FP85 : Role of 532nm subthreshold micropulse laser in nonresolving CSCR with subfoveal leaks.

Dr. Vikas Ambiya, Dr. ASHOK KUMAR, Mr. Gaurav Kapoor

Abstract

Purpose:

Role of 532nm subthreshold micropulse laser (STMPL) in non-resolving central  serous chorioretinopathy (CSC) with subfoveal leak.

Methods:

Prospective study on 23 eyes of 21 patients. Inclusion criteria: vision loss ≥3 months; focal subfoveal leak on fluorescein angiography. Exclusion criteria: prior treatment for CSC; chronic CSC. All eyes were treated with 532nm STMPL (5% duty cycle). Visual acuity score (VAS), contrast sensitivity (CS), autofluorescence, spectral domain optical coherence tomography, fundus fluorescein angiography were assessed at baseline, 1, 3, 6 months.

Results:

Average VAS (letters) improved from 78.08±8.51 (baseline) to 83.35±8.48 (1 month, P<0.01), 86.91±20.16 (3 months, P<0.01), 92.43±9.44 (6 months, P<0.01). CS improved from 0.75±0.30 to 1.30±0.37 (P<0.01) at 6 months. 2 eyes needed rescue STMPL at 3 months and the same eyes needed photodynamic therapy at 6 months.

Conclusion:

532 nm STMPL is safe and effective in nonresolving CSC with subfoveal leaks.

Key words: Central serous chorioretinopathy; subthreshold micropulse laser; subfoveal leak 

Introduction

Central serous chorioretinopathy (CSC) is a disease that is characterized by serous macular detachment with or without retinal pigment epithelium (RPE) detachment. It is an idiopathic disease that is more prevalent in middle-aged men. Stress and corticosteroid intake are well-known precipitating factors. Most of the cases resolve spontaneously within 3 or 4 months with good visual prognosis. Considerable visual impairment occurs if the subretinal fluid persists for more than 3 months.

Conventional laser cannot be applied in subfoveal and juxtafoveal leaks on FFA in cases of CSC, as it carries the risk of central or paracentral scotomas, accidental foveal burn, and choroidal neovascularization. PDT is a viable option in these cases, but it carries its own inherent risk of RPE atrophy, choroidal neovascularization, and choriocapillaris ischemia and is an expensive procedure. [1]

Micropulse is a laser modality that divides a continuous stream of laser into a number of short bursts separated by pauses (off time). According to the selected duty cycle, the laser stays on only 5%–15% of the time, thus generating less heat and preventing build-up of thermal heat with subsequent less damage to the retina than continuous-wave photocoagulation. STMP laser emission without a visible burn endpoint appears to reduce the risk of structural and functional retinal laser damage, allowing treatment of foveal lesions without post-laser scotomas.

STMP laser has been successfully used for diabetic macular edema [2] and seems to be comparable to conventional argon laser. In 2003, Bandello et al were the first to propose subthreshold diode micropulse photocoagulation for the treatment of CSC, showing positive results in a series of five cases.[3] Ricci et al showed that SDM can provide therapeutic benefits similar to those obtainable with standard-threshold continuous-wave laser photocoagulation, but without causing discernible chorioretinal lesions, allowing almost confluent therapy and retreatment of persistent or new leaking points.[4] Micropulse laser causes stimulation of a biological response that restores the proper pump function of RPE cells, resulting in enhanced and rapid absorption of subretinal fluid.

All studies on role of micropulse laser in CSC have been conducted using 810 nm or 577 nm wavelength.[3-6] There are no studies reporting the role of 532 STMP laser in treating CSC. This project aims to prove the efficacy of the said laser in treating non-resolving CSC with subfoveal leaks.

Methods

This prospective interventional study was carried out at a tertiary eye institute to evaluate the role of 532 nm STMP laser in treating cases of persistent CSC with focal subfoveal leaks on FFA. This study was conducted after obtaining approval from the institutional ethical committee, and in accordance with the tenets of the Declaration of Helsinki. An informed consent was obtained from each study subject.

The inclusion criteria were: 1) age ≥  18 years; 2) diminution of vision for a duration of minimum 3 months due to persistent CSC; 3) subfoveal fluid seen on spectral domain optical coherence tomography (SD-OCT) imaging; 3) focal subfoveal leak on fundus fluorescein angiography (FFA).

The exclusion criteria were: 1) chronic CSC characterized by RPE atrophy, diffuse leak on FFA; 2) history of treatment for CSC in the past; 3) multiple leaks on FFA; 4) any other vitreoretinal disorder currently or in the past; 5) any intraocular procedure in the past 6 months; 6) currently on systemic or topical steroid therapy; 7) presence of opaque media likely to affect quality of imaging; 12) spherical equivalent ≥ ±6D.

A detailed systemic and ocular history (onset of symptoms, present and previous treatment), the demography (age, gender), laterality, and systemic comorbidities were recorded.

A comprehensive ocular examination was done which included an assessment of the best-corrected distance visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) chart;  contrast sensitivity measured uniocularly at 1 meter using the Pelli-Robson chart and expressed as logarithmic CS; spherical equivalent of refractive status of the eye; slit lamp biomicroscopy with a noncontact lens; and indirect ophthalmoscopy. Color fundus photographs of the optic disc, macula, and temporal retina (30°) were captured with a mydriatic camera (Zeiss FF450, Carl Zeiss Meditec, Jena, Germany).

FFA

FFA was performed using fluorescein sodium 20% and imaging on a mydriatic camera (Zeiss FF450, Carl Zeiss Meditec, Jena, Germany) at baseline, and at 3 and 6 months from baseline. A subfoveal leak on FFA was defined as a focal leak within 500 μm from the center of fovea.

SD-OCT

All eyes underwent SD-OCT imaging using spectral domain OCT (Carl Zeiss Meditec, Inc.,5160 Hacienda Drive, Dublin, CA 94568 USA). The scanning protocols included HD 21 line raster and macular cube 512×128 scan. The central subfield retinal thickness (CMT) was determined automatically and analysed by the OCT software. The subfoveal height of neurosensory detachment was measured with callipers on the line scan passing through the fovea. The OCT imaging was done at baseline and subsequently at each visit of follow-up.

Autofluorescence

Fundus autofluorescence imaging (50 degrees) was done usingmydriatic camera (Zeiss FF450, Carl Zeiss Meditec, Jena, Germany)to assess any signs of subclinical laser burns at the site of application of the micropulse laser.

Subthreshold microsecond laser

The point of focal leakage in the subfoveal area was noted on FFA.  All eyes were be treated with the 532-nm subthreshold micropulse laser using slit lamp delivery. Initially, the power of 532 nm laser was titrated to just produce a mild retinal whitening outside the vascular arcade, using 5% duty cycle, “test” spot size of 100 μm and 200 ms exposure time. Following this, a 5×5 grid of confluent spots was aplied over the area of focal leak, using the same settings with just 5% of the threshold power. Area centralis contact lens was used to deliver the laser.

Rescue laser

Rescue microsecond laser, with the same settings as in primary laser treatment, was applied at the site of leakage if there was no change or if there was an increase in NSD on SD-OCT at 3 months from baseline.

Outcome measures

Primary outcome measures included change in BCVA and low-contrast visual acuity at 6 months follow-up compared to baseline. Secondary outcome measures included resolution of NSD and the incidence of adverse effects of the laser including subjective reports of scotoma, evidence of retinal tissue damage on FFA, AF, OCT or clinical examination.

Statistical analysis

The BCVA and low-contrast visual BCVA were calculated as ETDRS visual acuity score in the form of number of letters. The changes from baseline in BCVA, height of NSD, AND CMTat 1, 3, and 6 months were analyzed with Wilcoxon signed-rank test. P-value of<0.05 was regarded as statistically significant.

Results

We studied 23 eyes of 21 patients with a mean age of 37.09±3.27 years. All patients were male. All study eyes were treatment-naïve eyes with persistent CSC of a duration of more than three months, with a single focal subfoveal leak on FFA. The average duration of symptoms was 4.48±1.86 months. The baseline features of the study eyes are mentioned in Table 1. The clinical and imaging characteristics of the individual cases at baseline and at the end of follow-up of six months are summarized in Table 2.

All ten eyes were treated with a sitting of STMP laser at baseline. The laser power used in our study ranged from 35 to 60mW. There was an improvement in the BCVA from 78.08±8.51 ETDRS letters at baseline to 83.35±8.48 (P=0.01) letters at 1 month, 86.91±20.16(P<0.01) letters at 3 months and 92.43±9.44 (P<0.01) letters at 6 months, and the change was statistically significant at each visit when compared to baseline. Similarly, the contrast sensitivity significantly improved from 0.75±0.30 at baseline to 1.30±0.37 (P<0.01) at 6 months.

At 1 month, there was total resolution of SRF in nine (39.13% of 23) eyes and reduction in the NSD height in nine (64.29% of 14) of the remaining 14 study eyes.

At 3 months, 12 eyes (52.17% of 23) had no SRF. Of the remaining nine eyes, two eyes did not show a progressive decrease in the height of NSD and were therefore given rescue laser. Both of these eyes did not show complete resolution of SRF even at 6 months and were subsequently treated with PDT and are presently under follow-up.

At 6 months, 16 (69.57% of 23) eyes showed complete resolution of SRF. Two of the remaining seven eyes showed an increase in the height of NSD in spite of rescue laser at 3 months from baseline and were therefore advised PDT at 6 months. Another two eyes showed a very gradual decrease in the height of NSD and were treated with repeat STMP laser.

Overall, the NSD height was significantly decreased from 260.96 ± 174.14μm at baseline to 140.70 ± 134.90 μm (P<0.01) at 1 month, 68.78 ± 89.79 μm (P<0.01) at 3 months, and 47.96 ± 87.26μm (P<0.01) at 6 months. Similarly the CMT was significantly reduced from 416.43 ± 171.91 μm at baseline to 296.65 ± 117.48 μm (P<0.01) at 1 month, 240.74 ± 84.61 μm (P<0.01) at 3 months, and 227.57 ± 69.10 μm (P<0.03) at 6 months.

Safety

No laser spots were visualized on any post-laser visits by biomicroscopy, SD-OCT, or on fundus autofluorescence. None of the patients had any procedure-related complications.

Discussion

There is ample literature on the use of subthreshold diode laser micropulse photocoagulation in the management of CSC.[4-6] There is a recent study on the use of 577 nm microsecond laser in treating subfoveal leaks in CSC.[7]But there is no published literature on the use of 532 nm STMP laser in eyes having subfoveal leaks on FFA.

We treated eyes that had SRF for a duration of 3 months or more. We found total resolution of SRF in 39.13% eyes at the end of one month and in 69.57% eyes within 6 months after treatment. It implies that 532nm STMP laser was effective in treating these eyes, and the effect was not by chance. Two of the 23 eyes, in which SRF did not resolve at all or increased with time, were treated with PDT and are under follow-up.

Rescue laser may be required in eyes that do not respond within 3 months after initial laser. But these eyes generally are less responsive and might need an alternate therapy later.

STMP laser definitely has an advantage over PDT in terms of cost effectiveness and is a good option especially for patients who cannot afford PDT. Another advantage is the safety profile of the subthreshold micropulse mode of laser.

One of the major limitations of our study is a small sample size which can be explained by the rarity of occurrence of subfoveal leak as a cause of persistent CSC. Secondly we did not have a study arm undergoing simply observation or a different intervention to compare with in order to ascertain the effective role of the 532 nm STMP laser.

Conclusion

Subthreshold micropulse laser is a safe and effective treatment for persistent CSC with subfoveal leak on FFA. However there may be a need for repeat micropulse laser in cases that do not respond or show recurrence. We recommend prospective studies on a larger sample size and longer follow-up to ascertain the long term role of this modality of treatment.

Disclosure

The authors report no conflicts of interest in this work. 

References

1. Colucciello M. Choroidal neovascularization complicating photodynamic therapy for central serous retinopathy. Retina. 2006;26(2):239–242.
2. Vujosevic S, Martini F, Convento E, et al. Subthreshold laser therapy for diabetic macular edema: metabolic and safety issues. Curr Med Chem. 2013;20(26):3267–3271.
3. Bandello F, Lanzetta P, Furlan F, Polito A. Non visible subthreshold micropulse diode laser treatment of idiopathic central serous chorioretinopathy. A pilot study. Invest Ophthalmol Vis Sci. 2003;44:4858.
4. Ricci F, Missiroli F, Regine F, Grossi M, Dorin G. Indocyanine green enhanced subthreshold diode-laser micropulse photocoagulation treat­ment of chronic central serous chorioretinopathy. Graefes Arch ClinExp Ophthalmol. 2009;247(5):597–607.
5. Lanzetta P, Furlan F, Morgante L, Veritti D, Bandello F. Nonvisible subthreshold micropulse diode laser (810 nm) treatment of central serous chorioretinopathy. A pilot study. Eur J Ophthalmol. 2008;18(6):934–940.
6. Chen SN, Hwang JF, Tseng LF, Lin CJ. Subthreshold diode micropulse photocoagulation for the treatment of chronic central serous chori­oretinopathy with juxtafoveal leakage. Ophthalmology. 2008;115(12):2229–2234.
7. Ambiya V, Goud A, Mathai A, Rani PK, Chhablani J. Microsecond yellow laser for subfoveal leaks in central serous chorioretinopathy. Clinical Ophthalmology. 2016;10:1513–1519

Table 1 Baseline parameters and changes in follow-up after microsecond laser therapy

Parameter	Baseline	1 month	3 months	6 months
Average BCVA (ETDRS letter score ± SD)	78.08±8.51	83.35±8.48 (P=0.01)*	86.91±20.16(P<0.01)*	92.43±9.44 (P<0.01)*
Contrast sensitivity	0.75±0.30	–	–	1.30±0.37 (P<0.01)
Average CMT (μm) ± SD	416.43±171.91	296.65±117.48 (P<0.01)*	240.74±84.61(P<0.01)*	227.57±69.10 (P<0.01)*
Average NSD height (μm) ± SD	260.96±174.14	140.70±134.90 (P<0.01)*	68.78±89.79 (P<0.01)*	47.96±87.26 (P<0.01)*

 

Notes: *Statistically significant when compared to baseline. All P-values are with respect to baseline.

Abbreviations: BCVA, best-corrected visual acuity; CMT, central macular thickness; ETDRS, Early Treatment Diabetic Retinopathy Study; logMAR, logarithm of the minimum angle of resolution; NSD, neurosensory detachment; SD, standard deviation.

Table 2. Features of individual study eyes at baseline and at six months.

Case No.	Age/Gender	Eye	Disease Duration (months)	Baseline			Rescue laser at 3 months	6 months			Rescue laser/ PDT advised at last visit
				BCVA (ETDRS letter score)	Low contrast BCVA (Letter  score)	NSD height (µm)		BCVA (ETDRS letter score)	Low contrast BCVA(Letter score)	NSD height (µm)
1	33/M	OD	8	76	0.80	384	–	70	0.65	166	Laser
2	34/M	OS	5	70	0.65	365	–	85	1.10	0	–
3	44/M	OD	3	85	0.65	139	–	100	1.40	0	–
4	35/M	OS	3	61	0.35	121	–	100	1.55	0	–
5	38/M	OD	4	76	0.5	459	–	100	1.70	93	–
6	37/M	OS	3	85	0.80	73	–	100	1.70	0	–
7	33/M	OS	3	70	0.35	744	–	85	0.95	259	Laser
8	33/M	OD	8	76	0.50	286	–	85	1.10	0	–
9	35/M	OD	6	70	0.35	239	–	85	1.10	0	–
10	42/M	OS	6	76	0.65	265	–	91	1.25	54	–
11	34/M	OS	3	70	0.65	624	–	100	1.55	0	–
12	40/M	OD	4	76	0.50	239	–	100	1.70	0	–
13	40/M	OS	3	85	1.10	157	–	100	1.55	0	–
14	41/M	OD	3	85	0.80	419	–	100	1.55	0	–
15	40/M	OS	3	61	0.35	134	–	100	1.70	0	–
16	40/M	OS	6	85	0.95	86	Yes	76	0.50	172	PDT
17	41/M	OS	5	76	0.95	134	–	91	0.80	79	–
18	35/M	OS	4	85	1.10	259	–	100	1.70	0	–
19	35/M	OS	3	91	1.10	112	–	100	1.70	0	–
20	36/M	OD	3	85	1.25	192	–	91	0.95	0	–
21	36/M	OS	4	91	1.10	93	–	100	1.55	0	–
22	34/M	OS	9	85	1.25	166	Yes	76.00	0.95	280	PDT
23	37/M	OD	4	76	0.65	312		91.00	1.25	0	–

BCVA, best corrected visual acuity; NSD, neurosensory detachment; ETDRS, early treatment diabetic retinopathy study; PDT, photodynamic therapy.