment follow-up period was 8 ±4.88 months (range, 3–18 months). The mean number of treatment sessions, including initial treatment and retreatment, was 2.1±1.45 (range, 1–5). The mean number of total laser shots was 1642.5±1374.84 (range, 198–3,960). There were two patients who had recurrent CSC. One recurrent case (patient no. 6) occurred at 6 months after the initial SMYLP treatment. Another case (patient no. 9) occurred at 10 months after the initial SMYLP treatment (Fig. 3). These two patients received SMYLP retreatment. One of these patients (patient no. 6) responded to retreatment, but the other patient (patient
no. 9) did not visit the next follow-up after retreatment. One case (patient no. 8) had persistent SRF for 3 months despite a total of four treatment sessions. Mean BCVA before treatment was 0.21±0.21 (range, 0–0.7 logMAR). Mean BCVA at 3 months after treatment was 0.055 ±0.093 (range, 0–0.3 logMAR). Mean BCVA at final followup was 0.035±0.063 (range, 0–0.15 logMAR). The BCVA was improved with statistical significance at 3 months (p=0.020) and at final follow-up (p=0.012) after the initial SMYLP treatment. Mean CMT before treatment was 349.2±53.22 μm (range, 279–449 μm). Mean CMT at 3 months after treatment was 250.7±28.79 μm (range, 199–300 μm). Mean CMT at final follow-up was 261.2±38.31 μm (range. 199–334 μm). CMT was decreased with statistical significance at 3 months (p=0.009) and at final follow-up (p=0.009) after the initial SMYLP treatment. Mean choroidal thickness before treatment was 398.7±87.02 μm (range, 276–525 μm). Mean choroidal thickness at 3 months after treatment was 400.5±93.52 μm (range, 274–525.7 μm). Mean choroidal thickness at final follow up was 399.8±99.35 μm (range, 260–529.7 μm). The
Fig. 2 Fundus photo, near infra-red images and spectral-domain optical coherence tomography images of the macula of a 31-year-old male patient (patient no. 7). Right eye before subthreshold micropulse yellow
laser photocoagulation (SMYLP) treatment (a, b), 3 months after SMYL P treatment (c, d), and 11 months after SMYLP treatment (e, f)
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choroidal thickness did not change with statistical significance at 3 months (p=0.878) or at final follow-up (p=0.859) after the initial SMYLP treatment. When before and after fundus color photographs, SD-OCT, and near infra-red images were compared, no laser scar was detected in color fundus photographs, SD-OCT, or near infrared images.
Discussion CSC can be classified into acute and chronic forms [3]. The natural course of acute CSC is believed to be very good, with primary cases being resolved spontaneously in 3 to 4 months [30, 31]. However, some patients are known to be associated with recurrent or persistent detachments. In these cases, the disorder is referred to as chronic CSC, which is arbitrarily defined as detachments lasting 6 months or longer [32]. Chronic CSC can result in diffuse RPE damage. These patients have long-standing SRF that cannot be reabsorbed efficiently because of choroidal disease and extensive dysfunction and loss of RPE. The presence of chronic SRF can lead to photoreceptor death, which can result in permanent visual loss. Furthermore, chronic CSC is likely to be complicated by CNV that can cause severe visual loss [9]. Not all patients with CSC have the chronic form. The reasons for Fig. 3 Fundus photo, near infrared images and spectral-domain optical coherence tomography images of the macula of a 52year-old male patient (patient no. 9). Right eye before subthreshold micropulse yellow laser photocoagulation (SMYLP) treatment (a, b), 3 months after SMYLP treatment (c, d), and 10 months after SMYLP treatment (e, f). He received SMYLP retreatment at 10 months after the initial treatment, but he didn’t visit at the next follow-up
varied courses are not well understood. The pathophysiology of CSC remains poorly understood despite advances in imaging techniques and many studies on this disease. Multiple etiologies and mechanisms that ultimately lead to choroidal circulation abnormalities have been suggested [33]. Hyperdynamic choroidal circulation and choroidal vascular hyperpermeability are the main features shared by patients with CSC [34]. Thermal laser photocoagulation for treating of CSC was based on the observation that a conventional laser photocoagulation of a fluorescein-detectable pigment epithelial leak may accelerate resolution of the associated neurosensory detachment [3, 9, 30, 35]. However, if the area of leakage is subfoveal or juxtafoveal, photocoagulation may induce secondary CNV and/or of damage to foveal photoreceptors. Several studies showed that no difference in final VA or in recurrence rate between eyes treated with argon laser photocoagulation and untreated eyes in long-term followed-up CSC patients [36]. Micropulse diode laser treatment targets a series of ultrashort 810 nm laser pulses at the tissue of interest. These repetitive bursts allow lower total energy use and help minimize damage to surrounding tissues from harmful thermal effects [37]. Retina-sparing photocoagulation is of particular interest in CSC. Bandello and colleagues first reported micropulse diode laser as a treatment option for CSC to avoid risks of
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harmful thermal events in treating symptomatic chronic CSC [38]. Subsequently, Chen and colleagues reported a series of 26 eyes of 25 patients in which 14 of 15 eyes with focal leaks had SRF resorption; only five of 11 eyes with diffuse leakage cleared all fluid. They concluded that STMP laser was effective in the treatment of CSC with point source leakage [26]. Ricci and colleagues have reported a series of seven eyes with persistent SRF, all of which were fluid-free at 1 year post STMP treatment [12, 29]. Recently, Malik and colleagues reported a retrospective case series study in which eight of 11 eyes after a single treatment session had decreased maximum macular thickness [8]. In short, 810-nm diode STMP laser is a potential treatment option as a safe treatment modality for patients with chronic CSC. Recently, a new 577-nm SMYLP device (Supra 577Y Laser System; Quantel Medical, Clermont-Ferrand, France) was introduced. Theoretically, the 577-nm yellow laser light provides peak absorption of oxyhemoglobin, excellent lesion visibility, low intraocular light scattering and pain, and negligible xanthophyll absorption [39, 40]. This leads to energy being concentrated in a smaller volume, which in turn allows for a reduction in power and shortened pulse duration. Additionally, the 577-nm yellow laser wavelength has the advantage of being better absorbed by melanin than the 810-nm laser wavelength, a characteristic that is theoretically suited to micropulse technique aimed at RPE cells. To our knowledge, this study is the first study on the efficacy and safety of 577-nm SMYLP treatment for chronic CSC. In this study, 577-nm SMYLP for chronic CSC showed good short-term clinical effect for improving BCVA and CMT. The second finding of our study was that SMYLP did not cause any chorioretinal damage in the human eye despite repeated micropulse laser treatments (shown by color fundus photographs, near infra-red photographs, and SD-OCT images, although these images can overlook microstructural chorioretinal damage). However, two cases had recurrent CSC and one case had persistent SRF. We found no significant choroidal thickness change assessed by EDI-OCT technique. These findings suggest that SMYLP for chronic CSC is effective and safe. However, this treatment modality may not prevent the recurrence of CSC perfectly. Maybe SMYLP only affects the RPE dysfunction without influencing the hyperdynamic choroidal circulation and choroidal hyper-permeability that have been thought the primary cause of CSC. Further study is needed to determine how SMYLP works in CSC. This study has several limitations. It was a small-sized retrospective case series study with an irregular follow-up period without a control group. Furthermore, we did not have a detailed standard treatment protocol and procedure guideline, including laser power setting, precise indications of retreatment, follow-up plan, and retreatment plan. Therefore, our data should be interpreted with caution. However, this study provide information for further study.
In conclusion, we suggest SMYLP may be one of the treatment options for chronic CSC. SMYLP may be effective as conventional laser treatment but safer than conventional laser photocoagulation and PDT. Prospective, randomized, largescale, long-term follow-up studies will be required to further evaluate the therapeutic efficacy and safety of SMYLP treatment for chronic CSC. Conflict of interest No potential conflict of interest relevant to this article was reported.
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