|Year : 2020 | Volume
| Issue : 1 | Page : 19-24
A clinical study of optical coherence tomography and fundus fluorescein angiography findings in central serous chorioretinopathy with co-relation to visual outcome in a tertiary care center of North-East India
Iva Rani Kalita1, Kabita Bora Baishya2, Harsh Vardhan Singh3
1 Department of Pediatric Ophthalmology, Fellow in Aravind Eye Hospital, Pondicherry, India
2 Regional Institute of Ophthalmology, Guwahati, Assam, India
3 Department of Retina-Vitreous, Fellow in Aravind Eye Hospital, Pondicherry, India
|Date of Submission||18-Jul-2020|
|Date of Acceptance||03-Aug-2020|
|Date of Web Publication||11-Dec-2020|
Dr. Iva Rani Kalita
Department of Pediatric Ophthalmology, Fellow in Aravind eye Hospital, Pondicherry-605007
Source of Support: None, Conflict of Interest: None
Purpose: The purpose is to identify the characteristic findings of central serous chorio-retinopathy (CSCR) on fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) in a tertiary care center of North-East India and to clinically correlate the final visual outcome with OCT values at the end of 6 months' follow-up. Methodology: A total of 70 cases (77 eyes) of CSCR were taken up for this prospective observational study. Other pathological causes of macular edema were excluded from the study. Visual acuity, OCT, and FFA were done in all cases at day 1 and were followed up till 6 months. OCT was done at each visit. Results: The mean age of the patient was 40 years (range 20–59 years, standard deviation [SD] 11.98). The day 1 mean vision was 0.72 logarithm of the minimum angle of resolution (log MAR), SD 0.30, P < 0.0001. The final mean vision at 6 months reduced to 0.22 Log MAR (SD = 0.1116 and P < 0.0001). The mean foveal thickness and macular volume (MV) was found to be 467.27 μm (SD 172.11) and 9.86 mm3 (SD 2.52), respectively, at day 1 of presentation, which reduced to 203.92 μm (SD 40.90; P = 0.0156) and 6.71 mm3 (SD 0.71; P = 0.0009, paired t-test) at the end of 6 months. Conclusion: Although the maximum visual recovery was attained at the 3rd month, cases with higher MV and foveal thickness at day 1 had poor final visual acuity. OCT alone can be helpful in determining the final visual outcome and the need for early therapy.
Keywords: Central serous chorioretinopathy, CSR, fundus fluorescein angiography, optical coherence tomography, visual outcome
|How to cite this article:|
Kalita IR, Baishya KB, Singh HV. A clinical study of optical coherence tomography and fundus fluorescein angiography findings in central serous chorioretinopathy with co-relation to visual outcome in a tertiary care center of North-East India. Egypt Retina J 2020;7:19-24
|How to cite this URL:|
Kalita IR, Baishya KB, Singh HV. A clinical study of optical coherence tomography and fundus fluorescein angiography findings in central serous chorioretinopathy with co-relation to visual outcome in a tertiary care center of North-East India. Egypt Retina J [serial online] 2020 [cited 2021 Jan 21];7:19-24. Available from: https://www.egyptretinaj.com/text.asp?2020/7/1/19/302998
| Introduction|| |
Central serous chorio-retinopathy (CSCR), most commonly known as “CSR,” is a sporadic disease of unknown etiology characterized by blister-like serous detachment of the neurosensory retina and retinal pigment epithelium in the posterior pole of the eye, usually involving the macula with angiographic retinal pigment epithelium leakage and choroidal hyperpermeability.,, The condition was first described by Von Graefe in 1866 as “relapsing central luetic retinitis.” In 1967 Gass termed it as “Idiopathic Central Serous Chorioretinopathy” (ICSC). CSCR is now being considered in “Pachychoroid clinical spectrum of disease” due to the changes that occur in choroidal thickness and vasculature.
So far, there is only one study reporting the incidence of this disease in the general population, which is found to be 1 case per year in every 22,000 inhabitants and it accounts for about 5% of the cases attending the retina specialist.
CSCR typically occurs in patients between the ages of 20–50 years, with the greatest incidence occurring in patients around 40 years of age. Recently, several cases >50 years of age had been reported. The cases reported by Schatz et al. were 60 years of age or older that did not have signs of age-related macular degeneration or macular disease. Probably, the youngest case was 7-year-old girl reported by Fine and Owens. The condition mostly affects males and overall incidence in men is approximately 5–10 times greater than females., In comparison to males, females develop the disease at an older age.
It is now a well-established fact that CSCR is a stress-related disease and people with Type A personality are more prone to this ailment., The study of Gelber and Schatz revealed severe disturbing psychological events preceding the acute onset of the disease in 91% of the cases. They found that 48% of their cases of CSCR had cardiovascular abnormalities. Other causes associated with CSCR are the use of steroids, sympathomimetics, anti-histaminic, alcohol, pregnancy and tobacco, untreated hypertension, multisystem autoimmune diseases, allergic respiratory disease, organ transplantation, and rarely endocrinal diseases like Cushing's.,,, The visual symptoms are blurring of vision; positive and negative central scotoma; micropsia; metamorphopsia; impaired color vision; blurred near vision; impaired night vision; spontaneous entoptic; light flashes; photophobia and impaired depth perception., Loss of contrast sensitivity is quite common, and this is usually expressed by the patients as dull vision.
CSCR is basically a self-limiting disease but can result in significant visual dysfunction that can persist even after macular fluid resolution. Historically, functional outcomes in clinical studies of retinal pathology typically rely on visual acuity as an outcome measure. However, acuity does not always reflect the quality of the visual function.
This study is carried out with the aim and objectives:
- Identifying the characteristic findings of CSCR on fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) in a tertiary care center of North-East India
- To clinically correlate the final visual outcome with OCT values at the end of 6 months' follow-up.
Secondary outcome: To find the common risk factors associated with CSCR in the study population.
| Methodology|| |
The present study was a prospective institutional-based observational study conducted in Regional Institute of Ophthalmology, Gauhati Medical College and Hospital, during the period of August 2016–July 2017. A total of 70 cases (77 eyes) of CSCR were taken up for this study. The study was approved by the Institutional Ethics Committee and followed all tenets of the Declaration of Helsinki.
Selection of patients
All patients attending the outpatient department of Regional Institute of Ophthalmology with the complaints of the dimness of vision and/or central haziness of vision were thoroughly screened. Patients with suggestive presenting complaints and history were subjected to further investigations for diagnosis and study of CSCR. Diagnosed cases of CSCR were enrolled in the study irrespective of age, sex, and clinical variation. After enrolment, the cases were clinically evaluated. Posterior segment findings with indirect ophthalmoscope and slit-lamp biomicroscopy using +90D lens were recorded, and then the patient was subjected to special investigations for confirmation of diagnosis and further management. All these cases of CSCR were observed for 6 months irrespective of the chronicity of the disease.
The patients with a clinical diagnosis of CSCR who had no contraindications to FFA were included.
Conditions mimicking CSCR such as diabetic maculopathy; traumatic macular edema; age-related macular degeneration; macular edema related to collagen vascular diseases; malignant hypertension; cystoid macular edema, etc. Media opacity that may impair the image quality of OCT.
A complete detailed history was taken, and due importance was given to the following points:
- Age, sex
- Details of the complains
- History of diabetes, hypertension, or any systemic diseases
- History of occupation, personal habits, stress, sleep deprivation
- Drug history, treatment history, pregnancy history in females
- Relevant family history.
Visual acuity of patients, including pin-hole vision, was recorded using Snellen's chart and Landolts C-chart for distance. The reduced Snellen's chart was used to record near vision. The distant vision was then converted in the logarithm of the minimum angle of resolution (LogMAR) notation using the Log MAR chart.
Direct and indirect ophthalmoscopy after full dilatation of the pupils was done, and the fundus findings were recorded. The indirect ophthalmoscope being a binocular system, gives a better stereoscopic view of the fundus.
A thorough examination of the anterior segment and the posterior segment was done with the slit lamp. The 90D lens was used to examine the posterior segment using both narrow and wide beams. The pattern of the beam and the presence of any form of abnormality in the macular area were noted.
Color vision test
The Ishihara chart was used to detect the presence of color defects.
The patients were asked to note any irregularity he saw on the grid and delineate the abnormality. The test was performed on both eyes for comparison.
Fluorescein angiography (FA) using the Zeiss Visucam fundus photograph camera was done with fully dilated pupils after receiving informed consent from the patient. Color and red-free photographs of the fundus in the area of concern were taken, following which 2cc of 20% fluorescein was injected intravenously. Keeping the barrier and exciting filter in place, early phase photographs were taken. A minimum of 1 picture was taken in 0–60 s, 1–2 min, and 2–4 min. The presence of leaks, their site, and pattern, and the presence of pigment epithelial detachment (PED) were recorded.
Optical coherence tomography
Using the third generation Stratus OCT, fast and regular macular thickness scans with the fovea at the center were taken. The height of serous detachment, the retinal thickness, the macular volume (MV), and any other abnormalities in the RPE were recorded. Line scans were taken at the site of leakage as well.
In addition to the above-mentioned tests, few laboratory investigations were also done to exclude any other underlying pathology and to clear the patient for fluorescein angiogram.
The patient's vision was noted on the day of presentation and was followed up at 3rd and 6th month, respectively, and the visual prognosis was noted on each visit. Fundus photo and OCT was used to monitor the patients during follow-up. Moreover, final visual acuity was recorded and compared.
The data were presented as the mean ± standard deviation (SD). The data were compared accordingly based on day 0, 3rd month, and 6th month findings. To compare MV and vision at day 0 and at 6th month, respectively, paired t-test was used. To find the correlation between the variables, Pearson's correlation of coefficient was applied. A P < 0.05 was considered to be statistically significant.
| Results|| |
In total, 70 patients (77 eyes) were enrolled in this study [Table 1]. The mean ([SD]) age of enrolled patients was 40 years (SD 11.98, range 20–59 years). The maximum number of patients was in the age group of 30–39 years (40%).
Out of 70 newly diagnosed cases of CSCR, 61 of them were male (87.14%) and 9 of them were female (12.86%), with a ratio of 6.8:1, which showed male preponderance. All 70 patients complained of general diminution of vision, 30 patients complained of central scotoma, 25 of distorted images, and 5 patients gave a history of headache and dull vision (due to the loss of contrast sensitivity), respectively [Table 1]. Most of the patients presented with multiple symptoms. Moreover, while asking about personal habits, most of them gave a history of less sleep (42.8%). Smoking and betel-nut consumption was found in 21.4% of patients each, and alcohol consumption was found in 14.4% [Table 1]. Hence, the most common associated risk factors of CSCR in our study were found to be sleep deprivation and stress. Our study showed bilateral (B/L) disease in 7 patients out of a total 70 (10%). Moreover, 10 patients out of a total of 70 (14.23%) had a history of recurrent attacks (two subjects with previous “2” episodes while rest 8 subjects had a history of “1” similar episode) in the past. Of these 10 patients, only 1 patient gave a history of treatment (both eyes focal laser), the rest all were treatment naïve cases. All these patients gave a positive history of stress and sleep deprivation. However, none of the patients had a history of any long-term steroid use in any form. Hence, stress has been found to be very strongly associated with bilaterality and recurrence of CSCR.
In our study, all 70 patients complained of general diminution of vision (100%); 4.3% complained of central scotoma, 35.7% complained of distorted images (metamorphopsia), and 7.14% patients gave a history of headache and dull vision (due to loss of contrast sensitivity), respectively. Most of the patients presented with multiple symptoms [Table 1].
Among the ocular findings, maximum cases showed sub-retinal fluid (SRF) collection (75.32%) on fundus examination. Forty eyes showed associated PED (51.95%). In our study, isolated PED was found in 3 eyes (3.9%). PEDs may vary in size, but they are usually < 0.25 disc diameter. They look like yellowish round-to-oval blister-like lesions. PED lying under CSCR is difficult to appreciate, and it needs FA for detection. In our study, we found sub-retinal precipitates in 16 eyes (20.78%), depigmented patch in 13 eyes (16.88%), pigment clumping in 1 eye (1.29%), and haemorrhagic CSCR in 2 eyes (2.60%). The color vision was found to be defective in 13 eyes (16.88%) out of a total 77 eyes [Table 2].
FFA was done in all 77 eyes. Eighty-seven percent of the cases showed a discrete spot of hyper-fluorescence at the level of RPE, of which 73% cases showed ink-blot pattern [Figure 1]c and [Figure 1]d and 14% showed smoke-stack pattern [Figure 1]a and [Figure 1]b, rest 13% showed diffuse leak [Figure 1]e and [Figure 1]f. Out of the 77 cases, ink-blot pattern was the most common. The FFA picture showed leakage mainly in four quadrant around the macula. Majority of the leakage were in superonasal quadrant (45.71%) followed by inferonasal quadrant (30%) and then superotemporal and inferotemporal quadrant [Table 2].
|Figure 1: Colored fundus photography images along with corresponding fundus fluorescein angiography picture showing various types of central serous chorioretinopathy. (a and b) Smoke-stack pattern in the right eye. (c and d) Ink-blot pattern in the left eye. (e and f) Diffuse leak pattern in the right eye|
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All patients were subjected to OCT, and moreover, it was used for quantitative assessment of MV during the follow-up period to see the resolution of SRF. Two different OCT patterns were observed in patients of CSCR: (1) the neurosensory detachment with well-defined reflection at the fluid–RPE interface (2) vaulted RPE spaces proving the presence of RPE detachment. The physiological foveal pit was present in almost all cases.
The day 1 vision of 77 eyes ranged from 6/9-hand movement (0.20–1.10 log MAR) with a mean vision of 0.72 log MAR, SD 0.30, P < 0.0001, which was significant. The maximum number of eyes presented with a vision ranging from 6/36 to 6/60 (log MAR 0.80–1.00) with a percentage of 50.65%. At 3 months, the mean vision was 0.33 Log MAR (range = 0.10–1.00, SD = 0.214) with maximum vision at range of 6/6–6/9 (Log Mar 0.10–0.20, 58.44%). Hence, there was a great visual improvement at 3 months of follow-up. The final vision was recorded to be ranging from 6/6 to 6/18 (Log MAR 0.10–0.50). The mean vision was 0.22 Log MAR (SD = 0.1116 and P < 0.0001). The study showed that the recurrent cases had a poor visual outcome in comparison to the new cases. The maximum vision that the recurrent cases (10) regained was 6/18 (Log MAR 1.50) [Table 3].
|Table 3: Comparison of mean vision, macular volume, foveal thickness at day 1, 3rd month, 6th month|
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The average foveal thickness among 70 patients (77 eyes) was found to be 467.27 μm (range 150–800 μm, SD 172.11) The average foveal thickness was divided into four groups (150–300 μm, 301–450 μm, 451–600 μm, and 601–750 μm, respectively) of which the maximum number of eyes (45 eyes, 58.44%) was found in the range of 451–600 μm on day 1 of presentation. The average foveal thickness reduced to 203.92 μm (range: 123–298 μm SD 40.90; P = 0.0156 paired t-test) at 6 months' follow-up [Table 3].
The average MV among 70 patients (77eyes) was found to be 9.86 mm3 (range 6.3–15.50 mm3 SD 2.52). The average MV was divided into five groups (6.00–7.90 mm3, 8.00–9.90 mm3, 10.00–11.90 mm3, 12.00–13.90 mm3, 14.00–15.90 mm3, respectively) of which the maximum number of eyes (29, 37.66%) was found in the range of 8.00–9.90 mm3 at day 1 of presentation. The average MV reduced to 6.71 mm3 (range 5.12–9.00; SD 0.71; P = 0.0009, paired t-test) at the end of 6 months follow-up [Table 3].
Among 77 eyes, PED could be detected in 40 eyes at day 0 (51.95%). Subsequent follow-up at 3 months showed PED in 34 eyes only (44.16%) and at 6 months it further reduced to 12 eyes only (15.58%). So, we could find that PED in CSCR is also self-resolving, and maximum resolution is seen at 6 months. PED could be found in 7 out of 10 recurrent cases. After all results were obtained we did a correlation study using Linear (Pearson) correlation study of vision with average foveal thickness and MV, respectively, and the results were highly significant (P < 0.0001) [Table 4].
|Table 4: Co-relation of visual outcome, macular volume, foveal thickness at day 1, 3rd month, 6th month|
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| Discussion|| |
After reviewing the voluminous literature on the etiology and pathogenesis of CSC, it certainly seems that CSC is a multifactorial disease. It appears to result from a complex interaction of known and unknown environmental and genetic factors. This ultimately leads to a B/L disease with systemic associations. In 1986, Yannuzzi, stated there was a lack of a definitive, universally accepted treatment for CSC. This could also be stated today. The multifactorial etiology and complex pathophysiology of the disease and its generally favorable natural history provide no clear proof of the necessity and long-term efficacy of any of the treatment choices. Many forms of therapies have been advocated, but it is said to be a benign disease with a tendency to recover spontaneously.
The mean age group of the present study was 40 years, which was similar to previous various studies of CSCR.,, Various studies proved that male shows a preponderance toward the disease 5–10 times more than female., We had a male: female ratio of 6.8:1. The incidence of B/L CSCR at the initial visit reported in literature is 5%–18%., The tendency of bilaterality was found to increase with long-term follow-up. Ten percent of our cases presented with B/L disease. Various studies have showed that most CSCR patients are hard-driven and tensed.,, It is now a well-established fact that CSCR is a stress-related disease, and people with Type A personality are more prone. Haimovici et al. hypothesized that medical and social factors having a stress-related component could be more prevalent among ICSC patients than controls. The most common associated risk factors of CSCR in our study was found to be sleep deprivation and stress. The acute form is characterized by the presence of SRF, clinically detectable on fundus examination and on OCT, with limited focal or multifocal RPE alterations that may be limited to small PEDs, and leakage through the RPE on FA. In our study, SRF was present in 58 eyes, 40 eyes showed associated PED (51.95%). Isolated PED was found in 3 eyes.
Ink-Blot pattern was the most common FFA findings like other studies., The cases (n = 10), in which FFA showed a diffuse leak pattern had poor recovery of final vision with vision not >6/36 (Log MAR 0.78) Those were the recurrent cases mainly and might suggest chronicity. Associated pigment clumping, hypopigmented patch were found in the recurrent cases, which are signs of chronicity. Hemorrhagic CSCR was found in two recurrent cases. Neovascularization is a recognized complication of CSCR. Although type 2 and type 3 neovascularization have been reported, Type 1 neovascularization is seen most frequently in this setting and is a sign of chronicity.
Straastma et al. reported the best-corrected visual acuity better than 6/9 (0.20 Log MAR) in 75% of the cases with an acute attack. In this study, the maximum patient regained vision of 6/6–6/9 (Log MAR 0.10–0.20) a 3-month follow-up itself. The foveal thickness and MV showed highly significant results when correlated with visual outcome. OCT foveal thickness at day 1 of >600 μm had a relatively poor final vision [Table 5]. The recurrent and B/L cases had poor visual outcome (maximum regained vision was 6/36–20/120, Log MAR 0.80) compared to others probably due to chronicity and loss of inner segment-outer segment (IS-OS) junction.
|Table 5: Foveal thickness (μm) and mean visual acuity at presentation and final visual recovery at 6-month follow-up|
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The recurrence rate of the cases could not be studied exactly because of the shorter follow-up time. Although we correlated the visual outcome with OCT findings such as foveal thickness and Central MV, we did not take into consideration the changes in IS-OS junction, external limiting membrane. The alteration of choroidal thickness and vasculature was also not studied.
| Conclusion|| |
We could conclude that the 1st day visual presentation has a prognostic significance in new or recurrent CSCR cases. OCT at the time of presentation alone can indicate the self-resolving nature of the disease, which otherwise might require interventions.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Cordes FC, Hogan MJ. Fluorescein angiography and the retinal pigment epithelium. Arch Ophth 1940;23:253.
Shakib M, Rutkowski P, Wise GN. Fluorescein angiography and the retinal pigment epithelium. Am J Ophthalmol 1972;74:206-218. doi:10.1016/0002-9394(72)90536-3.
Piccolino FC, Borgia L. Central serous chorioretinopathy and indocyanine green angiography. Retina 1994;14:231-42.
Verhoeff FH, Grossman HP, Herman P: Pathogenesis of juvenile disciform degeneration of the macula. Arch Ophthalmol 1937;18:561-585.
Gass JD. Pathogenesis of disciform detachment of the neuroepithelium. Am J Ophthalmol 1967;63:Suppl:1-139.
Warrow DJ, Hoang QV, Freund KB. Pachychoroid pigment epitheliopathy. Retina 2013;33:1659-72.
Kitzmann AS, Pulido JS, Diehl NN, Hodge DO, Burke JP. The incidence of central serous chorioretinopathy in Olmsted County, Minnesota, 1980-2002. Ophthalmology 2008;115:169-73.
Klein, BA. Symposium: Macular diseases. Clinical manifestations 1. Central serous retinopathy and choroidopathy. Trans Am Acad Ophthalmol 1965;69:614-22.
Schatz H, Madeira D, Johnson RN, McDonald HR. Central serous chorioretinopathy occurring in patients 60 years of age and older. Ophthalmology 1992;99:63-7.
Fine SL, Owens SL. Central serous retinopathy in a 7-year-old girl. Am J Ophthalmol 1980;90:871-3.
Castro-Correia J, Coutinho MF, Rosas V, Maia J. Long-term follow-up of central serous retinopathy in 150 patients. Doc Ophthalmol 1992;81:379-86.
Frederick AR Jr. Multifocal and recurrent (serous) choroidopathy (MARC) syndrome: A new variety of idiopathic central serous choroidopathy. Doc Ophthalmol 1984;56:203-35.
Haik GM, Perez LF, Murtagh JJ. Central serous retinopathy. Consecutive development in daughter and mother. Am J Ophthalmol 1968;65:612-5.
Yannuzzi LA. Type A behavior and central serous chorioretinopathy. Trans Am Ophthalmol Soc 1986;84:799-845.
Spahn C, Wiek J, Burger T, Hansen L. Psychosomatic aspects in patients with central serous chorioretinopathy. Br J Ophthalmol 2003;87:704-8.
Gelber GS, Schatz H. Loss of vision due to central serous chorioretinopathy following psychological stress. Am J Psychiatry 1987;144:46-50.
Gass JD. Central serous chorioretinopathy and white subretinal exudation during pregnancy. Arch Ophthalmol 1991;109:677-81.
Bouzas EA, Karadimas P, Pournaras CJ. Central serous chorioretinopathy and glucocorticoids. Surv Ophthalmol 2002;47:431-48.
Bujarborua D. Long-term follow-up of idiopathic central serous chorioretinopathy without laser. Acta Ophthalmol Scand 2001;79:417-21.
Eom Y, Oh J, Kim SW, Huh K. Systemic factors associated with central serous chorioretinopathy in Koreans. Korean J Ophthalmol 2012;26:260-4.
Burton TC. Central serous chorioretinopathy. In: Blodi E, editor. Current Concepts in Ophthalmology. Vol. 128. St Louis: CV; 1972. p. 3.
Yannuzzi LA, Shakin JL, Fisher YL, Altomonte MA. Peripheral retinal detachments and retinal pigment epithelial atrophic tracts secondary to central serous pigment epitheliopathy. Ophthalmology 1984;91:1554-72.
Spaide RF, Campeas L, Haas A, Yannuzzi LA, Fisher YL, Guyer DR, et al
. Central serous chorioretinopathy in younger and older adults. Ophthalmology 1996;103:2070-9.
Haimovici R, Koh S, Gagnon DR, Lehrfeld T, Wellik S; Central Serous Chorioretinopathy Case-Control Study Group. Risk factors for central serous chorioretinopathy: A case-control study. Ophthalmology 2004;111:244-9.
Gilbert CM, Owens SL, Smith PD, Fine SL. Long-term follow-up of central serous chorioretinopathy. Br J Ophthalmol 1984;68:815-20.
Spitznas M. Pathogenesis of central serous retinopathy: A new working hypothesis. Graefes Arch Clin Exp Ophthalmol 1986;224:321-4.
Abouammoh MA. Advances in the treatment of central serous chorioretinopathy. Saudi J Ophthalmol 2015;29:278-86.
Kim HC, Cho WB, Chung H. Morphologic changes in acute central serous chorioretinopathy using spectral domain optical coherence tomography. Korean J Ophthalmol 2012;26:347-54.
Pang CE, Freund KB. Pachychoroid neovasculopathy. Retina 2015;35:1-9.
Straastma BR, Allen RA, Pettit Th. Central serous retinopathy. Trans Pacif CST OTO Ophthalmol 1966;47:107-25.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]