Change of Regional Choroid Thickness After Reduced-Fluence Photodynamic Therapy for Chronic Central Serous Chorioretinopathy




Purpose


To evaluate macular choroidal thickness after reduced-fluence photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSC).


Design


Prospective, consecutive, interventional case series.


Methods


Twenty-two eyes with chronic CSC were treated with reduced-fluence PDT. Macular choroidal thickness was examined using spectral-domain optical coherence tomography with a 3-dimensinonal radial scan protocol in the choroidal mode before and 1, 3, and 6 months after the treatment. The mean choroidal thickness in the Early Treatment Diabetic Retinopathy Study grid (center, inner circle, and outer circle) was compared between before and after therapy, as well as between treated eyes and 54 volunteer normal eyes.


Results


Chronic CSC eyes showed significantly thicker choroids in the macular area compared with normal controls ( P < .0001). After the single treatment session, subretinal fluid resolved completely in all eyes, and there were no recurrences during the study period. Choroidal thickness within the center area and inner circle showed a significant reduction at all time points after treatment ( P < .05). The choroidal thickness in the outer circle showed a statistically significant reduction at 1 and 3 months but not at 6 months. After treatment, the choroidal thickness reduced to the normal values at the center and inner circle, but was still significantly thicker in the outer circle ( P < .01).


Conclusion


Chronic CSC eyes showed significantly thicker choroids in the macular area. After reduced-fluence PDT, macular choroidal thickness became thinner within 6 months of treatment.


It was previously thought that a breakdown of the outer blood-retinal barrier leads to leakage from the retinal pigment epithelium in central serous chorioretinopathy (CSC). Recent studies using indocyanine green angiography have revealed delayed choroidal infusion, choroidal venous dilation, and choroidal vascular hyperpermeability in eyes with CSC. It is now generally thought that the choroid is the primary site involved in CSC pathology. In addition, enhanced-depth imaging optical coherence tomography (OCT) showed that eyes with CSC have thicker choroids at the fovea than contralateral unaffected eyes or healthy normal eyes. A comparison of choroidal thickness between regions with and without choroidal vascular hyperpermeability showed greater choroidal thickness in the region with choroidal vascular hyperpermeability. The choroidal thickening diffuses, extending over the macula, rather than just being localized subfoveally.


Photodynamic therapy (PDT) with verteporfin resolves leakage and subsequently resolves subretinal fluid in chronic CSC. A possible mechanism of action of PDT in CSC involves damage to the choriocapillaris leading to decreased choroidal vascular hyperpermeability and a subsequent reduction in leakage from the retinal pigmented epithelium. Most reports on post-PDT changes in choroidal thickness in CSC eyes, however, have focused on the subfoveal choroidal thickness; there have been few reports focusing on changes in perifoveal choroidal thickness. Moreover, no reports have compared whole macular choroidal thickness measurements between the reduced-fluence PDT-treated eyes and normal control eyes.


In the present study, we scanned the whole macular area of patients with CSC by high-resolution spectral-domain OCT using a 3-dimensional radial scan protocol. The choroidal thickness maps were used to study changes in choroidal thickness before and after reduced-fluence PDT and to compare reduced-fluence PDT–treated eyes and normal control eyes.


Methods


This study was approved by the Ethics Committee at Kagawa University Faculty of Medicine and conducted in accordance with the tenets of the Declaration of Helsinki. The current prospective, interventional study included consecutive patients presenting with unilateral treatment-naïve active chronic CSC between July 2, 2012 and March 29, 2013 at the Kagawa University Hospital. Inclusion criteria were as follows: age >20 years and diagnosis of active CSC for at least 6 months, defined as the presence of subretinal fluid involving the macula. The leakage points were unclear with idiopathic diffuse leaks from the damaged retinal pigment epithelium or involved the fovea in fluorescein angiography.


The control group consisted of 54 normal eyes (28 eyes in 21 men and 26 eyes in 16 women; mean age, 54.1 ± 16.8 years). No significant differences existed between the control and CSC patient groups with respect to age, sex, and refractivity. The criteria for exclusion from the study included multiple retinal pigment epitheliopathy, ocular hypertension >21 mm Hg, myopia <−6.0 diopters (D), and a history of intraocular surgery.


The macular area was examined using the RS-3000 Advance system (NIDEK, Gamagori, Japan) in the choroidal mode ( Figure 1 ). The radial scan consisted of 9-mm line scans in 6 radial directions. The super-fine choroidal mode provides high-resolution images of the choroid. The lines of the retinal pigment epithelium–Bruch membrane complex and the chorioscleral border were segmented automatically by the equipped software with manual correction, if necessary. A choroidal thickness map on the macular area was made and the average choroidal thickness at each Early Treatment Diabetic Retinopathy Study (ETDRS) grid was calculated by the equipped software. Choroidal thickness measurements were taken before and 1, 3, and 6 months after reduced-fluence PDT. The ETDRS map was fused to 3 areas ( Figure 2 ): center, the central circle within a 1-mm diameter; inner circle, a donut-shaped ring with an inner diameter of 1 mm and an outer diameter of 3 mm; and outer circle, a donut-shaped ring with an inner diameter of 3 mm and an outer diameter of 6 mm.




Figure 1


Choroidal thickness map with a grid from the Early Treatment Diabetic Retinopathy Study. (Top left) The macular area was examined with the RS-3000 Advance system in the choroidal mode. Radial scans consisting of 9-mm line scans in 6 radial directions were obtained. (Top right) The lines of the retinal pigment epithelium–Bruch membrane complex (pink) and the chorioscleral border (blue) were segmented automatically by the equipped software. (Bottom left) Choroidal thickness maps of the macular area. (Bottom right) Mean choroidal thickness of the Early Treatment Diabetic Retinopathy Study grid.



Figure 2


Definition of the 3 areas for the comparison of the regional choroidal thickness. The Early Treatment Diabetic Retinopathy Study grid was fused into 3 areas, shown as a lattice pattern: (Left) center, the central circle within a 1-mm diameter; (Middle) inner circle, a donut-shaped ring with an inner diameter of 1 mm and an outer diameter of 3 mm; and (Right) outer circle, a donut-shaped ring with an inner diameter of 3 mm and an outer diameter of 6 mm.


All eyes with chronic CSC underwent reduced-fluence PDT. The maximum diameter of PDT irradiation covered the area of choroidal vascular hyperpermeability in the indocyanine green angiography image and the area with fluorescence leakage in fluorescein angiography. Verteporfin (Visudine; Novartis, Basel, Switzerland) was infused at 6 mg/m 2 body surface area over 10 minutes, and then PDT was performed with a light fluence of 25 J/cm 2 by using a Visulus PDT system 690S (Carl Zeiss Meditec AG, Jena, Germany) 5 minutes after infusion completion.


Statistical analysis was performed by a multiple comparison using the Bonferroni method for changes in choroidal thickness in each sector after PDT and by the Dunnett test for the comparison of choroidal thickness between PDT-treated eyes and normal control eyes (SPSS software version 18.0; IBM Corp, Armonk, New York, USA). P values <.05 were considered statistically significant.




Results


A total of 22 patients (15 men and 7 women) who had 1 eye with active chronic CSC were enrolled. The mean age of the subjects was 55.0 ± 12.2 years. The mean duration of CSC prior to study entry was 8.9 ± 2.7 months (median, 8 months; range, 6–18 months). The leakage point locations observed by fluorescein angiography are shown in Table 1 . One month after reduced-fluence PDT treatment, subretinal fluid resolved completely in all 22 CSC patients, and there were no cases of recurrence during the study period.



Table 1

Patient Characteristics and Choroidal Thickness Before and After Reduced-Fluence Photodynamic Therapy in Eyes With Chronic Central Serous Chorioretinopathy
























































































































































































































































































































































































Case Age (y) Sex Affected Eye Duration of Central Serous Chorioretinopathy (mo) Leakage Point on Fluorescein Angiography Photodynamic Therapy Laser Spot Size (μm) logMAR Visual Acuity Choroidal Thickness, μm (Pretreatment) Choroidal Thickness, μm (6 Months)
Pretreatment 6 Months Center Inner Circle Outer Circle Center Inner Circle Outer Circle
1 46 M OD 6 Outer a superior 4900 0.05 −0.18 486 456 422 388 368 298
2 54 M OS 6 Inner b temporal 3800 −0.08 −0.18 545 436 343 260 257 237
3 53 M OD 7 Outer nasal 4950 0.00 −0.08 511 492 411 358 344 308
4 35 M OS 8 Inner temporal 4800 0.30 −0.06 533 524 466 357 350 326
5 47 F OD 9 Center 4100 0.22 0.22 365 367 322 319 334 312
6 51 M OD 10 Center 5100 0.22 0.22 527 509 461 458 444 397
7 51 M OS 11 Outer temporal 4050 −0.18 −0.18 526 508 453 538 511 429
8 41 M OD 12 Inner temporal 3450 0.40 0.10 580 543 431 366 350 307
9 47 M OD 6 Inner temporal 5300 0.00 0.00 368 365 332 250 256 255
10 55 M OD 7 Inner nasal 4850 0.10 0.05 259 258 227 253 248 232
11 42 M OD 7 Inner nasal 3850 0.00 −0.18 253 267 280 187 213 247
12 69 F OS 8 Center 4100 0.22 0.05 200 192 169 158 154 148
13 48 M OD 9 Inner nasal 5100 0.15 0.00 347 331 295 309 296 275
14 77 M OD 10 Outer nasal 5050 0.52 0.22 317 299 255 260 256 235
15 52 M OS 12 Inner inferior 4100 0.40 0.30 238 237 229 172 188 198
16 71 F OS 8 Outer superior 4350 0.52 0.00 306 304 299 236 233 244
17 67 F OD 9 Outer nasal 3300 0.05 0.00 277 282 292 334 333 315
18 52 M OD 7 Inner nasal 4600 0.22 0.10 345 337 307 217 224 233
19 73 F OS 8 Inner temporal 4600 0.70 0.30 534 417 310 329 320 289
20 64 F OD 18 Center 2250 0.15 0.00 396 369 305 341 322 270
21 41 M OS 7 Center 2500 0.10 −0.18 290 279 222 210 210 171
22 78 F OS 10 Outer nasal 5500 0.40 0.15 383 381 343 394 389 362

logMAR = logarithm of the minimal angle of resolution.

a Outer, 1.5–3 mm from the foveal center.


b Inner, 0.5–1.5 mm from foveal center.



Postoperative Photodynamic Therapy Changes in Choroidal Thickness


Eyes with chronic CSC showed thickened choroid in the macular area. However, choroidal thickness was reduced after reduced-fluence PDT. The mean center choroidal thickness (390.3 ± 116.3 μm prior to PDT) decreased to 278.1 ± 90.1 μm, 286.6 ± 82.2 μm, and 303.4 ± 92.3 μm ( P = .002, P = .005, and P = .026) at 1, 3, and 6 months post PDT, respectively ( Figure 3 ). In the inner circle there was also a significant decrease from baseline in choroidal thickness at 1, 3, and 6 months post PDT ( P = .03, P = .008, and P = .047, respectively). In the outer circle, however, there was a significant decrease from baseline in choroidal thickness at 1 and 3 months post PDT ( P = .005 and P = .02) but no significant difference from baseline choroidal thickness at 6 months ( P = .118).




Figure 3


Box-plot graphs of regional macular choroidal thickness before and after reduced-fluence photodynamic therapy in eyes with choronic central serous chorioretinopathy. (Left) Center choroidal thickness. (Middle) Inner-circle choroidal thickness. (Bottom) Outer-circle choroidal thickness. In the center and inner circle, the choroidal thickness was significantly decreased from baseline at 1, 3, and 6 months after treatment. The choroidal thickness in the outer circle was significantly decreased at 1 and 3 months after treatment. The difference was not statistically different at 6 months. NS = not significant. P < .01, ∗∗ P < .05, compared with pretreatment values.


Case Report


A 53-year-old man had visual disturbance in the right eye from chronic CSC. Extensive serous retinal detachment was seen in the macular area. Fluorescein angiogram showed diffuse leakages. Indocyanine green angiogram showed several areas of choroidal hyperpermeability and punctuate hyperfluorescent spots ( Figure 4 ). His choroidal thickness was 511 μm in the center, 492 μm in the inner circle, and 411 μm in the outer circle. The right eye was treated with reduced-fluence PDT to the areas of choroidal hyperpermeability. Serous retinal detachment resolved completely 1 month after the treatment. No recurrence was seen during the study period. The choroidal thickness decreased to 265 μm in the center, 334 μm in the inner circle, and 261 μm in the outer circle at 1 month post PDT. However, it gradually increased between 3 and 6 months; choroidal thickness increased to 358 μm in the center, 344 μm in the inner circle, and 308 μm in the outer circle at 6 months ( Figure 5 ).




Figure 4


A representative case with active chronic central serous chorioretinopathy. A 53-year-old subject had visual disturbance in the right eye from chronic central serous chorioretinopathy. (Right) Fluorescein angiogram shows diffuse leakages. (Left) Indocyanine green angiogram shows several areas of choroidal hyperpermeability and punctuate hyperfluorescent spots.

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Jan 7, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Change of Regional Choroid Thickness After Reduced-Fluence Photodynamic Therapy for Chronic Central Serous Chorioretinopathy

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