Japanese Journal of Ophthalmology

, Volume 57, Issue 3, pp 275–282 | Cite as

Branch retinal vein occlusion-associated subretinal hemorrhage

  • Yuki Muraoka
  • Akitaka Tsujikawa
  • Tomoaki Murakami
  • Ken Ogino
  • Kazuaki Miyamoto
  • Nagahisa Yoshimura
Clinical Investigation

Abstract

Purpose

To study the pathomorphology of subretinal hemorrhage (SRH) seen in eyes with branch retinal vein occlusion (BRVO) and its association with visual prognosis.

Methods

We retrospectively reviewed 42 consecutive patients (42 eyes) with BRVO that affected the fovea. Retinal structural changes were examined by spectral domain optical coherence tomography (SD-OCT).

Results

On SD-OCT sections, serous retinal detachment was seen at the fovea in 35 eyes, 18 of which accompanied foveal SRH. While initial detection of foveal SRH had no correlation with initial visual acuity (VA), it was correlated with poorer final VA (r = 0.361, P = 0.019). Our patients were classified into two groups by the initial detection of foveal SRH, and initial VA was not different between these two groups. At the final examination, damaged lengths in the foveal photoreceptor layer were significantly longer in the SRH-positive group than those in the SRH-negative group (P = 0.004), and final VA in the SRH-positive group was significantly worse than that in the SRH-negative group (P = 0.019).

Conclusion

Foveal SRH is not an uncommon feature in BRVO and may cause subsequent damage to the foveal photoreceptor layer, resulting in poor visual function.

Keywords

Branch retinal vein occlusion Subretinal hemorrhage Photoreceptor damage Spectral-domain optical coherence tomography 

Introduction

Branch retinal vein occlusion (BRVO), one of the most common vascular occlusive diseases of the retina [1, 2, 3], is caused by a retinal circulatory disturbance in a main trunk of the retinal veins. Acute BRVO is characterized by flame-shaped retinal hemorrhage and venous engorgement in the affected retina, often with macular edema. In eyes with acute BRVO, visual acuity (VA) often decreases because of the macular edema, which can be clinically diagnosed based on fundus examination, fluorescein angiography and/or optical coherence tomography (OCT). A number of treatments are now used for the regression of the macular edema, including intravitreal injections of anti-vascular endothelial growth factor agents [4, 5, 6, 7].

Recent technologic advances in OCT revealed that the retinal morphological changes in BRVO exist not only in the inner retina but in the outer aspects, occasionally even in the subretinal spaces [8, 9, 10, 11, 12]. Yamaike et al. [10] report that macular edema associated with acute BRVO consists of cystoid spaces in various retinal layers and marked retinal swelling especially in the retinal outer layers. Serous retinal detachment (SRD) is also often accompanied at the BRVO-affected fovea [8, 11, 13, 14]. In addition, recent OCT studies reveal that visual function correlates with the integrity of the foveal photoreceptor layer, i.e., the junction between inner and outer segments of the photoreceptors (IS/OS) [15, 16, 17, 18, 19] and the external limiting membrane (ELM) [20, 21]. Murakami et al. [22] report that in resolved macular edema with BRVO, the condition of the foveal IS/OS was correlated with VA. However, there is little information on which pathology in acute BRVO determines the integrity in foveal photoreceptors after the resolution of the retinal hemorrhage and retinal thickening [23].

With detailed fundus examination by slit-lamp biomicroscopy, clinicians sometimes find the BRVO-affected eyes showing hemorrhage within foveal cystoid spaces and/or subretinal space [8, 9, 11]. In eyes with BRVO, while the hemorrhage is rarely seen in the retinal inner surface at the foveal center, subretinal hemorrhage (SRH) is located just at the fovea, which may cause damage to the foveal photoreceptors [8, 9, 24]. However, the reports about characteristic and clinical relevance of BRVO-induced SRH are scant [23, 24]. In the current study, we elucidated the clinical characteristics of SRH in eyes with BRVO and their correlations with the morphologic and functional changes of foveal photoreceptors by examining OCT images captured between the acute and chronic phases.

Subjects and methods

For this observational case study, we retrospectively reviewed the medical records of 42 consecutive patients (42 eyes) with acute BRVO who were seen by members of the Department of Ophthalmology at Kyoto University Hospital between June 2008 and January 2011. Inclusion criteria included (1) symptomatic BRVO, in which retinal hemorrhage and retinal edema extended to the macula, (2) foveal thickness measured by SD-OCT greater than 250 μm at the initial visit, (3) duration of symptoms until initial examination less than 3 months, and (4) a minimum follow-up of 6 months after the initial visit. The diagnosis of BRVO was based on fundus examination and fluorescein angiography findings by two retina specialists (AT, TM). Eyes with central retinal vein occlusion or hemi-central retinal vein occlusion were excluded from the current study. Eyes with co-existing ocular disease (i.e., epiretinal membrane, glaucoma, diabetic retinopathy or senile cataract that resulted in poor quality SD-OCT images) and eyes that had been treated previously for BRVO were also excluded. Of the 42 eyes included in the present study, 12 were treated with grid laser photocoagulation, 5 underwent pars plana vitrectomy for treatment of their macular edema during follow-up, and the remaining 25 eyes received no treatment. The current study was approved by the Institutional Review Board at Kyoto University Graduate School of Medicine and adhered to the tenets of the Declaration of Helsinki.

At the initial examination, each patient underwent a comprehensive ophthalmologic examination, which included measurement of best-corrected VA with a Landolt chart, determination of intraocular pressure, indirect ophthalmoscopy, slit-lamp biomicroscopy with a non-contact lens and SD-OCT examination. To assess retinal perfusion status, each patient underwent fluorescein angiography with a confocal laser scanning system (HRA-2, Heidelberg Engineering, Heidelberg, Germany). Eyes with BRVO were classified as ischemic when the area of nonperfusion was greater than five disc diameters in size. In addition, the entire macular region was examined with Spectralis HRA+OCT (Heidelberg Engineering).

Using the initial SD-OCT images, we performed quantitative measurements and morphologic evaluations at the fovea. Foveal thickness was defined as the mean distance between the vitreoretinal interface and retinal pigment epithelium within a circle measuring 1 mm in diameter centered on the fovea. Using these data, the cystoid spaces, SRD and SRH of each patient were judged to have been either within or without the foveal area. Whenever foveal cystoid spaces were seen, they were examined to establish whether they were hemorrhaging. To assess the integrity of the foveal outer retina, we examined the condition of the ELM line and of the IS/OS line in the foveal area. Evaluations of the foveal ELM and IS/OS were performed within the central 1-mm area of the fovea using gray-scale vertical OCT images. The statuses of the foveal ELM line and of the IS/OS line were classified as being complete if the complete line could be detected in the central 1 mm area of the fovea or as being incomplete if not.

Each patient underwent a second comprehensive ophthalmologic examination, including measurement of the best-corrected VA, indirect ophthalmoscopy, slit-lamp biomicroscopy with a non-contact lens and OCT examination with the Spectralis HRA+OCT. Fluorescein angiography was performed if deemed necessary. Using SD-OCT images at the final examination of each follow-up period (14.8 ± 5.4 months, 6–28 months), we performed the same quantitative measurements and morphologic evaluations within the foveal area as had been performed previously. In addition, we measured the defect lengths seen in the ELM line or in the IS/OS line within the central 1-mm area on vertical and horizontal SD-OCT scans; this was done with the software that was built into the Spectralis HRA+OCT.

Statistical analysis was performed using PASW Statistics, version 18.0 (SPSS, Chicago, IL, USA). All values are presented as mean ± standard deviation. For statistical analysis, VA measured with a Landolt chart was converted to a logarithm of the minimum angle of resolution (logMAR). Analysis of the two groups was done using the Student’s t test, and bivariate relationships were analyzed using the Pearson’s correlation coefficient. A stepwise forward multivariate linear regression analysis was performed to evaluate the contribution made by each initial factor to the final VA. A P value of less than 0.05 was considered to be statistically significant.

Results

In the current study, 42 eyes of 42 patients (23 women and 19 men) with BRVO, ranging in age from 42 to 83 years (64.9 ± 10.1 years), were examined. Table 1 shows initial measurements of all patients who were eligible for inclusion in this study.
Table 1

Initial and final conditions of eligible patients with branch retinal vein occlusion

Age (years)

64.9 ± 10.1 (42 to 83)

Gender (women/men)

23/19

Duration of symptom until initial examination (weeks)

3.9 ± 2.9 (0.4 to 9.9)

Follow-up (months)

14.9 ± 5.4 (6 to 28)

Initial examination

 Visual acuity (logMAR)

0.44 ± 0.35 (0 to 1.22)

 Foveal thickness (μm)

557.8 ± 156.8 (296 to 886)

 Foveal cystoid spaces

34

 Hemorrhage within foveal cystoid spaces

19

 Foveal SRD

35

 Foveal SRH

18

 Status of foveal ELM (complete/incomplete)

14/28

 Status of foveal IS/OS (complete/incomplete)

9/33

 Retinal perfusion status (ischemic/non-ischemic)

28/14

Final examination

 Visual acuity (logMAR)

0.24 ± 0.33 (−0.18 to 1.1)

 Foveal thickness (μm)

365.5 ± 137.2 (227 to 791)

 Status of foveal ELM (complete/incomplete)

21/21

 Status of foveal IS/OS (complete/incomplete)

17/25

 Vertical defect length in foveal ELM (μm)

135.0 ± 195.4 (0 to 810)

 Horizontal defect length in foveal ELM (μm)

183.4 ± 286.5 (0 to 1000)

 Vertical defect length in foveal IS/OS (μm)

283.2 ± 312.8 (0 to 1000)

 Horizontal defect length in foveal IS/OS (μm)

237.0 ± 299.6 (0 to 1000)

logMAR logarithm of the minimum angle of resolution, SRD serous retinal detachment, SRH subretinal hemorrhage, ELM external limiting membrane, IS/OS junction between inner and outer segments of the photoreceptors

At the initial visits, all eyes showed intraretinal hemorrhage and macular thickening; mean foveal thickness was 557.8 ± 156.8 μm. Of the 42 eyes, cystoid spaces were seen in 34 eyes and SRD at the fovea in 35 eyes. Fundus examination revealed hemorrhage within subretinal spaces and/or foveal cystoid spaces in some eyes; this was detected more sensitively on OCT images. On OCT sections, 19 of the 34 eyes had foveal cystoid spaces with hemorrhage within these spaces; hemorrhage within the foveal cystoid spaces often made a niveau formation and occasionally appeared as amorphous hyperreflectivity (Fig. 1). Eighteen of the 35 eyes with foveal SRD accompanied SRH within the subretinal space; the SRH appeared as homogenous hyper-, or, as amorphous mild to moderate hyperreflectivity (Fig. 1). Sequential OCT sections of the affected fovea demonstrated that the hemorrhage within foveal cystoid spaces connected to the SRH through the external boundary of the retina in some eyes (Fig. 2). Of the 18 eyes with SRH at the fovea, 16 showed hemorrhage within the foveal cystoid spaces.
Fig. 1

Hemorrhage within the foveal cystoid spaces and subretinal hemorrhage associated with branch retinal vein occlusion. a Magnified fundus photograph shows a retinal hemorrhage in the shape of a meniscus at the fovea (arrowheads) (66-year-old woman, 0.4 OD). b In a vertical section through the fovea obtained with optical coherence tomography, this retinal hemorrhage shows a niveau formation within a large foveal cystoid space (short arrow). Subretinal hemorrhage is also seen at the fovea (long arrow). c Magnified fundus photograph shows superficial retinal hemorrhage with subretinal hemorrhage at the fovea (arrowheads) (76-year-old woman, 0.3 OS). d Vertical section through the fovea obtained with optical coherence tomography shows subretinal hemorrhage seen on the fundus photograph as intense homogenous hyperreflectivity (arrow) in the subretinal space. Yellow arrow shows foveal center in each eye

Fig. 2

Subretinal hemorrhage connected to hemorrhage within a foveal cystoid space (70-year-old man, 0.5 OS). Fundus photograph (a) and fluorescein angiogram (b) show the retinal hemorrhage associated with branch retinal vein occlusion. Oblique (c) and horizontal (d) sections obtained with optical coherence tomography along white arrows shown in the angiogram show hemorrhage within a foveal cystoid space (short arrows) and subretinal hemorrhage (long arrows). Subretinal hemorrhage appears to be connected to the hemorrhage within the foveal cystoid spaces through the external boundary of the neurosensory retina

Table 2 shows the association of initial VA with other measurements at the initial visits. At the initial examination, foveal ELM was completely seen in 14 and IS/OS, in 9 eyes. Although the detection of the foveal IS/OS line showed only a marginal correlation with initial VA (r = 0.261, P = 0.095), the detection rate of foveal ELM showed a more obvious correlation with initial VA (r = 0.366, P = 0.017).
Table 2

Association of initial visual acuity with other measurements obtained at initial examination

 

r

P value

Age (years)

0.232

0.139

Duration of symptom (weeks)

0.088

0.580

Foveal thickness (μm)

0.206

0.202

Foveal cystoid spaces

0.152

0.338

Hemorrhage within foveal cystoid spaces

0.243

0.121

Foveal SRD

0.109

0.454

Foveal SRH

0.109

0.490

Status of foveal ELM

0.366

0.017

Status of foveal IS/OS

0.261

0.095

Retinal perfusion status

0.093

0.561

SRD serous retinal detachment, SRH subretinal hemorrhage, ELM external limiting membrane, IS/OS junction between inner and outer segments of the photoreceptors

At the final visits, VA had improved significantly to 0.21 ± 0.33 (P = 0.002), and macular edema was substantially reduced; foveal thickness was decreased to 365.5 ± 137.2 μm (range 227–791 μm) (P < 0.001). In parallel with resolution of the macular edema, the integrity of the foveal photoreceptor layers were recovered; the ELM and IS/OS lines at the fovea were completely detected in 21 and 17 eyes, respectively. Table 3 shows the association of final VA with the other measurements at the final visits. Better final VA was linearly correlated with less foveal thickness (r = 0.358, P = 0.027) and a higher detection rate of foveal ELM (r = 0.419, P = 0.006) and the IS/OS line (r = 0.565, P = 0.002). Furthermore, the defect lengths in the ELM and IS/OS lines were correlated most closely with poor final VA (r = 0.532, P < 0.001; r = 0.543, P < 0.001).
Table 3

Association of final visual acuity with other measurements obtained at final examination

 

r

P value

Age (years)

0.359

0.020

Duration from initial symptoms (months)

−0.059

0.712

Foveal thickness (μm)

0.358

0.027

Status of foveal ELM

0.419

0.006

Status of foveal IS/OS

0.465

0.002

Vertical defect length in foveal ELM (μm)

0.532

<0.001

Vertical defect length in foveal IS/OS (μm)

0.543

<0.001

ELM external limiting membrane, IS/OS junction between inner and outer segments of the photoreceptors

Table 4 shows associations of the final VA with the initial visit measurements. Five factors at the initial examinations including foveal thickness (r = 0.496, P < 0.001) and presence of hemorrhage within the foveal cystoid spaces (r = 0.459, P = 0.002) and SRH (r = 0.361, P = 0.019) were significantly correlated with poorer final VA by simple regression analysis. We thus investigated the association of these five independent factors with the final VA by multiple regression analysis. Initial foveal thickness was closely (ß = 0.374, P = 0.006) and initial detection of foveal SRH was marginally correlated with the final VA (ß = 0.279, P = 0.061).
Table 4

Association of final visual acuity with measurement values obtained at initial examination

 

Single regression analysis

Multiple regression analysis

 

Regression coefficient

P value

Partial regression coefficient

P value

Age (years)

0.365

0.017

0.232

0.090

Durations of symptom until initial examination (weeks)

−0.139

0.381

Visual acuity (logMAR)

0.329

0.033

0.154

0.233

Foveal thickness (μm)

0.496

<0.001

0.374

0.006

Foveal cystoid spaces

0.290

0.063

Hemorrhage within foveal cystoid spaces

0.459

0.002

0.160

0.302

Foveal SRD

0.164

0.298

Foveal SRH

0.361

0.019

0.279

0.061

Status of foveal ELM

0.219

0.163

Status of foveal IS/OS

0.258

0.100

Retinal perfusion status

0.186

0.245

logMAR logarithm of the minimum angle of resolution, SRD serous retinal detachment, SRH subretinal hemorrhage, ELM external limiting membrane, IS/OS junction between inner and outer segments of the photoreceptors

Therefore, our patients were classified into one of two groups depending on whether foveal SRH was detected at the initial examination or not (Table 5). Although the initial VA was not different between the two groups (P = 0.490), the final VA (0.37 ± 0.35, range −0.08 to 1.10) in the SRH-positive group was significantly worse than that (0.14 ± 0.27, range −0.18 to 0.30) in the SRH-negative group (P = 0.019). In addition, the vertical and horizontal defect lengths in the foveal IS/OS line of the SRH-positive group were significantly longer than those of the SRH-negative group (P = 0.004, P = 0.028, respectively). In the foveal ELM, the horizontal defect length was longer than in the SRH-negative group (P = 0.017) (Table 5; Fig. 3).
Table 5

Comparisons of initial visual acuity and final measurement values between two groups classified by initial detection of foveal subretinal hemorrhage

 

Initial subretinal hemorrhage

(−)

24 eyes

Initial subretinal hemorrhage

(+)

18 eyes

P value

Mean ± SD

Range

Mean ± SD

Range

Initial visual acuity (logMAR)

0.41 ± 0.37

0 to 1.05

0.49 ± 0.32

0.05 to 1.22

0.490

Final visual acuity (logMAR)

0.14 ± 0.27

−0.18 to 0.30

0.37 ± 0.35

−0.08 to 1.10

0.019

Final foveal thickness (μm)

342.3 ± 105.0

225 to 628

399.5 ± 172.5

227 to 791

0.218

Vertical defect length in foveal ELM (μm)

88.6 ± 149.3

0 to 550

194.4 ± 233.1

0 to 810

0.085

Horizontal defect length in foveal ELM (μm)

87.0 ± 197.0

0 to 800

301.1 ± 337.2

0 to 1000

0.017

Vertical defect length in foveal IS/OS (μm)

163.3 ± 286.1

0 to 1000

436.3 ± 282.8

0 to 1000

0.004

Horizontal defect length in foveal IS/OS (μm)

88.6 ± 149.3

0 to 800

194.4 ± 233.1

0 to 1000

0.028

logMAR logarithm of the minimum angle of resolution, ELM external limiting membrane, IS/OS junction between inner and outer segments of the photoreceptors

Fig. 3

Damage to the foveal outer retina associated with subretinal hemorrhage from branch retinal vein occlusion (53-year-old woman, 0.3 OS). a Initial fundus photograph shows superficial retinal hemorrhage associated with acute branch retinal vein occlusion. Neither hemorrhage within the foveal cystoid space nor subretinal hemorrhage is obvious. b A vertical section through the fovea obtained with optical coherence tomography (OCT) reveals hemorrhage within the foveal cystoid space (short arrow) and subretinal hemorrhage (long arrow). c Fundus photograph taken 16 months after initial examination shows complete absorbance of the retinal hemorrhage (0.6 OS). Vertical (d) and horizontal (e) OCT sections through the fovea confirm complete absorption of the macular edema, and the foveal outer retina appears to be substantially degenerated: line of the external limiting membrane (ELM) and line of junction between inner and outer segments of the photoreceptors (IS/OS) show focal defects in the foveal area. RPE retinal pigment epithelium

Discussion

A prominent feature in acute BRVO is intraretinal hemorrhage. However, although some eyes with BRVO hemorrhage within the subretinal or cystoid spaces [8, 9, 11], information on the nature of these or on their clinical relevance is limited [25]. Using OCT, Spaide et al. [8] reported two cases of BRVO with SRH, and Tsujikawa et al. [11] reported other cases that showed hemorrhage within the macular cystoid spaces. However, the association of the hemorrhage with visual function is not reported. In the current study, detailed OCT examination revealed that in acute BRVO hemorrhage like this was not uncommon. Of our 42 patients with BRVO, 19 had hemorrhage in the foveal cystoid space and 18 had it in the subretinal space at the fovea. In addition, initial detection of these were closely correlated with the final VA.

In acute BRVO, intravascular pressure within the affected retinal veins and capillaries is increased, which leads to leakage and hemorrhage from the affected capillaries. Eyes with BRVO often had large foveal cystoid spaces with surrounding small cystoid spaces in the inner nuclear layer and outer plexiform layer, in many cases with SRD at the fovea [10, 11]. In the present study, of 18 eyes with foveal SRH, 16 showed hemorrhage within the foveal cystoid spaces. On OCT sections, hemorrhage within the foveal cystoid spaces was sometimes connected to the underlying SRH through the external boundary of the retina. It is possible that hemorrhage from the affected capillaries accumulates within the foveal cystoid spaces and then flows into the subretinal space through the base of the cystoid space.

In the current study, initial detection of hemorrhage within the subretinal and/or foveal cystoid spaces had no correlation with the initial VA. It is well known that submacular hemorrhage in both age-related macular degeneration [26, 27, 28, 29] and in retinal macroanurysm [27, 30] often causes an immediate decrease in VA. However, even if the hemorrhage associated with BRVO is at the fovea, it does not cause an immediate severe decrease in foveal visual function. In acute BRVO, because the foveal SRH is small and usually exists with some subretinal fluid, it may not block oxygen and nutrients from choroidal circulation and consequently not develop acute impairment of visual function. At the final examinations of the present study, the macular edema was substantially reduced, and both SRD and SRH had been almost entirely absorbed. In parallel with the resolution of the macular edema, some eyes showed recovery in the integrity of foveal photoreceptor layers. The final conditions of the foveal ELM and the IS/OS lines were closely correlated with the final VA. Furthermore, the defect lengths in the ELM and IS/OS lines were most closely correlated with poor VA. Ojima et al. [31] report similar findings in eyes with resolved central serous chorioretinopathy. Eyes with a fine defect of the foveal IS/OS line usually achieved good VA after complete resolution of the SRD, whereas a severe defect of the foveal IS/OS line often resulted in substantial visual impairment.

By simple regression analysis, hemorrhage within the foveal cystoid spaces (r = 0.459, P = 0.002) and foveal SRH (r = 0.361, P = 0.019) at the initial examination showed close correlations with poor final VA. Using multiple regression analysis, final VA showed only a marginal correlation with foveal SRH (ß = 0.160, P = 0.061), and there was no correlation between the final VA and hemorrhage within the foveal cystoid spaces (ß = 0.279, P = 0.302). As mentioned above, because most eyes with foveal SRH also had some hemorrhage within the foveal cystoid spaces, these might be confounding factors. This may be explained by our hypothesis that hemorrhage from the affected retinal capillaries accumulates within the foveal cystoid spaces and subsequently flows into the subretinal space.

Because the multiple regression analysis suggested that foveal SRH is one of the factors that determines visual prognosis in acute BRVO, we separated our patients into two groups by initial detection or no detection of a foveal SRH. Eyes with SRH had a mean longer defect of the foveal IS/OS line and poorer final VA than eyes without SRH. Although foveal SRH was not associated with acute impairment of foveal function, it seemed to cause chronic damage to the overlying foveal photoreceptor layer, which resulted in the limited recovery of vision.

Previous experimental studies suggest several mechanisms by which SRH damages the overlying photoreceptor cells, i.e., clot retraction [32], iron toxicity [33, 34, 35] and blockage of nutrient diffusion from the choroidal circulation [36]. The primary toxic agent released from SRH is thought to be iron as the form of ferritin [37], and increased iron in the photoreceptor outer segments is reported to exert a toxic effect by inducing oxidative stress to outer segment lipids [38]. Another experimental study reports that fibrin made from the SRH interdigitated with photoreceptor outer segments and subsequently tore the inner and outer segment sheets out of photoreceptors. In eyes with BRVO, foveal SRH may chronically damage overlying photoreceptors, leading to a decrease in central visual function even after resolution of the hemorrhage.

Major limitations of the current study are its retrospective nature and small sample size. In addition, the study compared OCT images only between the initial and final examinations. There is also the possibility of effects of the treatment administered to the patients, which may induce a bias in the interpretation of data. Despite these shortcomings, we demonstrated that foveal SRH is not uncommon in BRVO and may cause subsequent damage to the foveal photoreceptor layer, which results in poor visual function after resolution of the retinal edema and retinal hemorrhage. However, prospective studies with larger sample sizes are necessary to avoid treatments effects.

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Copyright information

© Japanese Ophthalmological Society 2013

Authors and Affiliations

  • Yuki Muraoka
    • 1
  • Akitaka Tsujikawa
    • 1
  • Tomoaki Murakami
    • 1
  • Ken Ogino
    • 1
  • Kazuaki Miyamoto
    • 1
  • Nagahisa Yoshimura
    • 1
  1. 1.Department of Ophthalmology and Visual SciencesKyoto University Graduate School of MedicineKyotoJapan

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