Choroidal Thickness Change in Central Serous Chorioretinopathy after Photodynamic Therapy Using Optical Coherence Tomography.
Central serous chorioretinopathy (CSC) is a sporadic disease that is characterized by serous neurosensory retinal detachment often affecting middle-aged men (1). Although it can heal spontaneously without treatment, it can show recurrent and chronic characteristics and lead to progressive visual loss (2).
A number of theories have been proposed concerning the pathophysiology of CSC, but its mechanism is still not fully understood. Theories related to retinal pigment epithelium (RPE) dysfunction and choroidal vessel abnormalities currently dominate the literature (3). In indocyanine green angiography (ICGA), it is stated that vascular anomalies in choroidal vessels, and increased venous dilation and hyperpermeability in patients with CSS, is more intense compared to RPE leakage (4).
Currently, monitorization, laser photocoagulation, anti-vascular endothelial growth factor (anti-VEGF) inhibitors, mineralocorticoid receptor antagonists, and photodynamic therapy (PDT) are applied for the treatment of CSC (3, 5-7). PDT has been shown to treat sub-retinal fluid accumulation and increase visual acuity (7). Although the treatment mechanism is unknown, it has been suggested that it reduces choroidal hyperpermeability, causing damage in the cho-riocapillaris and resulting in resolution of leakage in the RPE (8).
Optical coherence tomography (OCT) is a noninvasive diagnostic imaging technique that provides high-resolution and cross-sectional imaging of the retina and the choroid using light waves. Conventional spectral-domain OCT devices cannot adequately image the choroid layer due to the shadowing effect of the RPE and the choroidal vascular structure. Today, choroidal vascular structure can be visualized with the EDI-OCT technique developed by modification of the spectral-domain OCT technology (9). The choriocapillaris/Sattler's layer, which is known as the choroidal small and medium-sized vessel network just below the Bruch membrane, and the Haller's layers, which are composed of the larger vessels that are located more deeply, can be distinguished by using new technology devices.
Studies evaluating choroidal thickness with EDI-OCT have reported increased choroidal thickness in patients with CSC and decreased choroidal thickness in patients who spontaneously recovered, and in patients treated with PDT compared to healthy individuals (10, 11). In a study evaluating the choroidal sublayers with EDI-OCT, a significant increase was observed in the subfo-veal Haller's layer in patients with CSC compared to healthy subjects, but there was no change in the choriocapillaris/Sattler's layer (12). As far as we know, no study shows the effect of PDT on Haller's and Sattler's layers in patients with CSC.
This study intends to evaluate changes in the choroid layer, choriocapillaris/Sattler's and Haller's layers with EDI-OCT in patients with chronic CSC who have undergone PDT treatment.
Patients admitted to Ankara Ataturk Training and Research Hospital's Retina Clinic between March 2016 and September 2017 with a diagnosis of CSC were retrospectively reviewed on the basis of the file records. Patients who had symptoms of decreased visual acuity for a period of longer than six months receiving PDT treatment were included in the study. Patients with retinal diseases, such as age-related macular degeneration, degenerative myopia, polyp-oidal choroidal vasculopathy, and diabetic retinopathy, were excluded from the study. Patients with refractive errors of more than 6 diopters and patients with relapsed CSC who had previously undergone PDT and laser photocoagulation or intravitreal injection treatments were also excluded. Patients who did not attend regular follow-ups or have their EDI-OCT measurements were also excluded from the study. The diagnosis of CSC was made on the basis of subretinal fluid in the macular area in the OCT and idiopathic leaks detected via the fundus fluorescein angiography (FFA).
All patients received PDT at low energy levels according to the classical protocol (13). Verteporfin (Visudyne; Novartis, Basel, Switzerland) was calculated according to the body surface area of 6 mg/m (2) and administered intravenously for 10 min. After 15 min of beginning of the injection, the 689 nm diode laser was applied to the lesion site at a dose of 300 mW (half of the conventional dose of 600 mW) for 83 s.
During all control examinations, a detailed ophthalmologic examination including EDI-OCT measurements was performed on all patients. A visual acuity examination was performed with a Snellen eye chart. An FFA evaluation was performed on the first examination visit. The pre-PDT control examination records of patients and their post-PDT examination records at month 1 were evaluated.
A single technician performed the OCT measurements of the patients in the EDI mode using the Heidelberg spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) device. The same person (Mucella Arikan Yorgun) manually measured the choroidal thickness in the linear measurement mode of the device over the OCT section across the subfoveal area. After each measurement, the manual additions were deleted and the measurements were repeated three times at different times. The mean values were used for the analysis. Total choroidal, choriocapillaris/Sat-tler's layer, and Haller's layer measurements were performed at intervals of 500 urn and at a nasal and temporal distance of 1500 urn from the subfoveal point. The distance between the outer border of the retina pigment and the outer border of the choroidal vascular bed was accepted as the "total choroidal thickness" The innermost border of large choroid vessels and the space between the choroid-scleral line were recorded as "Haller's layer" The difference between the total choroidal thickness and Haller's layer was accepted as representing the "choriocapillaris/Sattler's layer" (Figure 1).
This study was conducted in accordance with the principles of the Helsinki Declaration and was approved by the Clinical Trials Ankara Ataturk Training and Research Hospital Ethics Committee Commission on 17.01.2018 with document no. 26379996/16. Written consent was obtained from all patients.
The Statistical Package for the Social Sciences 21.0 Windows version package program (SPSS IBM Corp.; Armonk, NY, USA) was used for the statistical analysis. The mean and standard deviation values of the data were calculated. The best corrected visual acuity (BCVA), measured with a Snellen eye chart, was converted to log MAR. The normal distribution of the data was tested with the Kolmogorov-Smirnov Test. The Student t test was used to compare quantitative data and Pearson's chi-square test was used to compare qualitative data. The p value of <0.05 was accepted as statistically significant. Thickness variations in the total choroid layer and Haller's and Sattler's layers after the photodynamic treatment were accepted as the evaluation criteria.
A total of 13 eyes of 13 patients who met the study criteria were included in the study. The average age was 49[+ or -]11 years (range 40-68). The number of female cases was 5 (38%) and the number of male cases was 8 (62%). The mean symptom duration was 21.6[+ or -]5.6 months. Complete relief of serous retinal detachment was observed in all patients following the first month post PDT treatment. The mean BCVA was 0.17[+ or -]0.13 log MAR before treatment and 0.18[+ or -]0.13 log MAR after treatment (p=0.16). The subfoveal total choroidal thickness before PDT was 310.60[+ or -]89.16 (range 214-454), and 308.41[+ or -]90.03 [micro]m after PDT (range 183-411) (p=0.048). The subfoveal Haller's layer thickness was 203.40[+ or -]86.37 [micro]m before PDT and 200.20[+ or -]81.55 [micro]m after the treatment (p=0.032). The Sattler's layer was 108.20[+ or -]33.75 [micro]m before PDT and 107.2[+ or -]17.03 [micro]m after the treatment (p=0.147). No significant differences were found in the mean values before and after PDT in the total choroidal thickness of the nasal and temporal areas, the thickness of the Haller's layer, and the thickness of the Sattler's layer (p>0.05). Total choroidal thicknesses, cho-riocapillaris/Sattler's layer thicknesses, and Haller's layer thickness values before treatment and one month after treatment are shown in Figure 2.
Today, developments in OCT technologies enable noninvasive measurement of choroidal thickness and indirect evaluation of choroidal vascular hyperpermeability, as well as investigation of the pathogenesis of diseases by distinguishing layers such as Haller's and Sattler's. In this study, in which subanalyzes of choroids and layers were performed with EDI-OCT, there was no significant change in the Sattler's layer, while a decrease in the thickness of the total choroid in the subfoveal area and the Haller's layer was detected during controls at month 1 in patients treated with PDT.
Two main theories have been proposed in the etiology of CSC: choroidal dysfunction and RPE dysfunction. In indocyanine green angiography studies, choroidal vascular anomalies causing choroidal hyperpermeability have been demonstrated (14). Choroidal hyperpermeability can be evaluated non-invasively by measuring the choroidal thickness in EDI-OCT studies. Imamura et al. (11) showed in their studies evaluating choroidal thickness with EDI-OCT that there was an increase in subfoveal choroidal thickness in patients with CSC compared to healthy individuals. Studies have reported that choroidal thickness is reduced in patients who recovered without treatment (11, 15). It is reported that there is no change in choroidal thickness in patients treated with laser, while the choroidal thickness decreases with PDT treatment (16). Maruko et al. (15) showed a reduction in the choroidal thickness with OCT in one month and a decrease in choroidal hyperpermeability with ICG in their study in which they followed up their patients with CSC who were administered a half-dose PDT for one year. Similarly, our study showed a decrease in the subfoveal choroidal thickening at month 1 after PDT treatment. Based on the results of these studies, it can be assumed that treatment with PDT causes a decrease in permeability by acting on the choroid, resulting in thinning of the choroid.
Dilatation in the choroidal vessels in the Haller's layer has been accepted as a descriptive feature of CSC disease agreed in the current literature as belonging to the group of "pachychoroid spectrum diseases" (17). Studies in which choroid layers have been evaluated by EDI-OCT showed dilation and increase in thickness of the impacted eye's vessels in the Haller's layer in CSC cases compared to the other eye and healthy subjects. It has been shown that the increase in choroidal thickness may be due to the enlargement of large choroidal vessels in the Haller's layer (8, 12, 18). No other study in the literature evaluates the choroidal lower layers using OCT after PDT treatment. However, in a study by Chan et al. (19) in which the choroidal layer was assessed through ICGA, a 32% reduction in the size of the dilated choroidal vessels was reported post-PDT in patients with CSC. In our study, a thinning of the subfoveal Haller's layer was observed after PDT treatment, but no change in the parafoveal choroidal thickness was detected. The smooth muscle cells present in the choroidal vessels are more dense in the area under the fovea and are affected by sympathetic and parasympathetic innervation, causing narrowing of the choroidal vessel wall. In the PDT protocol, the laser beam also acts on the parafoveal area circularly, as well as the subfoveal area. The lack of impact on the parafoveal area while reduction was seen in the choroidal thickness of the subfoveal area may be due to differences in the innervation and vessel network, which are more intense in the foveal area, rather than the direct effect of the laser beam.
The retrospective nature of our study, the small number of cases, and the short follow-up periods are the main limitations of the study. At the same time, even though the OCT device used contains an EDI mode, which provides high-resolution deep-screening, factors such as optical obstructions in front of the choroid layer, eye movements, and manual segmentation may have prevented optimal choroidal stratification. Although it has been used in some experimental studies with OCT devices that provide high penetration with a wavelength of >1000 nm (20), OCT devices, which we also use at our clinic, that enable penetration at an 840 nm laser wavelength are available. Finally, although the change in the choroidal thickness was statistically significant in our study, this change in choroidal thickness may not be clinically significant.
This study demonstrates that a decrease was observed in the subfoveal choroidal thickness and Haller's layer thickness with half-dose PDT treatment in patients with CSC. We think that the results of this study will shed light on the application of PDT mechanism on patients with CSC, whose etiopathogenesis is inadequately understood. Based on our current knowledge, no study in the literature shows the effect of PDT on Haller's and Sattler's layers in patients with CSC. In this regard, studies with a wide case series and a long follow-up period are needed.
Ethics Committee Approval: Ethics committee approval was received for this study from the Ethics Committee of Ankara Ataturk Training and Research Hospital (date: 17.01.2018, no. 26379996/16).
Informed Consent: Written informed consent was obtained from patients who participated in this study.
Peer-review: Externally peer-reviewed.
Conflict of Interest: The author has no conflicts of interest to declare.
Financial Disclosure: The author declared that this study has received no financial support.
(1.) lacono P, Battaglia Parodi M, Falcomata B, Bandello F. Central Serous Chorioretinopathy Treatments: A Mini Review. Ophthalmic Res 2015; 55: 76-83. [CrossRef]
(2.) Gulkaj S, Jahin O. Current therapeutic approaches to chronic central serous chorioretinopathy. Turk J Ophthalmol 2019; 49: 30-9. [CrossRef]
(3.) Gemenetzi M, De Salvo G, Lotery AJ. Central serous chorioretinopathy: an update on pathogenesis and treatment. Eye (Lond) 2010; 24: 1743-56. [CrossRef]
(4.) Quin G, Liew G, Ho IV, Gillies M, Fraser-Bell S. Diagnosis and interventions for central serous chorioretinopathy: review and update. Clin Exp Ophthalmol 2013; 41: 187-200. [CrossRef]
(5.) Goldhagen BE, Goldhardt R. Diagnosed a Patient with Central Serous Chorioretinopathy? Now What?: Management of Central Serous Chorioretinopathy. Curr Ophthalmol Rep 2017; 5: 141-8. [CrossRef]
(6.) Lee JY, Chae JB, Yang SJ, Kim JG, Yoon YH. Intravitreal bevacizumab versus the conventional protocol of photodynamic therapy for treatment of chronic central serous chorioretinopathy. Acta Oph-thalmol 2011; 89: e293-4. [CrossRef]
(7.) Ruiz-Moreno JM, Lugo FL, Armada F, Silva R, Montero JA, Arevalo JF, et al. Photodynamic therapy for chronic central serous chorioretinopathy. Acta Ophthalmol 2010; 88: 371-6. [CrossRef]
(8.) Van Rijssen TJ, Van Dijk EHC, Yzer S, Ohno-Matsui K, Keunen JEE, Schlingemann RO, et al. Central serous chorioretinopathy: Towards an evidence-based treatment guideline. Prog Retin Eye Res 2019; Jul 15. pii: S1350-9462(18)30094-6. [CrossRef]
(9.) Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol 2008; 146: 496-500. [CrossRef]
(10.) Kang NH, Kim YT. Change in subfoveal choroidal thickness in central serous chorioretinopathy following spontaneous resolution and low-fluence photodynamic therapy. Eye (Lond) 2013; 27: 387-91. [CrossRef]
(11.) Imamura Y, Fujiwara T, Margolis R, Spaide RF. Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy. Retina 2009; 29: 1469-73. [CrossRef]
(12.) Chung YR, Kim JW, Kim SW, Lee K. Choroidal Thickness In Patients With Central Serous Chorioretinopathy: Assessment of Haller and Sattler Layers. Retina 2016; 36: 1652-17. [CrossRef]
(13.) Chan WM, Lai TY, Lai RY, Tang EW, Liu DT, et al. Safety enhanced photodynamic therapy for chronic central serous chorioretinopathy: one-year results of a prospective study. Retina 2008; 28: 85-93. [CrossRef]
(14.) Jirarattanasopa P, Ooto S, Tsujikawa A, Yamashiro K, Hangai M, Hi-rata M, et al. Assessment of macular choroidal thickness by optical coherence tomography and angiographicchanges in central serous chorioretinopathy. Ophthalmology 2012; 119: 1666-78. [CrossRef]
(15.) Maruko I, Iida T, Sugano Y, Ojima A, Sekiryu T. Subfoveal choroidal thickness in fellow eyes of patients with central serous chorioreti-nopathy. Retina 2011; 31: 1603-8. [CrossRef]
(16.) Maruko I, Iida T, Sugano Y, Ojima A, Ogasawara M, Spaide RF. Subfoveal choroidal thickness after treatment of central serous chorioretinopathy. Ophthalmology 2010; 117: 1792-9. [CrossRef]
(17.) Dansingani KK, Balaratnasingam C, Naysan J, Freund KB. En face imaging of pachychoroid spectrum disorders with swept-source optical coherence tomography. Retina 2016; 36: 499-516. [CrossRef]
(18.) Yang L, Jonas JB, Wei W. Choroidal vessel diameter in central serous chorioretinopathy. Acta Ophthalmol 2013; 91: e358-62. [CrossRef]
(19.) Chan WM, Lam DS, Lai TY, Tam BS, Liu DT, Chan CK. Choroidal vascular remodelling in central serous chorioretinopathy after indocy-anine green guided photodynamic therapy with verteporfin: a novel treatment at the primary disease level. Br J Ophthalmol 2003; 87: 1453-8. [CrossRef]
(20.) Povazay B, Hofer B, Torti C, Hermann B, Tumlinson AR, Esmaeelpour M, et al. Impact of enhanced resolution, speed and penetration on three-dimensional retinal optical coherence tomography. Optics Express 2009; 17: 4134-50. [CrossRef]
Mucella Arikan Yorgun [iD]
Clinic of Ophthalmology, Ankara Ataturk Training and Research Hospital, Ankara, Turkey
Presented in: This study presented in the 19th Global Ophthalmology Summit, 26-27 February 2018, Berlin, Germany
How to cite: Arikan Yorgun M. Choroidal Thickness Change in Central Serous Chorioretinopathy after Photodynamic Therapy Using Optical Coherence Tomography. Eur J Ther 2019; 25(3): 189-92.
ORCID ID of the author: M.A.Y. 0000-0003-0069-2433
Corresponding Author: Mucella Arikan Yorgun E-mail: firstname.lastname@example.org
Received: 02.04.2018 * Accepted: 17.04.2018
|Printer friendly Cite/link Email Feedback|
|Title Annotation:||Original Research|
|Author:||Yorgun, Mucella Arikan|
|Publication:||European Journal of Therapeutics|
|Date:||Sep 1, 2019|
|Previous Article:||Effects of Regular Follow-up on Quality of Life and Warfarin Efficiency in Rural Patients.|
|Next Article:||Effectiveness of Percutaneous Drainage on the Treatment of Mesh-Induced Seroma.|