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Abstract Intravitreal injection of aflibercept (IVA) has successfully treated polypoidal choroidal vasculopathy (PCV), and polyp morphology is an important indicator of treatment efficacy. However, many studies have not reported the presence or absence of polyp regression and treatment outcomes, and few studies have reported polyp reduction and treatment outcomes in cases with residual polyps. We retrospectively measured the polyp area on indocyanine green angiography images before and after the IVA loading phase and investigated the regression and reduction of polyps and treatment outcomes of 81 eyes with PCV treated with IVA. We investigated the relationship between the presence or absence of complete regression of polyps and the percentage change in the polyp area and treatment outcomes. Eyes with complete polyp regression had significantly better visual acuity improvements compared with baseline at 12 months (P = 0.0108), fewer treatments (P = 0.0024), fewer recurrences during 12-months follow-up (P = 0.0010), and more “dry maculas” at 3 months (P = 0.0048) than eyes in which polyp regression did not occur. A significant correlation was seen only between the percentage of polyp regression and visual acuity at 3 months (P = 0.0395). Regarding IVA therapy for PCV, the presence or absence of complete polyp regression at the end of the loading phase affected the treatment outcome, whereas the degree of polyp reduction in cases of residual polyps had no effect.

Purpose: Myopic choroidal neovascularization (CNV) and myopic traction maculopathy are major complications of pathologic myopia, and myopic foveoschisis (MF) is one of several symptoms that can be included under the general term “myopic traction maculopathy”; however, only a few cases will have MF around the myopic CNV. We report three cases with MF around myopic CNV that followed different clinical courses observed using swept-source optical coherence tomography. Observations: Case 1 was a 69-year-old woman with an axial length of 29.71 mm, myopic CNV, and MF in the left eye. One month after intravitreal injection of ranibizumab (IVR), a macular retinal detachment (RD) expanded. Vitrectomy and gas tamponade were performed during month 2; the macular RD and MF resolved gradually thereafter. Case 2 was a 54-year-old man with an axial length of 30.59 mm, myopic CNV, and MF in the right eye; after IVR, a macular RD developed and gradually expanded until month 4; the RD and MF resolved spontaneously and resolved during month 8. Case 3 was a 66-year-old woman with an axial length of 28.63 mm, myopic CNV, and MF in the left eye. A macular RD expanded 1 month after a previous vitrectomy for MF; after intravitreal injection of aflibercept, the macular RD and MF resolved gradually in month 12. In all cases, the CNV was accompanied by subretinal fluid, and two of the three cases had outer lamellar holes. Conclusion and Importance: The MF around the myopic CNV may lead to exacerbated MF and RD during follow-up, and the subretinal fluid caused by the CNV might facilitate MF progression. Since this condition is rare, further investigation of this entity is needed to determine appropriate management.

Introduction: This study aimed to describe the quantitative features of the microvasculature in the cystic lesions of branch retinal vein occlusion (BRVO). Methods: A total of 43 eyes with BRVO, treated with anti-vascular endothelial growth factor therapy, were analyzed. Using wide-field swept-source optical coherence tomography angiography (OCTA), en face OCT images were obtained by depth-integrated reflectivity of the retina, and vascular density (VD), vascular length (VL), vascular lacunarity, and fractal dimension (FD) were evaluated in a 12 × 12-mm area of retinal nonperfusion. Results: The mean area of affected lesions was 38.7 ± 19.8 mm2, and cystic lesions were 8.5 ± 10.1 mm2. VD, VL, and FD were significantly decreased in the cystic lesions compared to other affected lesions in the same eyes (p = 0.0010, p = 0.0001, and p = 0.0003, respectively) and in all eyes (p = 0.0281, p = 0.0050, and p < 0.0001, respectively). VD in cystic lesions within the vascular arcade (25 eyes) correlated with best-corrected visual acuity on OCTA (r = −0.433, and p = 0.0492). Conclusions: Vascular structure in the cystic lesions was unpreserved compared to the other lesions in BRVO. These findings may help in understanding the pathophysiology of retinal edema in BRVO.

Abstract The META-Analysis of Pathologic Myopia Study group proposed a new classification system for myopic maculopathy (MM) with pathologic myopia (PM) defined as MM equal to/more serious than diffuse atrophy or the presence of plus lesions and myopic choroidal neovascularization (mCNV) defined as CNV in the eye with PM. However, CNV in elderly eyes with high myopia (HM) not meeting the PM definition (high-myopia CNV) are not classified as age-related macular degeneration (nAMD) or mCNV. This retrospective study included 39 eyes with high-myopia CNV, 20 eyes with mCNV, and 20 eyes with AMD. All patients were at least 40 years old. We compared the clinical characteristics and treatment outcomes among three groups. The high-myopia CNV group had significantly more CNV types, shorter axial length and fewer lacquer cracks (P

Abstract Although choriocapillaris flow deficit (CFD) around choroidal neovascularization (CNV) is less associated with CNV activity in myopic eyes, no reports are investigating its size as an indicator of CNV activity. We investigated the relationship between CFD and high myopia-related CNV. In this retrospective, observational study, patients underwent optical coherence tomography angiography (OCTA) with split-spectrum amplitude-decorrelation angiography for diagnosing pathological myopic CNV (mCNV); CFD features around CNV margins were evaluated. Of the 33 eyes (30 patients), 11 (33.3%) had active mCNV, and 22 (66.7%) had inactive CNV. Six eyes (18.2%) were treatment-naïve, while the remainder previously underwent anti-vascular endothelial growth factor therapy. On OCTA, blood flow signals were detected in CNV in the outer retinal layer in 28 (84.8%) eyes, including all active cases (11 cases) and 17 (77.3%) of 22 inactive cases. CNV flow signal size correlated significantly with activity (P

Abstract Background During panretinal photocoagulation (PRP), the outer retina, especially the photoreceptors, are destroyed. During such procedures, the impact of the retinal photocoagulation, which is performed in the same photocoagulated area, may change if it is applied to different locations with different photoreceptor densities. Thus, we aimed to evaluate the influence of photoreceptor density on PRP. Methods We constructed a three-dimensional (3D) average distribution of photoreceptors with 3D computer-aided design (CAD) software using previously derived photoreceptor density data and calculated the number of photoreceptors destroyed by scatter PRP and full-scatter PRP (size 400-μm on the retina, spacing 1.0 spot) using a geometry-based simulation. To investigate the impact of photoreceptor density on PRP, we calculated the ratio of the number of photoreceptors destroyed to the total number of photoreceptors, termed the photoreceptor destruction index. Results In this 3D simulation, the total number of photoreceptors was 96,571,900. The total number of photoreceptors destroyed by scatter PRP and full-scatter PRP were 15,608,200 and 19,120,600, respectively, and the respective photoreceptor destruction indexes were 16.2 and 19.8%, respectively. Conclusions Scatter PRP is expected to have 4/5 of the number of photoreceptors destroyed by full-scatter PRP.

Purpose: To define the role of optociliary shunt vessels (OSVs) in eyes with central retinal vein occlusion (CRVO) using OCT angiography (OCTA) with macular parameters. Design: Retrospective, observational, consecutive case series. Participants: Forty-one eyes in 38 consecutive patients with CRVO were analyzed in this study. Methods: Optic disc and macula were imaged by swept-source OCTA (3 × 3 mm) as well as by high-quality fundus photography. Main Outcome Measures: We compared macular vessel density (VD) and visual acuity between eyes in which OSVs developed and those in which they did not. Furthermore, we measured the diameter of the OSVs and analyzed the correlation with macular VD and visual acuity. Results: Optociliary shunt vessels were found in 25 eyes (61%). Central retinal vein occlusion with OSVs did not show any statistical difference compared with CRVO without OSVs in either macular VD of the total retina (0.31 ± 0.07 and 0.26 ± 0.09, respectively; P = 0.0937) or final best-corrected visual acuity (BCVA) (0.30 ± 0.43 logarithm of the minimum angle of resolution [logMAR] and 0.59 ± 0.54 logMAR, respectively; P = 0.0705). The mean OSV diameter was 71 ± 30 μm in CRVO with OSV. The diameter of the OSVs was correlated positively with superficial VD (r = 0.443; P = 0.027), deep VD (r = 0.494; P = 0.012), and total VD (r = 0.491; P = 0.013). Furthermore, the OSV diameter was also negatively correlated with BCVA (logMAR) at the final visit (r = –0.531; P = 0.006). Conclusions: The results demonstrated that the diameter of the OSVs was associated with macular VD and visual acuity in patients with CRVO. The development of large OSVs on the optic disc may be a good indicator of the maintenance of blood flow in the macula.

Background: During the treatment of age-related macular degeneration with anti-vascular endothelial growth factor (VEGF) drugs, we often see cases with anti-VEGF-resistant refractory subretinal fluid. In this report, we present two cases of anti-VEGF-resistant refractory age-related macular degeneration (AMD) due to the concurrent development of central serous chorioretinopathy (CSCR) in eyes previously well controlled with intravitreal anti-VEGF injections. Case presentation: Two patients underwent intravitreal aflibercept for the treatment of neovascular AMD. Initially, both patients responded well to intravitreal aflibercept, resulting in the complete resolution of the subretinal fluid. However, both patients subsequently developed sudden-onset refractory subretinal fluid that did not respond to repeated intravitreal aflibercept. Fluorescein angiography, indocyanine green angiography, and swept-source optical coherence tomography revealed focal leakage spots, choroidal hyperpermeability, and dilated choroidal vessels, respectively, which were distinct from the pre-existing choroidal neovascularization and suggestive of newly developed CSCR. Laser photocoagulation of the leak spots resulted in the complete resolution of the once-refractory subretinal fluid and the maintenance of vision. Conclusions: Our cases highlight that anti-VEGF-refractory subretinal fluid may occur secondary to concurrent CSCR in patients receiving regular anti-VEGF treatments for AMD. In those patients, treatment for CSCR is effective for controlling subretinal fluid that is unresolved by anti-VEGF treatment.

Abstract We conducted a genome-wide association study (GWAS) on the outcome of anti-VEGF treatment for exudative age-related macular degeneration (AMD) in a prospective cohort. Four hundred and sixty-one treatment-naïve AMD patients were recruited at 13 clinical centers and all patients were treated with 3 monthly injections of ranibizumab followed by pro re nata regimen treatment for one year. Genomic DNA was collected from all patients for a 2-stage GWAS on achieving dry macula after the initial treatment, the requirement for an additional treatment, and visual acuity changes during the 12-month observation period. In addition, we evaluated 9 single-nucleotide polymorphisms (SNPs) in 8 previously reported AMD-related genes for their associations with treatment outcome. The discovery stage with 256 patients evaluated 8,480,849 SNPs, but no SNPs showed genome-wide level significance in association with treatment outcomes. Although SNPs with P-values of

Purpose: To report swept-source optical coherence tomography angiography (SS-OCTA) findings after full-fluence photodynamic therapy (PDT) and aflibercept intravitreal injection (IVA) for age-related macular degeneration (AMD). Methods: Five eyes of five patients with AMD treated with PDT and IVA were include into the study. We retrospectively reviewed the data obtained from the five patients using SS-OCTA before and after treatment. Three eyes had type 1 choroidal neovascularization (CNV) and two eyes had polypoidal choroidal vasculopathy. Results: Before treatment, the CNV signals detected in all cases, decreased in three eyes and were not detected completely in two eyes at 1 months after treatment. The areas indicating CNV increased over time, but they did not increase to the baseline level. No CNV signal was detected in one eye during follow-up. In all cases, the exudation unchanged or resolved without additional IVA; the exudation recurred in two cases. In one eye, the CNV signal and the exudation occurred simultaneously; however, there was no association in another eye. A feeder vessel, from which the CNV signal seemed to originate, was seen in one of the five eyes. Conclusion and Importance: SS-OCTA is useful to monitor the morphology of CNV after PDT and IVA, indicating that the remodeling of the choroidal vasculature occurs gradually after treatment. The presence or absence of the CNV signal might indicate CNV activity. Keywords: Photodynamic therapy, OCTA, oct angiography, Anti-vascular endothelial grow factor therapy, Remodeling

Purpose The endothelial and cell-specific angiopoietin-Tie pathway plays an important regulatory role in angiogenesis. In this study, we investigated the associations of the TIE2 (tyrosine kinase, endothelial, TEK) gene with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), using haplotype-tagging single-nucleotide polymorphisms (SNPs) analysis. Methods This study involved totally 2343 subjects, including a Hong Kong Chinese cohort (214 nAMD patients, 236 PCV patients and 433 control subjects), a Shantou Chinese cohort (189 nAMD patients, 187 PCV patients and 531 control subjects) and an Osaka Japanese cohort (192 nAMD patients, 204 PCV patients and 157 control subjects). Thirty haplotype-tagging SNPs in TIE2 were genotyped in the Hong Kong cohort using TaqMan technology. Two SNPs (rs625767 and rs2273717) showing association in the Hong Kong cohort were genotyped in the Shantou and Osaka cohorts. The SNP-disease association of individual and pooled cohorts were analysed. Results Two SNPs (rs625767 and rs2273717) showed suggestive association with both nAMD and PCV in the Hong Kong cohort. In the meta-analysis involving all the three cohorts, rs625767 showed significant associations with nAMD (p=0.01; OR=0.82, 95% CI 0.70 to 0.96; I2=0%), PCV (p=0.02; OR=0.83, 95% CI 0.71 to 0.97; I2=27%) and pooled nAMD and PCV (p=0.002; OR=0.82, 95% CI 0.72 to 0.93; I2=0%), with low inter-cohort heterogeneities. Conclusion This study revealed TIE2 as a novel susceptibility gene for nAMD and PCV in Japanese and Chinese. Further studies in other populations are warranted to confirm its role. [ABSTRACT FROM AUTHOR]

Purpose To investigate the frequency and patient characteristics that influence anatomic response of intravitreal aflibercept in treatment-naïve neovascular age-related macular degeneration (AMD). Design Retrospective, interventional, consecutive case series. Methods Three hundred and sixty-five eyes of 365 patients with AMD who underwent 3 monthly intravitreal aflibercept treatments with follow-up for at least 12 months were investigated. Treatment response was evaluated as follows. Responders were defined as those with complete resolution of exudation, including intraretinal oedema, subretinal fluid and pigment epithelial detachment, or more than a 100 µm decrease of central retinal thickness at 3 months compared with baseline. Non-responders were defined as patients exhibiting an increase in exudation or a decreased central retinal thickness of less than 100 µm. Results Nineteen (5.2%) of 365 eyes were identified as non-responders. The remaining were responders to intravitreal aflibercept. The non-responders group was significantly associated with choroidal vascular hyperpermeability on indocyanine green angiography and lower frequency of subretinal hyper-reflective materials on optical coherence tomography. The central choroidal thickness at baseline and after 3 monthly injections tended to be thicker in the non-responder group than the responder group, although the differences did not meet statistical significance (p=0.066 and p=0.051, respectively). Additional treatments with either intravitreal ranibizumab or PDT in combination with aflibercept were effective in 15 (79%) of 19 nonresponders. Conclusion Intravitreal aflibercept is effective for treating eye pathology in most naïve AMD cases. However, non-responsiveness may occur in small subgroup of patients with choroidal vascular hyperpermeability. [ABSTRACT FROM AUTHOR]

Aim To describe the choriocapillaris features imaged by optical coherence tomography angiography (OCTA) in eyes with myopic maculopathy. Methods In this retrospective, non-invasive, observational case series, 26 eyes with myopic maculopathy and 12 age-matched healthy eyes underwent fluorescein angiography, indocyanine green angiography (ICGA) (highly myopic eyes only), OCT and OCTA, and the choriocapillaris features seen on OCTA and ICGA were compared. Results In all five (19%) eyes with patchy atrophy of the 26 highly myopic eyes, OCTA showed complete loss of the choriocapillaris and large choroidal vessels in the atrophic area. In nine (35%) eyes with diffuse atrophy in the atrophic area, OCTA showed low-density choriocapillaris in all eyes and medium and large choroidal vessels in seven (78%) eyes. In 23 eyes (88%) with lacquer cracks, OCTA showed partial loss of the choriocapillaris in 22 (96%) eyes in the area of the lacquer cracks. OCTA could not visualise the full length of the lacquer cracks in any eyes compared with ICGA. Conclusions OCTA visualised the choriocapillaris clearly. The choriocapillaris features differed depending to the category of myopic maculopathy. In eyes with lacquer cracks, choriocapillaris rupture might be less advanced than the breaks in Bruch's membrane and retinal pigment epithelium. [ABSTRACT FROM AUTHOR]

Aim To observe the choroidal microstructure in polypoidal choroidal vasculopathy (PCV) using high-penetration optical coherence tomography (HP-OCT) with a long-wavelength light source that visualises tissue beneath the retinal pigment epithelium (RPE) and deep choroid, and to compare the findings with those of indocyanine green angiography (ICGA). Methods In this retrospective, non-invasive, observational case series, 19 eyes (18 patients) with PCV were observed using HP-OCT (swept source, 100 000 A-scans/s, 1060 nm wavelength) and ICGA. The HP-OCT scan protocol was a 3×3-mm or 6×6-mm square containing 256×256 or 512×128 A-scans. The choroidal thickness (CT) was measured using HP-OCT. Results ICGA showed 43 polypoidal lesions in 14 eyes and a vascular network in 17 eyes. HP-OCT showed 41 of the 43 polypoidal lesions visualised by ICGA as RPE rings with inner reflectivity and 15 eyes with a vascular network. Six eyes with RPE rings with inner reflectivity on HP-OCT were not visualised on ICGA images. The choroidal vascular network was dilated in 14 (33%) of 43 polypoidal lesions and 22 (47%) of 47 polypoidal lesions on ICGA and HP-OCT images, respectively. The mean CT at the fovea was 250 μm. The CT at the dilated choroidal vessels beneath the polypoidal lesions was significantly (p = 0.0095) thicker than that of the undilated choroidal vessels beneath the polypoidal lesions. Conclusions HP-OCT can visualise choroidal vascular abnormalities in eyes with PCV and should be useful for understanding the pathogenesis of these abnormalities. [ABSTRACT FROM AUTHOR]

Background Spectral domain optical coherence tomography (SDOCT) allows for higher resolution scans and higher scanning speeds compared to time domain OCT (TDOCT). The purpose of this study is to compare the pathology detection rates of various SDOCT devices to the Stratus TDOCT. Methods Patients with neovascular age-related macular degeneration were imaged on the Stratus and one of four SDOCT devices. The images were then analysed in a masked manner evaluating for the presence of epiretinal membrane (ERM), pigment epithelial detachment (PED) and subretinal fluid (SRF). After determining that low scan density with one of the devices was likely the cause of missed PED and SRF compared to the other SDOCT devices the study was repeated with a higher scan density. Results 60 eyes from 60 patients with neovascular macular degeneration were imaged on each SDOCT device, for a total of 240 eyes from 240 patients imaged on Stratus. There were no instances where pathology was visible on Stratus but was missed on SDOCT. The highest incidence of missed pathology was with SRF, followed by ERM and PED. Conclusions The increased resolution and image quality of SDOCT devices over TDOCT allows for finer discrimination of retinal structures. The increased speed of SDOCT allows for dense coverage of the macula resulting in the ability to see smaller areas of PED and SRF. There was a critical threshold for the distance between B-scans in the three-dimensional cube scan for detection of pathology. [ABSTRACT FROM AUTHOR]

Abstract Background  Fundus autofluorescence (AF) derives from lipofuscin in the retinal pigment epithelium (RPE). Because lipofuscin is a by-product of phagocytosis of photoreceptors by RPE, AF imaging is expected to describe some functional aspect of the retina. In this study we report distribution of AF in patients showing macular edema. Methods  Three eyes with diabetic macular edema (DME) and 11 with retinal vein occlusion (RVO), associated with macular edema (ME) were examined. ME was determined by standard fundus examination, fluorescein angiography (FA) and optical coherence tomography (OCT). AF was recorded using a Heidelberg confocal scanning laser ophthalmoscope (cSLO) with 488 nm laser exciter (488 nm-AF), and a conventional Topcon fundus camera with halogen lamp exciter and 580 nm band-pass filter (580 nm-AF). Color fundus picture, FA image and these two AF images were analyzed by superimposing all images. Results  All subjects presented cystoid macular edema (CME) with petaloid pattern hyperfluorescence in FA. In 488 nm-AF, all eyes (100%) showed macular autofluorescence of a similar shape to that of the CME in FA. In contrast, in 580 nm-AF only one eye (7%) presented this corresponding petaloid-shaped autofluorescence. In all cases, peripheral retinal edemas did not show autofluorescence corresponding to the leakage in FA. Conclusions  In eyes with CME, analogous hyperautofluorescence to the CME was always observed in 488 nm-AF, while it was rarely observed in 580 nm-AF. Moreover, this CME hyperautofluorescence was only seen in the macular area. We hypothesize that autofluorescence from CME may be considered as a “pseudo” or “relative” autofluorescence, due to macular stretching following CME that may result in lateral displacement of macular pigments (MPs) and subsequent reduction of MPs density, as MPs block 488 nm-AF more intensely than 580 nm-AF. Although this phenomenon may not directly indicate change of RPE function, it may be used as a method to assess or track CME non-invasively. [ABSTRACT FROM AUTHOR]

Abstract Purpose  Myopic foveoschisis (MF), a major cause of visual loss in highly myopic patients, shows varied foveal anatomic characteristics. We determined how the foveal status is related to surgical results in MF. Methods  Forty-four eyes underwent vitrectomy for MF, including internal limiting membrane (ILM) peeling and gas tamponade. The eyes were divided into three groups depending on the preoperative foveal anatomy: foveal detachment (FD, n = 17), retinoschisis (RS, n = 16), and macular hole (MH, n = 11). Best-corrected visual acuity (BCVA) and optical coherence tomographic findings preoperatively and 3, 6, and 12 months postoperatively were obtained and compared. Results  BCVA improved two lines or more in 81% of the FD group, 50% of the RS group, and 45% of the MH group 12 months postoperatively. The FD group had significantly improved vision (P P = 0.057) and not significant in the MH group. Visual improvement was significantly better in FD eyes than in RS (P P P P P P Conclusions  Vitrectomy including ILM peeling and gas tamponade is safe and effective for MF. Patients with FD showed the most visual improvement postoperatively and therefore can obtain the most benefit from the surgery. Surgery also benefits RS and MH patients by preserving vision. The foveal status, age, duration of symptoms, and preoperative BCVA are key factors determining postoperative visual outcome in MF. [ABSTRACT FROM AUTHOR]

Abstract Purpose  To report on the clinical features of three cases of polypoidal choroidal vasculopathy (PCV) during long-term follow-up after photodynamic therapy (PDT). Design  Interventional case reports. Methods  Among the participants in the Japanese Age-Related Macular Degeneration Trial (JAT) at our hospital, a PCV was seen in three eyes at baseline on retrospective analysis of indocyanine green angiography (ICGA) using fundus camera. We report the clinical features of these cases during more than 4 years follow-up. Results  The mean number of PDT treatments was 5.7. Improved visual acuity (VA) and cessation of fluorescein leakage was achieved within 18 months in all eyes; however, subretinal hemorrhage and subfoveal fluid recurred due to new or recurrent PCV. The final VA decreased markedly in two eyes. Conclusions  The eyes with PCV, which had been treated successfully with PDT, may have developed new or recurrent PCV during long-term follow-up. Periodical ICGA would be needed to detect abnormal choroidal vascular changes. [ABSTRACT FROM AUTHOR]