Cheolmin Yun

Peripapillary choroidal thickness in patients with early age-related macular degeneration and reticular pseudodrusen

PurposeThe purpose of this study was to investigate peripapillary and macular choroidal thickness (CT) in patients with early age-related macular degeneration (AMD) with or without reticular pseudodrusen (RPD).MethodsWe investigated the medical records of 89 patients (89 eyes) with early AMD. The eyes were grouped into three categories according to the extent of RPD: no RPD, localized RPD, and diffuse RPD. Peripapillary and macular CT were measured with images obtained by spectral domain optical coherence tomography. CT in the peripapillary and macular areas was compared among groups.ResultsBoth RPD groups exhibited an older subject age and a greater female predominance compared to the non-RPD group (P = 0.007 and P = 0.030, respectively). Macular and peripapillary CT were different among the three groups (all, P < 0.001), and both RPD groups showed a thinner choroid in all areas compared to the non-RPD group after adjusting for age and sex (all, P ≤ 0.016). Temporal peripapillary and nasal macular CT at 500 μm and 1500 μm, respectively, from the fovea in eyes with diffuse RPD were significantly thinner than that in eyes with localized RPD (P = 0.008, P = 0.016 and P < 0.001, respectively).ConclusionsIn addition to the macular area, the peripapillary CT, including the area outside the macula, was thinner in eyes with RPD than in those without RPD. Significant differences in the papillomacular choroid were observed based on RPD distribution type, which suggests that variation in CT is based on the extent of RPD.

PERIPAPILLARY CHOROIDAL THICKNESS IN CENTRAL SEROUS CHORIORETINOPATHY: Is Choroid Outside the Macula Also Thick?

Purpose: To investigate peripapillary choroidal thickness (CT) outside the macula in central serous chorioretinopathy (CSC). Methods: We reviewed the medical records of 34 patients with unilaterally symptomatic idiopathic CSC and 34 age-matched controls. Subfoveal and peripapillary CT were measured from images obtained by spectral domain optical coherence tomography. The nasal peripapillary CT of the choroid outside the macula was determined. Results: The subfoveal CT of CSC (369.74 ± 54.17 &mgr;m) and fellow eyes (316.18 ± 54.68 &mgr;m) of the patient group were thicker than those of the normal controls (281.90 ± 40.97 &mgr;m, all P < 0.05). The subfoveal CT in CSC was significantly thicker than those in the fellow eyes. Nasal CT was also thicker in CSC (217.59 ± 62.03 &mgr;m) and fellow eyes (206.66 ± 59.35 &mgr;m) of the patient group compared with the normal controls (179.52 ± 39.64 &mgr;m, all P < 0.05). However, there was no difference in nasal CT between CSC and fellow eyes (P = 0.150). Conclusion: This result may suggest that manifest CSC occurs in patients with thick choroids both within and outside the macula, especially when subfoveal CT is increased.

The correlation between retinal sensitivity assessed by microperimetry and contrast sensitivity in diabetic macular oedema

Aim To investigate the relationship between contrast sensitivity (CS) and retinal sensitivity (RS) assessed by microperimetry (MP) in diabetic retinopathy (DR) with clinically significant macular oedema (CSME). Methods A retrospective study was performed with 35 eyes of 35 patients with DR and CSME. Retinal thickness (RT) and MP were tested with the spectral SD-optical coherence topography/scanning laser ophthalmoscope system. Mean central RT at the fovea centres 1 mm zone (CRT) and at the fixation centres 1 mm zone (FCRT) was measured. RS was tested at the fixation centre, within 2° and 4° areas. CS was measured with six target sizes (6.3°, 4.0°, 2.5°, 1.6°, 1.0°, 0.64°) with a contrast glare tester. Results The mean CRT and FCRT were 344.3±136.2 and 359.9±135.5 μm, respectively. Mean log CSs (−log10) with the six target sizes ranged from 0.19 to 1.32. The mean RS at the fixation centre, within 2°, and within 4° area were 8.51±4.81 dB, 8.58±3.88 dB and 9.22±3.56 dB, respectively. RS at all tested areas were significantly correlated to log CS with all target sizes (range, r=0.366–0.755; p=0.0001–0.030). CRT and FCRT were not significantly correlated to log CS or RS. Conclusions CS and RS showed moderately significant correlations in CSME. However, neither CS nor RS was correlated with RT in patients with CSME. It could be that CS and MP are complementary to each other and are useful tools in the evaluation of functional vision.

Ocular perfusion pressure and choroidal thickness in early age-related macular degeneration patients with reticular pseudodrusen

Purpose The purpose of this study was to investigate the relationship between the ocular perfusion pressure (OPP) and subfoveal choroidal thickness (CT) in eyes with early age-related macular degeneration (AMD) with or without reticular pseudodrusen (RPD). Methods We evaluated the clinical history, blood pressure parameters, fundus photography, and optical coherence tomography images of consecutive patients with early AMD. We calculated the mean OPP from blood pressure and intraocular pressure. Results We included 103 eyes from 103 patients, classifying 45 as the RPD group and 58 as the non-RPD group. The mean OPP of the RPD group (46.1 ± 6.5 mm Hg) did not differ from that of the non-RPD group (45.1 ± 5.1 mm Hg, P = 0.325), but the RPD group showed a thinner mean subfoveal CT (158.3 ± 73.0 μm) than the non-RPD group (220.9 ± 67.0 μm, P < 0.001). Among 64 patients who underwent follow-up examination, the rate of change in subfoveal CT in the RPD group (-4.74 ± 0.86 μm/y) was greater than that in the non-RPD group (-2.46 ± 0.75 μm/y, P = 0.028). In the RPD group, a history of systemic hypertension and lower baseline OPP were associated with a higher rate of change in subfoveal CT (P = 0.019 and P = 0.010, respectively). Conclusions Subfoveal CT was thinner in early AMD patients with RPD than in those without RPD. Lower baseline mean OPP and a history of systemic hypertension could be risk factors associated with the progression of choroidal thinning in early AMD patients with RPD.

Morphologic characteristics of chronic macular hole on optical coherence tomography.

Purpose: To investigate the morphologic characteristics of chronic macular holes (MHs) using optical coherence tomography. Methods: We retrospectively reviewed optical coherence tomographic images of consecutive patients who had been diagnosed with MH. Chronic MH was defined as MH that was observed without being surgically treated for at least 1 year. Optical coherence tomographic parameters were compared between chronic and acute MH. Results: Thirteen eyes of 13 patients were classified as chronic MH, and 67 eyes of 67 patients were classified as controls. While the basal hole diameter of chronic MH was not different from that of controls (P = 0.146), the minimum hole diameter (781.8 &mgr;m) of chronic MH was larger than that of controls (448.4 &mgr;m; P < 0.001). The hole height and MH index were smaller in the chronic MH group (380.6 &mgr;m; 0.31) than in control group (469.9 &mgr;m, 0.53; P = 0.033, P = 0.003). Intraretinal fluid was less frequently observed in chronic MH than in controls (P < 0.001). Retinal pigment epithelial atrophy was only observed in chronic MH. Conclusion: Chronic MH has features distinct from those of acute symptomatic MH on optical coherence tomography. These findings provide useful insight for the differentiation of chronic MH from acute MH.

THE EFFECT OF PHOTOPIGMENT BLEACHING ON FUNDUS AUTOFLUORESCENCE IN ACUTE CENTRAL SEROUS CHORIORETINOPATHY.

Purpose: To evaluate the effect of photobleaching on fundus autofluorescence (FAF) images in acute central serous chorioretinopathy. Methods: We obtained prephotobleaching and postphotobleaching images using an Optomap 200Tx, and photobleaching was induced with a Heidelberg Retina Angiograph 2. Degrees of photobleaching were assessed as grayscale values in Optomap images. Concordances among the three kinds of images were analyzed. Hyper-AF lesions in prephotobleaching images were classified as Type 1 (changed to normal-AF after photobleaching) and Type 2 (unchanged after photobleaching). The FAF composite patterns of central serous chorioretinopathy lesions were classified as diffuse or mottled. Initial and final best-corrected visual acuity, central retinal thickness, and disease duration were compared according to fovea FAF type. Results: Forty-one eyes of 41 patients were analyzed. The lesion brightness of postphotobleaching Optomap FAF showed greater concordance with Heidelberg Retina Angiograph 2 FAF (94.74%) than the prephotobleaching Optomap FAF (80.49%). Eyes with Type 1 fovea had greater initial and final best-corrected visual acuity (20/23 vs. 20/41, 20/21 vs. 20/32, P < 0.0001, P = 0.001, respectively) and shorter disease duration (19.68 ± 12.98 vs. 51.55 ± 44.98 days, P = 0.043) than those with Type 2 fovea. However, eyes with diffuse Type 2 fovea had only lower initial and final best-corrected visual acuity (20/23 vs. 20/45, 20/21 vs. 20/36, P < 0.0001, P < 0.0001, respectively) than those with Type 1 fovea. Conclusion: Understanding the photobleaching effect is necessary for the accurate interpretation of FAF images. Furthermore, comparing prephotobleaching and postphotobleaching FAF images may be helpful for estimation of lesion status in central serous chorioretinopathy.

Subconjunctival hemorrhage after intravitreal injection of anti-vascular endothelial growth factor.

PurposeTo investigate the risk factors for subconjunctival hemorrhage (SCH) after intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) and evaluate the relationship between hemodynamic status at the time of injection and SCH.MethodsWe retrospectively reviewed the medical records of 598 cases of 173 patients who underwent intravitreal injection of ranibizumab whose hemodynamic status was monitored at the time of the injection. Cases with SCH after the injection were included in the SCH group. We compared systemic factors, including the hemodynamic status between the SCH group and the control group.ResultsThe SCH group included 67 cases and the control group included 531 cases without SCH. Baseline hemodynamic status was not significantly related to development of SCH. However, systolic blood pressure (BP) at injection was a significant risk factors for SCH (P = 0.034). Elevated systolic BP, mean arterial pressure (MAP), and pulse rate from baseline to time of injection were significantly related to the development of SCH (P = 0.011, P = 0.014, P = 0.036, respectively). In multivariate analysis, hypertension, a large change in MAP, and a fewer previous injections were significant risk factors for SCH after intravitreal injection (P = 0.030, P = 0.032, P = 0.028, respectively).ConclusionsHemodynamic risk factors exist for SCH after intravitreal injection of anti-VEGF. To reduce the risk of SCH, strategies should seek to decrease patient anxiety, especially in those with hypertension.

Generation of Retinal Progenitor Cells from Human Induced Pluripotent Stem Cell-Derived Spherical Neural Mass

Spherical neural mass (SNM) is a mass of neural precursors that have been used to generate neuronal cells with advantages of long-term passaging capability with high yield, easy storage, and thawing. In this study, we differentiated neural retinal progenitor cells (RPCs) from human induced pluripotent stem cells (hiPSC)-derived SNMs. RPCs were differentiated from SNMs with a noggin/fibroblast growth factor-basic/Dickkopf-1/Insulin-like growth factor-1/fibroblast growth factor-9 protocol for three weeks. Human RPCs expressed eye field markers (Paired box 6) and early neural retinal markers (Ceh-10 homeodomain containing homolog), but did not photoreceptor marker (Opsin 1 short-wave-sensitive). Reverse transcription polymerase chain reaction revealed that early neural retinal markers (Mammalian achaete-scute complex homolog 1, mouse atonal homolog 5, neurogenic differentiation 1) and retinal fate markers (brain-specific homeobox/POU domain transcription factor 3B and recoverin) were upregulated, while the marker of retinal pigment epithelium (microphthalmia-associated transcription factor) only showed slight upregulation. Human RPCs were transplanted into mouse (adult 8 weeks old C57BL/6) retina. Cells transplanted into the mouse retina matured and expressed markers of mature retinal cells (Opsin 1 short-wave-sensitive) and human nuclei on immunohistochemistry three months after transplantation. Development of RPCs using SNMs may offer a fast and useful method for neural retinal cell differentiation.

Macular hole closure following anti-vascular endothelial growth factor injection in an eye with myopic choroidal neovascularization

Dear Editor, I am Cheolmin Yun, from the Department of Ophthalmology, Korea University College of Medicine. I write to present a case report of a female patient with a myopic patient suffering from atrophic choroidal neovascularization (CNV) and a full thickness macular hole (FTMH), who was treated with an intravitreal anti-vascular endothelial growth factor (VEGF) injection without vitrectomy. A FTMH in an eye with high myopia has been suggested to have a poorer anatomical and visual prognosis than in an eye without high myopia [1]. FTMHs were reported in 6.26% of highly myopic eyes, but cases with a CNV and a FTMH in the same eye were not common[2]. Shimada [3] presented cases with a FTMH associated with chorioretinal atrophy adjacent to myopic CNV. They suggested that eyes at the atrophic stage of myopic CNV have a higher risk of developing a FTMH, and recommended periodic optical coherence tomography (OCT) examinations for a FTMH. However, the best therapy for these patients has not been determined. A 68-year-old female presented with a ten-day history of decreased visual acuity OD. Her vision was 1.52 logMAR OD. The anterior segment was normal. The axial length of right eye was 28.71 mm. Fundoscopic examination of the right eye showed a subretinal hemorrhage. Fluorescein angiography (FA) indicated a type 2 CNV located close to the fovea with leakage (Figure 1). The patient underwent spectral-domain optical coherence tomography (SD-OCT, 3D OCT-1000 Mark II, Topcon Corp., Tokyo, Japan) examination using three-dimensional scanning protocols with 128 B-scans (512 A-scans per B-scan with a length of 6 mm). The SD-OCT revealed vitreomacular adhesion (Figure 2), and the patient was diagnosed with myopic CNV. Photodynamic therapy (PDT) was performed with verteporfin (Visudyne; Novartis AG, B俟lach, Switzerland). On the SD-OCT scan obtained ten months after the treatment for CNV, retinoschisis and macular detachment were noted adjacent to the previous CNV lesion. She had no visual symptoms and her vision was 1.52 logMAR. Seventeen months after PDT, the patient presented with visual dimness. Her vision was decreased to 2.00 logMAR. SD-OCT demonstrated a FTMH at the location of the previous macular detachment. However, FA did not show apparent leakage from the CNV. Pars plana vitrectomy was recommended. However, the patient refused the surgery. Three weeks after initial diagnosis of the FTMH, a SD-OCT scan revealed that the FTMH had not resolved. After obtaining informed consent, she underwent intravitreal injection of bevacizumab (Avastin; Genentech, South San Francisco, CA, USA). Five days after the intravitreal injection of bevacizumab, closing of the FTMH was observed on SD-OCT examination. SD-OCT images obtained six weeks after the intravitreal injection showed that the macular edema and subretinal fluid were further decreased. Vitreomacular adhesion, which had been observed on SD-OCT before the anti-VEGF injection, was unchanged after closure of the FTMH. FA did not show any change in the CNV. SD-OCT images obtained three months after the intravitreal injection showed that the macular edema and subretinal fluid were further decreased. The patients vision recovered to 1.70 logMAR. The macular hole remained closed until twenty months after the intravitreal injection. In our case, the FTMH eventually developed adjacent to the atrophic CNV that had been treated with PDT. Shrinkage and regression of CNV at the atrophic stage were suggested to induce a FTMH by centrifugal and tangential stretching of the extremely thin atrophic retina at the edge of the CNV [3]. The traction force must be one of the reasons for the Macular hole closure following anti-VEGF injection

Response to the letter to the editor: Comparison of intravitreal aflibercept and ranibizumab injections on subfoveal and peripapillary choroidal thickness in eyes with neovascular age-related macular degeneration

Dear Editor, We appreciate the comments by Uzun et al. concerning our article, in which we investigated the changes in choroidal thickness (CT) after administration of ranibizumab and aflibercept [1]. Uzun et al. highlighted the various factors which might affect CT including age, refractive errors, axial length, and other various systemic factors [2–4]. We agree with this comment; however, because the study design was retrospective, information about all of the related factors was not available. In this study, the refractive error of the ranibizumab group (spherical equivalent, 1.01 ± 1.51 diopters) was not significantly different from that of the aflibercept group (spherical equivalent, 0.45 ± 1.40 diopters, P = 0.233). Systemic factors, hypertension, and diabetes did not differ between the two groups. Because the two groups were treated during a certain period and classified according to the treatment time, there is no definite evidence that other factors need to be investigated. In addition, because this study observed short-term changes, the effect of systemic factors on the choroidal thickness might not be significant. We also agree that we should consider diurnal variations of choroidal thickness, but due to the study’s retrospective design, we could not adjust diurnal variations andmentioned this issue in the limitation section of the manuscript. However, because the retinal clinic in our hospital is only open in the morning, all patients were examined with optical coherence tomography before noon. Because of the timing of the exams, the diurnal variation in the choroidal thickness might not be significant in this study.