**Purpose.**:
The purpose of the study was to determine which category of hydrodynamic phenomena the smokestack in central serous chorioretinopathy (CSC) most likely belongs to: leakage by diffusion or bulk flow.

**Methods.**:
Fluorescein angiograms of 13 eyes of 13 patients were reviewed and analyzed quantitatively. Two methods were used to assess the rate of fluid leakage. One was based on observation of the expansion rate of the bubble of stained fluid seen in the earliest phase of the angiogram, and the other one compared the area of the source of the leakage to the remaining area of retinal pigment epithelium (RPE) exposed to subretinal fluid, by using a standard value for RPE fluid resorption capacity per unit surface area and assuming that resorption equals leakage.

**Results.**:
The mean rates of leakage were 16.2 μL/mm^{2}/h (95% CI, 11.9–22.1) with the expanding-bubble method and 16.1 μL/mm^{2}/h (95% CI, 12.0–21.7) with the area-of-resorption method (*P* = 0.95, linear correlation *r* = 0.94). The repeatability coefficient for both methods was 36.3%.

**Conclusions.**:
The study demonstrated sufficient overall agreement between the two methods of assessing leakage rates in smokestack CSC, with adequate repeatability. Leakage rates of the RPE lesions in smokestack CSC occurred at rates consistent with bulk fluid flow, rather than secretion and diffusion, indicating that the primary source of leaking fluid was not the RPE, but a segment of underlying choroidal vasculature.

^{ 1,2 }

^{ 3 –5 }Except for the leakage site, the outer blood–retinal barrier is presumed to be intact in CSC, but it has been suggested that the metabolic active transport of fluid by the RPE is impaired and contributes to the formation and persistence of the serous detachment.

^{ 6,7 }

^{ 4,8 –12 }The present study evaluated two different methods of determining the type of inflow in acute smokestack CSC in an attempt to understand the process of pathologic fluid formation.

^{ 2 }Cases were excluded if the angiograms were of unacceptable quality or covered only some angiographic phases. OCT scans were available in only three cases and, being first-generation OCT scans, they were not of sufficient quality or multidirectionality to enable a reliable assessment of the volume of fluid under the retina. We therefore chose to base our analysis only on angiograms and fundus photographs, which were available in all cases. The confidentiality of the patients' information was protected, in compliance with the Declaration of Helsinki.

Patient | Sex | Age (y) | Affected Eye | BCVA (Snellen) |
---|---|---|---|---|

1 | M | 45 | Left | 0.7 |

2 | M | 34 | Right | 0.8 |

3 | M | 36 | Right | 1.0 |

4 | M | 41 | Left | 0.5 |

5 | M | 40 | Left | 0.4 |

6 | M | 44 | Right | 0.7 |

7 | M | 35 | Right | 0.9 |

8 | M | 39 | Left | 0.8 |

9 | M | 42 | Right | 0.3 |

10 | M | 33 | Right | 0.6 |

11 | M | 31 | Right | 1.0 |

12 | M | 58 | Left | 0.7 |

13 | M | 42 | Left | 1.0 |

*expanding-bubble*method (Figs. 1, 2) is based on the assumption that in the first phase of fluorescein angiographic leakage, freshly leaking fluid, densely stained by fluorescein, propagates into the subretinal cavity as a bubble that stands out in contrast to unstained surrounding fluid. Hence, the bubble can be seen to expand, from frame to frame in the angiography sequence, in proportion to the volumetric flow rate, the area of the source of leakage being defined as the area of the hotspot seen on the first frame of the angiogram and the relation between linear expansion and volume expansion being defined by where vol

_{1}is the volume (in cubic millimeters) of a hemisphere in the first frame of the angiogram: ( $ 4 3 $ × π ×

*r*

^{2})/2; vol

_{2}is the volume (in cubic millimeters) of a hemisphere in the second frame of the angiogram, according to the same formula; Δ

*t*is the time elapsed between the recording of the two angiograms; and area is the area (in square millimeters) of the source of leakage in the first frame of the angiogram (area = π

*r*

^{2}).

*area-of-resorption*method (Figs. 3, 4) is based on the assumption that a serous neurosensory detachment of stable size is maintained by the equilibrium between inflow (leakage) from a circumscribed source of leakage and outflow (resorption) through a surrounding area of RPE that has been exposed by leaking fluid, opening and expanding a cavity between the retina and the RPE to the point that equilibrium between leakage and resorption is established. The model assumes that the retina is not involved in the production or resorption of subretinal fluid. The rate by which the RPE resorbs subretinal fluid has been found to be 0.12 μL/mm

^{2}/h in rabbits in which the rate of disappearance of fluid injected under the retina was observed.

^{ 13 }Because no comparable observations are available in humans, we have assumed that the data apply to humans with smokestack CSC, except at the point of leakage. The extent of the serous retinal detachment was determined by fitting of an oval overlying the rim of the retinal detachment, as seen on a late-phase fluorescein angiogram, and measuring its area. The rate of leakage was defined by where area

_{1}is the area of the source of leakage on the earliest angiogram, area

_{2}is the area of detached retina minus the source of leakage, and resorption rate is 0.12 μL/mm

^{2}/h.

*t*-test and linear regression and after back-transforming into the original scale. The results are given in the original scale. Intraobserver reproducibility was determined by using repeatability coefficients

^{ 14 }and is expressed as a mean percentage of all measurements. Comparison between methods is shown in a Bland-Altman plot (see Fig. 6), equivalent to the log transformation used elsewhere. The difference between methods in the Bland-Altman plot is given as the ratio of the methods. The level of statistical significance was set at

*P*< 0.05 (SPSS PC 12.0 software; SPSS Inc., Chicago, IL).

^{2}. The serous retinal detachment was circular or nearly circular in all cases, and no case showed subretinal granules, gravitational tracts, or other signs of chronic CSC.

^{2}/h with a mean of 16.2 μL/mm

^{2}/h) for the expanding-bubble method and 36.3% (corresponding to 95% CI, 5.87–44.3 with a mean of 16.1 μL/mm

^{2}/h) for the area-of-resorption method. Because of the moderate level of repeatability, subsequent results are based on the mean of triplicate results.

^{2}/h (95% CI, 11.9–22.1) and 16.1 μL/mm

^{2}/h (95% CI, 12.0–21.7) by the area-of-resorption method (

*P*= 0.95, paired

*t*-test on log-transformed data; Table 2). The correlation between the two methods was

*r*= 0.94 (Fig. 5). A Bland-Altman plot of mean leakage rates showed an even distribution around a horizontal line, with a mean ratio between the methods of 1.06 and 95% CI, 0.41–1.70 (

*P*= 0.52; paired

*t*-test; Fig. 6).

Patient | Expanding Bubble Method | Area of Resorption Method | ||
---|---|---|---|---|

Mean (μL/mm^{2}/hr) | 95% CI | Mean (μL/mm^{2}/hr) | 95% CI | |

1 | 11.5 | 5.69–23.3 | 22.1 | 3.29–148.1 |

2 | 5.46 | 3.53–8.46 | 7.12 | 3.07–16.5 |

3 | 18.4 | 1.82–186.8 | 18.3 | 5.32–63.3 |

4 | 8.25 | 5.06–13.5 | 6.27 | 3.44–11.4 |

5 | 12.5 | 7.21–21.5 | 12.5 | 4.11–37.8 |

6 | 6.64 | 2.17–20.4 | 9.23 | 4.94–17.2 |

7 | 197.3 | 96.0–405.4 | 151.2 | 78.2–292.4 |

8 | 16.0 | 9.31–27.5 | 9.20 | 4.03–21.0 |

9 | 11.4 | 3.78–34.2 | 11.7 | 8.17–16.7 |

10 | 11.3 | 6.28–20.5 | 8.81 | 4.15–18.7 |

11 | 39.8 | 34.7–45.7 | 37.3 | 30.3–45.8 |

12 | 12.7 | 7.48–21.6 | 11.8 | 5.16–27.1 |

13 | 32.9 | 21.6–50.1 | 38.2 | 22.6–64.7 |

Total | 16.2 | 11.9–22.1 | 16.1 | 12.0–21.7 |

^{2}/h with the respective methods, case 7 was the only one that reached rates higher than 40 μL/mm

^{2}/h (Table 2). A review of the fluorescein angiogram revealed no sign of a retinal pigment epithelial tear. OCT was unavailable.

^{ 15 –19 }The rates of leakage observed in this study exceeded more than one order of magnitude those known from the choroidal plexus, which secretes cerebrospinal fluid at a rate of 0.48 μL/mm

^{2}/h.

^{ 20 }This finding indicates that smokestack leakage in CSC represents bulk flow, rather than secretion by the RPE. Obviously, the angiographic sources of leakage need not represent the primary source of the leakage. It may simply be a bottleneck in a conduit for convective fluid flow that funnels fluid originating from a larger source behind the RPE into the subretinal space. The existence of such a source is suggested by several findings. First, fluorescein angiographic leakage in CSC often occurs in relation to pigment epithelial detachment, which could be driven by fluid pressure from behind Bruch's membrane. Second, indocyanine green angiography in CSC sometimes shows localized delayed choroidal filling with subsequent choroidal vascular staining and leakage. These observations indicate the presence of choroidal vasculopathy in relation to CSC-lesions of the RPE, a vasculopathy that may be the primary cause of CSC.

^{ 21,22 }

^{ 23 }We considered the potential role of diffusion in producing the early concentric expanding bubble. The concentration of fluorescein in a serous detachment was estimated with a mathematical model, based on Fick's law of diffusion, assuming a constant concentration at the pore of inflow and a diffusion rate of 6 × 10

^{−6}cm

^{2}/s. The diffusion gradient throughout the detachment was assessed with several hemispheric cells, all a radius of 10 μm, and diffusion occurred bidirectionally. No active transport through the RPE was included. The model indicates that approximately 20% of the observed flow may be attributable to diffusion. Diffusion is driven only by osmotic gradients, presumably uniform in the serous detachment, and as the observed volume flow is larger than the flow from diffusion, we still believe that the smokestack phenomenon represent additional bulk flow. The observed upward direction of flow in smokestack CSC may be caused by differences in density or thermal gradients between newly formed fluid and fluid that has remained longer in the subretinal cavity.

^{ 24 }

^{ 25 }but we favor the data from the rabbit experiments because the extent of the area of detachment and other methodologic aspects were better defined than in the more pragmatic clinical observations made in humans. Another issue is that the RPE may be diffusely dysfunctional in CSC,

^{ 7 }with the dysfunction potentially including an impaired capacity to resorb subretinal fluid because of metabolic dysfunction or abnormal hydrostatic pressure in the choroid. We cannot entirely exclude this possibility, but it is worth noting that all our cases had small, focal smokestack lesions and a short duration of symptoms and no case had the more extensive RPE abnormalities associated with chronic CSC.

^{ 26 }Clinical observation of the precipitation of macromolecules within and underneath the retina after closure of vascular leakage strongly suggests that the RPE can overcome osmotic drag.

^{ 27 }

^{ 28 }It remains to be determined, by detailed OCT examination of smokestack leakage in CSC, whether a tear in the RPE is an essential or an occasional feature of this condition.

^{ 29,30 }