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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.

To investigate the outcomes of intravitreal aflibercept and gas injections for submacular hemorrhage (SMH) associated with polypoidal choroidal vasculopathy (PCV).We retrospectively reviewed the medical records of 22 eyes with SMH secondary to PCV that underwent intravitreal aflibercept and 100% perfluoropropane (0.3-0.5 mL) followed by 3-day prone positioning from August 2013 through November 2020. The primary outcome measure was best-corrected visual acuity (BCVA) at 12 months.The average SMH size was 13.0 ± 9.7 (range, 2.0-37.8) disc diameter. The complete, partial, and no displacement of the SMH was observed in 8 (36%) eyes, 9 (41%) eyes, and 5 (23%) eyes, respectively. The BCVA (logarithm of the minimum angle of resolution) continuously improved significantly from 0.81 ± 0.41 (Snellen equivalent, 20/125) at baseline to 0.48 ± 0.44 (20/60), 0.33 ± 0.39 (20/43), and 0.28 ± 0.45 (20/38), at 3, 6, and 12 months, respectively (P = 0.01 for 3 months; P 0.001 for 6 and 12 months). The BCVA improved by 3 or more lines in 14 eyes (64%). Two eyes (9%) developed visually significant vitreous hemorrhage, and 1 (5%) eye developed rhegmatogenous retinal detachment; all were successfully treated with vitrectomy. The better BCVA at 12 months tended to be associated with lower height of the SMH at baseline (RIntravitreal aflibercept and gas injections are effective and relatively safe for SMH associated with PCV, resulting in significant visual improvement.

PurposeThe 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.MethodsThis 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.ResultsTwo 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.ConclusionThis 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.

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

To compare the choroidal neovascularization (CNV) flow patterns and the relationship between perforating vessels (PVs) and CNV in the three different stages of networks in myopic CNV (mCNV) using swept-source optical coherence tomography angiography (SS-OCTA). This retrospective study included 28 eyes with mCNV that was divided into three phases (active, scar, and atrophic) and observed by SS-OCTA. SS-OCTA findings, with special focus on the relationship between the PVs and CNV, were compared among the three phases. Overall, the CNV signal was detected in 31 of the 34 areas of CNV (91%); in the active, scar, and atrophic phases, respectively, CNV signals were detected in eight of eight areas of CNV (100%), 10 of 11 areas of CNV (91%), and 13 of 15 areas of CNV (86%). Two signal patterns were observed in each phase, i.e., dense and loop; in the atrophic phase, seven eyes were unclassifiable. The ratio between the dense and loop patterns did not differ significantly among the phases. In 30 of 34 areas of CNV for which clear images were obtained, the PVs and CNV were connected directly or indirectly in 19 area of CNV, and in five areas of CNV, trunk-like vessels were connected to the PVs within the CNV. The numbers of foveal or parafoveal CNVs accompanied by PVs were significantly (p=0.0048) greater than those of the extrafoveal CNV. OCTA provides detailed observation of mCNV and the relationship between CNV and PVs. Although the CNV signal pattern does not differ depending on the degree of atrophy, there are cases in which only the trunk-like vessels connect to the PVs within the CNV in the atrophic phase without CNV flow signal.

To investigate vascular perfusion and foveal avascular zone area in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) after intravitreal aflibercept therapy in central retinal vein occlusion eyes and their association with best-corrected visual acuity.Thirty-five subjects with central retinal vein occlusion and macular edema were evaluated. After macular edema resolution following intravitreal aflibercept, subjects underwent optical coherence tomography angiography to measure SCP and DCP perfusion and the foveal avascular zone within a 3 × 3-mm area. Correlations between best-corrected visual acuity and optical coherence tomography angiography measurements were examined.After intravitreal aflibercept therapy, mean retinal vascular area was 3.41 ± 0.74 mm in the SCP and 3.25 ± 0.91 mm in the DCP. Foveal avascular zone area was 1.03 ± 1.04 mm in the SCP and 1.78 ± 1.73 mm in the DCP. Improved best-corrected visual acuity was significantly associated with better SCP and DCP perfusion (both P0.001) and with smaller SCP and DCP foveal avascular zone areas (both P0.001). Additionally, SCP and DCP perfusion were negatively correlated with macular edema before treatment (P0.05) and ischemia (determined via pretreatment fluorescein angiography, P0.05), and positively correlated with photoreceptor integrity (P0.001).Patients with better retinal perfusion and less retinal ischemia are associated with better visual outcomes after aflibercept in eyes with central retinal vein occlusion.

PurposeTo investigate the frequency and patient characteristics that influence anatomic response of intravitreal aflibercept in treatment-naïve neovascular age-related macular degeneration (AMD).DesignRetrospective, interventional, consecutive case series.MethodsThree 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.ResultsNineteen (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 non-responders.ConclusionIntravitreal 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.

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 Bruch9s membrane and retinal pigment epithelium.

The endothelial and cell-specific angiopoietin-Tie pathway plays an important regulatory role in angiogenesis. In this study, we investigated the associations of theThis 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 inTwo 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; IThis study revealed

At present, the standard treatment of neovascular age-related macular degeneration (AMD) is the repeated administration of antivascular endothelial growth factor (VEGF) agents. However, we often encounter patients who develop tachyphylaxis for anti-VEGF agents. In this study, we investigated the characteristics of patients who developed tachyphylaxis on repeated intravitreal aflibercept (IVA) injections for neovascular AMD and the frequency of tachyphylaxis. Three hundred thirteen eyes (313 patients) with treatment-naive AMD who achieved resolution soon after starting IVA and were followed up for ≥ 12 months were enrolled in this retrospective, interventional, consecutive case series. The eyes were investigated for tachyphylaxis to aflibercept. Tachyphylaxis was defined as absence of any improvement (more than 100 μm) in or worsening of CRT within 1 month after more than two repeated monthly IVA injections when the exudative change remained. Twenty-eight (8.9%) of the 313 eyes developed tachyphylaxis (occult with no classic, n = 14; polypoidal choroidal vasculopathy, n = 14) at an annual rate of about 3%. The mean number of IVA injections was 10.5 ± 7.8, and the mean interval until tachyphylaxis was 20.9 ± 14.0 months. There was a significant difference in the AMD subtypes between the group with tachyphylaxis and the group without it (p = 0.0029). Occult with no classic type and polypoidal choroidal vasculopathy were the only AMD subtypes in the eyes with tachyphylaxis. In the analysis of the eyes that had occult with no classic or polypoidal choroidal vasculopathy, only intraretinal edema was significantly less common (p = 0.042). A combination of photodynamic therapy and aflibercept was effective in 13 (87%) of 15 eyes with tachyphylaxis, and switching to intravitreal ranibizumab was effective in 5 (56%) of 9 eyes. Tachyphylaxis occurs after repeated IVA injections in a minority of patients with AMD for a long term and is more likely to occur in eyes with lesions beneath the retinal pigment epithelium and no intraretinal edema. Treatment of AMD should be performed keeping this fact in mind, while considering the consecutive treatment.

Purpose To establish geometrically based methods for simulating panretinal laser photocoagulation (PRP) for the photocoagulation index. Methods A formula for calculating the curved surface area of a spherical dome was used for the simulation. If the radius of the dome is c and the height of the dome is h, then the curved surface area (S) of the dome is S = π (c2 + h2). We calculated the area of the whole retina using this formula and the anatomical dimensions of the standard eyeball. To simulate PRP with a 400-μm spot on the retina with 1-spot spacing, we drew 400-μm-diameter circles, separated by 400 μm, on a retinal map. We calculated the ratio of the total retinal photocoagulated area to the whole retina, termed the photocoagulation index, in order to investigate the impact of the extent of the photocoagulated area and the pulse duration on PRP. Results The whole retinal area was 1,092 mm2. The numbers of spots in the scattered and full-scattered PRP were 1,222 and 1,814, respectively. The photocoagulation index was 14.1% and 20.9% for scattered and full-scattered PRP, respectively. These values changed to 14.3% (5.6%) and 21.3% (8.3%), respectively, for PRP with a 100-ms pulse or a 20-ms pulse. Conclusions This method will be useful for investigating the impact of various PRP parameters (duration, spacing, intensity of burns, extent of photocoagulated area, etc.) on the photocoagulation index.

Purpose To characterize wide-field optical coherence tomography angiography (OCTA) features of retinal nonperfusion in eyes with branch retinal vein occlusion (BRVO). Methods Automated scanning of five 12 × 12-mm areas of swept-source OCTA and wide-field fluorescein angiography (FA) images was performed in a consecutive case series of 27 eyes in 27 patients with BRVO in this institutional cross-sectional study. The correlation between the areas of retinal nonperfusion detected by both examinations was assessed. Panoramic images obtained in five 12 × 12-mm OCTA scans in eyes with retinal nonperfusion were binarized or skeletonized, and the associations between vascular parameters such as vascular density (VD) and vascular length (VL) with the wide-field FA characteristics were evaluated. Results The mean area of retinal nonperfusion in the OCTA images was 81.0 ± 66.8 mm2 (range, 0.0-188.8). The mean areas of retinal nonperfusion in FA and the total FA images were, respectively, 84.7 ± 72.5 mm2 (range, 0.0-221.9) and 184.1 ± 167.7 mm2 (range, 0.0-515.0). The mean VD was 27.6 ± 3.5% (range, 19.6-33.7), and the mean VL was 12.4 ± 8.5% (range, 5.4-31.3). Separate regression analyses of the areas of retinal nonperfusion in FA (p = 0.0004, R2 = 0.4627) and the total FA (p = 0.0008, R2 = 0.4214) images showed a significant association with the VL. Conclusions OCTA images based on wide-field technologies can quantitatively evaluate retinal nonperfusion in eyes with BRVO.

Purpose To evaluate the impact of spot size, spacing, pattern, duration and intensity of burns on the photocoagulation index, using a geometric simulation of pan-retinal laser photocoagulation. Methods Simulations of full-scattered pan-retinal laser photocoagulation were performed on a retinal map, using a geometry-based method. Simulations consisted of 300-, 400- or 500-μm diameter equidistant spots on the retina with 1.0-spot width spacing, as well as 400-μm diameter spots on the retina in an equidistant pattern or grid pattern, with 1.0-, 0.75-, 0.50-, 0.25- or 0-spot width spacing. For each simulation, we calculated the ratio of the total photocoagulated retinal area to the whole retina, termed the photocoagulation index. We recalculated the photocoagulation indexes using the expansion ratios of photocoagulated lesions by different duration and intensity of burns from a previous study. Results The photocoagulation indexes of the simulated pan-retinal laser photocoagulation with 300-, 400- and 500-μm diameter spots were 20.8%, 20.6% and 21.0%, respectively. The photocoagulation indexes of the 1.0-, 0.75-, 0.50-, 0.25- and 0-spot width spacing configurations of pan-retinal laser photocoagulation burns for the equidistant pattern were 20.6%, 27.1%, 36.7%, 53.2% and 83.1%, respectively, and those for the grid pattern were 17.9%, 23.5%, 31.8%, 46.1% and 72.0%, respectively. The photocoagulation indexes obtained with the equidistant and grid patterns changed (range, 1.7-84.7% and 1.5-73.4%, respectively) when the duration or burn intensity of the pan-retinal photocoagulation was changed. Conclusion This geometric simulation method could evaluate the impact of a range of conditions on the photocoagulation index.

Purpose: To evaluate the 1-year results of intravitreal aflibercept injections for polypoidal choroidal vasculopathy based on indocyanine green angiography findings. Methods: Twenty-nine eyes with treatment-naive polypoidal choroidal vasculopathy treated with intravitreal aflibercept injections and followed longer than 1 year were retrospectively reviewed. The best-corrected visual acuity, optical coherence tomography findings, and polypoidal lesions in indocyanine green angiography were evaluated. Results: The mean number of injections through 1 year was 3.9 ± 1.9 (range: 1–8). Fourteen eyes (48%) were received no additional injections because of no recurrence of exudative change after the first loading dose. The mean best-corrected visual acuity levels at 6 months and 1 year significantly improved, and the mean central retinal thickness significantly decreased at all observation points from the baseline. At 3 months, the polypoidal lesions completely resolved in 19 (66%) eyes. At 1 year, the complete resolution of polypoidal lesions was seen in 4 of 10 eyes with persistent polypoidal lesions at 3 months. However, polypoidal lesions recurred at 1 year in 5 of 19 eyes (26%) with complete resolution of polypoidal lesions at 3 months. Conclusion: Aflibercept is effective for the eyes with treatment-naive polypoidal choroidal vasculopathy to achieve the resolution of polypoidal lesions. The athors need to carefully observe the eyes after confirming complete resolution of polypoidal lesion because of recurrent polyps seen in one-quarter of the study eyes.

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 −6 were evaluated in replication samples of 205 patients, no SNP was significantly associated with treatment outcomes. Among AMD-susceptibility genes, rs10490924 in ARMS2/HTRA1 was significantly associated with additional treatment requirement in the discovery stage (P = 0.0023), and pooled analysis with the replication stage further confirmed this association (P = 0.0013). ARMS2/HTRA1 polymorphism might be able to predict the frequency of injection after initial ranibizumab treatment.

Purpose To investigate microvascular changes in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in eyes with resolved branch retinal vein occlusion (BRVO) and their association with best-corrected visual acuity (BCVA). Methods Eighty-five eyes (82 consecutive patients) with BRVO after resolution of the macular edema were retrospectively evaluated. All patients underwent optical coherence tomography angiography (OCTA) for assessment of microvascular changes, including capillary telangiectasia, microaneurysm, and disruption of the foveal avascular zone (FAZ). The areas of vascular perfusion and FAZ in the SCP and DCP were quantitatively evaluated. Best-corrected visual acuity was measured on the same day as OCTA examination. The correlation between BCVA and OCTA findings was assessed. Results In eyes with resolved BRVO, the mean vascular perfusion areas in the SCP and DCP within a 3 × 3-mm area were 3.75 ± 0.49 and 3.80 ± 0.55 mm2, respectively. The mean FAZ areas of the SCP and DCP were 0.57 ± 0.36 and 0.76 ± 0.38 mm2, respectively. Better BCVA was significantly associated with a larger vascular perfusion area in the SCP (P < 0.001) and DCP (P < 0.001), and a smaller FAZ area in the SCP (P = 0.025) and DCP (P = 0.017). Stepwise multiple regression analysis revealed that the vascular perfusion area in the DCP was the most important parameter significantly correlated with BCVA (R2 = 0.33, P < 0.001). Conclusions Preservation of the deep retinal vasculature is crucial for better visual function in BRVO.

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.

Purpose We determine the angiopoietin 2 (ANGPT2) gene as a new susceptibility gene for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). Methods A total of 34 haplotype-tagging single-nucleotide polymorphisms (SNPs) were first genotyped in an exploratory Hong Kong Chinese cohort. Suggestive SNPs were replicated in a Shantou Chinese cohort and an Osaka Japanese cohort, with a total of 2343 subjects. The SNP rs800292 in the complement factor H (CFH) gene was genotyped in all the subjects. Genetic association and gene-gene interaction were analyzed. Results In the Hong Kong cohort, four SNPs in ANGPT2 (rs13255574, rs4455855, rs13269021, and rs11775442) were nominally associated with nAMD and PCV. The four ANGPT2 SNPs showed the same trends of association in the Shantou and Osaka cohorts. Combining the data from the 3 study cohorts revealed that SNPs rs4455855 and rs13269021 achieved study-wise significance (P < 0.0016), conferring an approximately 1.3-fold of increased risk for nAMD and PCV. Interaction analysis revealed the CFH SNP rs800292 has a highly significant interaction with the ANGPT2 SNP rs13269021 in nAMD and PCV in the combined analysis. Subsequent stratification analysis confirmed the interaction. Conclusions This study reveals ANGPT2 as a new susceptibility gene for nAMD and PCV, and it may affect disease susceptibility in association with CFH. Thus, this report provides new insights into the genetic architecture of nAMD and PCV.

Purpose To investigate the changes in the retinal microvasculature during the course of anti-VEGF therapy in eyes with macular edema due to retinal vein occlusion (RVO) and their association with visual outcomes. Methods The vessel density (VD) and foveal avascular zone (FAZ) area in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were quantitatively measured by optical coherence tomography angiography (OCTA) in 48 consecutive eyes with RVO before and 1, 3, 6, 9, and 12 months after anti-VEGF therapy. Anti-VEGF therapy was performed either with ranibizumab or aflibercept following a pro re nata (PRN) regimen. The correlation between post-treatment best-corrected visual acuity (BCVA) and changes in the retinal microvasculature evaluated by OCTA were assessed. Results The BCVA improved significantly at 12 months (P < 0.001). Better BCVA at 12 months was significantly associated with a better VD in the SCP and DCP both at baseline (R2 = 0.524, P < 0.001 and R2 = 0.457, P < 0.001, respectively) and at 12 months (R2 = 0.521, P < 0.001 and R2 = 0.662, P < 0.001, respectively). Overall, both VD and FAZ did not change significantly during the 12 months. However, the progression of nonperfusion was observed in the SCP in 6 (13%) eyes and in the DCP in 10 (21%) eyes. The number of macular edema recurrence was significantly associated with a decrease in the VD (P = 0.006 [SCP] and P < 0.001 [DCP]) and less visual gain (P = 0.02) after treatment. Conclusions Anti-VEGF therapy maintains retinal perfusion in most patients with RVO. Preserving retinal perfusion is crucial for better visual outcomes.

PURPOSE The purpose of this study was to investigate the sensitivity of various scan modes of spectral-domain optical coherence tomography (SD-OCT) for detecting pathologies that may accompany myopic foveoschisis, which is important for making surgical decisions and planning surgical strategies for myopic foveoschisis. METHODS Twenty-one eyes of 18 patients were diagnosed with myopic foveoschisis by SD-OCT. Patients were examined with SD-OCT using both a five-line raster scan and a three-dimensional scan at the same visit. The detection rates of pathologies such as macular hole, epiretinal membrane, retinal vascular microfolds, internal limiting membrane detachment, paravascular microhole, and photoreceptor inner and outer segments defect were compared between modes. RESULTS The three-dimensional scanning mode of the SD-OCT tended to be superior to both the one-line and five-line raster scanning modes for detecting inner and outer segments, epiretinal membrane, macular hole, paravascular microhole, and internal limiting membrane. The three-dimensional mode had a significantly higher detection rate (71%) of retinal vascular microfolds than both the 1-line (19%, P < 0.01) and 5-line raster scanning modes (33%, P < 0.05). CONCLUSION The three-dimensional scan mode of SD-OCT was more sensitive for detecting the pathologies that accompany myopic foveoschisis, providing important information for vitreous surgery.

The choroidal circulation in high myopia decreases in conjunction with ocular enlargement experimentally and clinically.1 2 Using indocyanine green angiography (ICGA), investigators have reported narrowing and loss of the large choroidal vessels during the follow-up period.3 4 ICGA is a useful diagnostic tool with which to observe the choroidal circulation, and Heidelberg retina angiography 2 (HRA2; Heidelberg Engineering, Heidelberg, Germany) is a confocal laser scanning system that provides a higher resolution of ICGA compared with the conventional fundus camera. In the current study, we report a new finding of choroidal vasculature seen on HRA2-ICGA. ### Case 1 A 78-year-old woman had myopic choroidal neovascularization (mCNV) in her right eye. The best-corrected visual acuity (BCVA) was 20/40. The axial length was 27.93 mm. Fluorescein angiography (FA) and fundus photography showed subfoveal choroidal neovascularization (CNV) and several patchy atrophies. Early-phase HRA2-ICGA showed a filling delay, and late-phase HRA2-ICGA showed several linear hypofluorescences that corresponded exactly with the choroidal vessels that were perfused in the early. Conventional ICGA did not detect linear hypofluorescence (figs 1A–D, 2). Figure 1 HRA2-indocyanine green angiography (ICGA), conventional ICGA, fluorescein angiography (FA) and fundus photography from case 1. (A) Early-phase HRA2-ICGA showing normal choroidal circulation (arrows) except for a localized filling delay at the macula. An area of …

Purpose To compare retinal thickness (RT) measurements between traditional 6 radial line scans and three-dimensional (3D) scans using spectral-domain optical coherence tomography (SD-OCT). Design Prospective, consecutive case series. Methods Twenty eyes of 17 patients with macular diseases and 8 healthy subjects were scanned using 2 different methods (3D scan and 6 radial line scan) using 2 different SD-OCT devices (Topcon OCT-1000 [Topcon Inc, Paramus, New Jersey, USA] and Canon SPOCT [(Canon/Optopol Inc, Depew, New York, USA]) by an experienced OCT operator. In 16 eyes, the data of TD-OCT were also obtained for comparison. The RT in 9 regions based on Early Treatment Diabetic Retinopathy Study areas were analyzed and compared. Bland-Altman plots were used to evaluate agreement. Results In the eyes with macular diseases, there was no significant difference in the RT between 3D and 6 radial line scans except the center subfield ( P = .011) on the Topcon OCT-1000, and inner inferior ( P = .031) and outer nasal ( P = .014) areas on the Canon SPOCT. In the healthy subjects, there was no significant difference between the different scans on both SD-OCT devices. The 95% limit of subjects was 3.2 to 30.6 μm and 16.7 to 28.3 μm in the eye with macular diseases on OCT-1000 and SPOCT, respectively, and 6.7 to 13.6 μm and 10.8 to 32.3 μm in healthy subjects on OCT-1000 and SPOCT, respectively. Conclusions Preliminary results suggest the RT obtained by the 2 different scan patterns, 3D scan and 6 radial line scan, did not differ significantly on SD-OCT.

Purpose: To report new indocyanine green angiographic (ICGA) findings after intravitreal bevacizumab (IVB) for myopic choroidal neovascularization (mCNV). Cases report: Three eyes of three patients with mCNV were examined with fluorescein angiography (FA) and ICGA using Heidelberg Retinal Angiograph 2 and the conventional fundus camera before and after IVB. The cessation of angiographic leakage on FA was achieved in all eyes (100%) after IVB, however the hypofluorescent line delineating the margin of the neovascular tissue appeared in ICGA seemingly according to the contraction of mCNV. It was not detected either on FA or ICGA with the conventional camera. This hypofluorescence line enlarged over the time. Conclusion: The contraction-associated hypofluorescence line, namely marginal crack line, indicates the early damage of retinal pigment epithelium and seems to lead to expanding macular chorioretinal atrophy typically seen in mCNV.

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. 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. 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. 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.

To clarify the characteristics of choroidal neovascularization (CNV) due to myopic CNV (mCNV) and the relation to lacquer crack (LC) formation.Thirty-seven eyes with mCNV underwent fluorescein angiography (FA) and indocyanine green angiography (ICGA) using Heidelberg Retina Angiograph 2 (HRA2; Heidelberg, Germany). mCNV was detected by FA and ICGA; LCs were detected by late-phase ICGA.Thirty-five eyes (95%) had classic mCNV, and 2 (5%) had occult CNV. LCs developed in 35 (95%) of 37 eyes. In 33 eyes (94%), classic mCNV originated from LCs; the 2 other eyes had small horizontal dotlike LCs, but mCNV originated from the adjacent area of LC. No occult CNV was associated with LCs. Two morphologic types of LCs were observed, linear (21 eyes [62%]) and stellate (12 eyes [32%]) from which mCNV originated, with no significant differences in parameters between the two types. Classic mCNV demonstrated well-delineated hyperfluorescence by late-phase ICGA in 10 eyes (29%), which was significantly correlated with absence of a dark rim (P = 0.022).ICGA using HRA2 provides more detailed information on mCNV and LCs. LC formation is essential for classic mCNV to develop. Morphologic variations of LCs were not different clinically. Late-phase hyperfluorescence, probably due to the absence of pigment epithelium around the mCNV, may represent its activity.

Background/aims: To investigate fundus autofluorescence (FAF) findings in eyes with myopic choroidal neovascularisation (CNV). Methods: Observational case series. Twenty-seven consecutive eyes with CNV for at least 1 year were included. FAF patterns, time after the onset of CNV seen on FAF and FAF changes were evaluated. Results: The following patterns were observed: pattern I (n = 2), relative hypoautofluorescence around the CNV surrounded by hyperautofluorescence a mean of 17 months after CNV onset; pattern II (n = 11), small lobular or multilobular well-defined FAF defects within a relatively hypoautofluorescent region surrounded by hyperautofluorescence a mean of 35 months after onset; pattern III (n = 4), large lobular or multilobular well-defined FAF defects surrounded by hyperautofluorescence a mean of 59 months after onset; and pattern IV (n = 10), large lobular or crescent-shaped well-defined FAF defects a mean of 107 months after onset. Well-defined FAF defects corresponded to chorioretinal atrophy on colour fundus photographs. During the follow-up period, two eyes with pattern I evolved into pattern II. Lobular or multilobular well-defined FAF defects enlarged in 11 eyes (pattern II, nine eyes; pattern III, two eyes). Conclusion: Autofluorescent changes progress over time through pattern grading. A pattern classification might be helpful to predict chorioretinal atrophy changes around myopic CNV.

Retinal pigment epithelial (RPE) cell-mediated extracellular matrix contraction is believed to contribute to developing proliferative vitreoretinopathy. It has been shown that platelet-derived growth factor (PDGF) and its intracellular signaling pathway, including mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K), are mainly involved in this process. The aim of this study is to investigate how these downstream signaling pathways are related to RPE-mediated collagen gel contraction. We performed the gel contraction assay to evaluate the effect of PDGF in cultured ARPE-19 cells under the presence or absence of PD98059, MAPK inhibitor or wortmannin, PI3K inhibitor. Experiments treated with neutralizing antibody for various subtypes of integrin were also performed and the effect on PDGF-induced gel contraction was investigated. Expression changes of integrin alpha1, alpha2 and beta1 after PDGF stimulation was evaluated using quantitative real-time PCR and flow cytometry. The results showed that PDGF up-regulated ARPE-19 cell-mediated gel contractile activity. PDGF-induced collagen gel contraction was attenuated under presence of PD98059, wortmannin, or neutralizing antibody for integrin alpha1, alpha2, or beta1, all of which are critical subset for binding with type I collagen. The expression of integrin alpha1 and alpha2 was increased after PDGF stimulation in both real-time PCR and flow cytometry, however beta1 expression was not increased. PD98059 significantly attenuated integrin alpha1 and alpha2 expressions. However, wortmannin did not have the same effect. In conclusion, PDGF promotes ARPE-19 cell-mediated gel contraction via both MAPK and PI3K. This was probably due to an increased expression of integrin alpha1 and alpha2, which is mediated by MAPK, but not by PI3K. PI3K may regulate collagen gel contraction by another mechanism other than the up-regulation of integrin expression.

Purpose We performed vitrectomy on two eyes for persistent myopic foveoschisis (MF) after primary surgery that did not include internal limiting membrane (ILM) peeling. Design Interventional case reports. Methods Two highly myopic eyes of two patients with persistent MF after primary vitrectomy and gas tamponade but without ILM peeling were treated with pars plana vitrectomy, residual vitreous cortex removal, ILM peeling, and long-term gas tamponade. Results Total foveal reattachment was achieved and best-corrected visual acuity (BCVA) improved in both eyes. Conclusions Reoperation including complete vitreous cortex removal and ILM peeling could be beneficial for patients with persistent MF after primary surgery, indicating that vitreous cortex removal and ILM peeling are critical in treating MF.

PURPOSE We measured postoperative macular hole (MH) size after vitrectomy for MH and retinal detachment (MHRD) in high myopia and investigated potentially associated factors. METHODS Eleven patients (11 eyes) with high myopia (axial length, 25.6-30.8 mm; mean patient age +/- SD, 64.0 +/- 4.31 years) who had retinal attachment without MH closure after vitrectomy for MHRD were included in the study. Postoperative MHs were measured using optical coherence tomography. A horizontal 5.65-mm-long scan of the retina was obtained, and the MH size was measured as the length between the edges of the MH using the retinal thickness mode of the optical coherence tomography system. RESULTS The mean postoperative MH size +/- SD was 1,220 +/- 450 microm. Only axial length was significantly associated with postoperative MH size (P < 0.05). There was a tendency for smaller MH sizes to be associated with better postoperative best-corrected visual acuity (P = 0.06). CONCLUSIONS Persistent MHs after vitrectomy were enlarged according to axial length elongation in highly myopic eyes. Even if MH closure was not successful, the maximum effort to shorten postoperative MH size led to a better postoperative outcome.

Macular holes cause retinal detachments in highly myopic eyes. Because degenerative macular changes often coexist, biomicroscopic evaluation of macular hole status after retinal reattachment is sometimes difficult. We studied macular holes with retinal detachment after vitrectomy using optical coherence tomography and evaluated the anatomic status of the hole and factors associated with anatomic success.Retrospective, nonrandomized, comparative study.Sixteen eyes that underwent vitrectomy for retinal detachment associated with a macular hole were included. Internal limiting membrane peeling with indocyanine green was performed in 14 eyes; the epiretinal membrane was peeled with a diamond-dusted membrane scraper alone in two eyes. All retinas reattached postoperatively. The follow-up period at the optical coherence tomography examination was at least 6 months.Optical coherence tomography was performed vertically and horizontally, and the presence of a persistent macular hole was determined. Other information was obtained from patient records.The macular holes closed in seven of 16 eyes (44%). Age, sex, axial length, preoperative best-corrected visual acuity, duration of symptoms, preoperative refractive error, and the preoperative area of the retinal detachment were not significantly correlated with hole closure. Improved postoperative best-corrected visual acuity (P.05) was significantly associated with macular hole closure, and more frequent visual improvement (P =.06) was of borderline significance.The success rate was lower than those obtained in eyes without myopia or in myopic macular holes without retinal detachments. Macular hole closure may predict improved visual outcome for patients with retinal detachment and macular holes. Optical coherence tomography detects persistent macular holes in highly myopic eyes with retinal detachment.

PURPOSE To report the intraretinal changes seen on the spectral-domain optical coherence tomography after indocyanine green (ICG) assisted internal limiting membrane peeling for macular hole. METHODS A 76-year-old woman with closed macular hole after ICG-assisted internal limiting membrane peeling presented poor visual acuity. Infrared-red, fundus autofluorescence, ICG fluorescence, time-domain OCT and spectral-domain optical coherence tomography images were obtained. RESULTS Spectral-domain optical coherence tomography showed the irregular bumps of the retinal pigment epithelium, thinning of the overlying photoreceptor inner and outer segment layer, and enhanced reflectivity of external limiting membrane layer that corresponded to residual ICG fluorescence dots. The area of retinal pigment epithelium changes and inner and outer segment layer disruption seemed to correspond to residual ICG fluorescence in the previous macular hole bed. CONCLUSION The intraretinal changes were observed in areas of retained ICG after ICG-assisted internal limiting membrane peeling. Spectral-domain optical coherence tomography detected these changes clearly.

To compare the long-term outcomes of simple hemorrhage (SH) without any treatments and myopic choroidal neovascularization (mCNV) treated with intravitreal bevacizumab in highly myopic eyes.Twenty eyes (17 patients) with SH and 28 eyes (27 patients) with mCNV were included. We retrospectively evaluated the refractive error, axial length, age, best-corrected visual acuity, and the integrity of photoreceptor inner segment/outer segment junction and compared the two groups.The mean patient age was 41.6 ± 11.2 years, the mean refractive error -12.7 ± 3.57 diopters, and the mean axial length was 29.64 ± 1.42 mm. Patients in the SH group were significantly (P0.001) younger than those in the mCNV group (34.8 vs. 46.5 years, respectively). There were no significant differences in other parameters between the groups. Compared with baseline, the best-corrected visual acuity improved significantly (P0.01) at 12 months in both groups. The change in vision at 12 months in the SH group was significantly (P0.05) better than that in the mCNV group, although there were no significant differences at 3 months or 6 months. The final integrity of photoreceptor inner segment/outer segment junction was significantly associated with the final best-corrected visual acuity (P0.05).Eyes with SH had a more favorable visual prognosis compared with eyes with mCNV treated with intravitreal bevacizumab. The differential diagnosis of these pathologies is important.

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.

PURPOSE To report the intraretinal microstructure in macular hole and retinal detachment in a highly myopic eye using spectral-domain optical coherence tomography. METHODS Two eyes of two patients with macular holes and retinal detachment were examined with spectral-domain optical coherence tomography. Fundus photographs and time-domain optical coherence tomography images also were obtained. RESULTS Spectral-domain optical coherence tomography disclosed outer retinal fold formation toward the subretinal space at the level of the photoreceptor inner and outer segment layer, the cystoid spaces expanding outside of the macular hole and epiretinal membrane in all eyes. CONCLUSION The outer retinal fold may indicate the tension of the inner retina and the redundancy of the outer retina, which may be responsible for the occurrence of macular holes and retinal detachment in these eyes.

We compared the visibility of retinal and choroidal pathologies using high-penetration optical coherence tomography (HP-OCT) with a long-wavelength light source (1,050 nm) and conventional spectral-domain OCT (SD-OCT) in age-related macular degeneration (AMD). One hundred and forty-six eyes were included: 63 eyes with AMD, 79 eyes with polypoidal choroidal vasculopathy (PCV), and four eyes with retinal angiomatous proliferation. The SD-OCT and HP-OCT images were compared using the grading criteria to grade the visibility of the retinal changes, the line corresponding to the retinal pigment epithelium (RPE), and the chorioscleral interface (CSI). In 132 eyes with a pigment epithelial detachment (PED), we graded the structures inside the PED, Bruch’s line, and the CSI. We compared the visibility of those changes in eyes with subretinal hyperreflective changes due to a subretinal hemorrhage (SRH) (n = 17) or a hemorrhage inside the PED (HPED) (n = 12). HP-OCT provided superior visibility of the following structures compared to SD-OCT (P

Purpose We investigated the association of the ATP-binding cassette, subfamily G, member 1 (ABCG1) gene with polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (nAMD) in independent Chinese and Japanese cohorts. Methods A total of 12 haplotype-tagging single-nucleotide polymorphisms (SNPs) and the SNP rs57137919 in the ABCG1 gene were first analyzed in a Hong Kong Chinese cohort of 235 nAMD, 236 PCV, and 365 controls, using TaqMan genotyping assays. Two SNPs (rs57137919 and rs225396) that showed a disease-association were genotyped in a Shantou Chinese cohort of 189 nAMD, 187 PCV, and 670 controls, and an Osaka Japanese cohort of 192 nAMD, 204 PCV, and 157 controls, totaling 2435 subjects. Association analysis was performed in individual cohorts, followed by a pooled analysis of the data from all three cohorts. Results In the Hong Kong cohort, SNP rs57137919 was associated with PCV (odds ratio [OR] = 1.35). A tagging SNP rs225396 was associated with nAMD (OR = 1.28) and PCV (OR = 1.32). In the Osaka cohort, SNP rs225396 was associated with nAMD (OR = 1.42) and PCV (OR = 1.74). In the pooled analysis involving the 3 study cohorts, rs225396 showed an enhanced association with nAMD (P = 0.01, OR = 1.21, I2 = 14%) and PCV (P = 0.0001, OR = 1.35, I2 = 46%). Conclusions In this study, we have newly identified a haplotype-tagging SNP, rs225396, in ABCG1 to be associated with PCV and nAMD in Chinese and Japanese cohorts. This provides new evidence to support ABCG1 as a susceptibility gene for PCV and nAMD. Further replication in other populations should be warranted.

Background: The change of visual function in Chediak-Higashi syndrome has not been well described. Cases: The visual function of a 12-year-old Japanese girl with ocular albinism due to Chediak-Higashi syndrome was followed by periodic ophthalmological examinations. Observations: A lack of pigmentation in the iris and ocular fundus, and pigmentary degeneration of the peripheral retina were observed. The visual loss and the constriction of visual field progressed with increasing age. The electroretinogram was extinguished at 12 years of age. Conclusions: The constriction of the visual field may be due to the pigmentary degeneration of the ocular fundus. Ophthalmologists should be aware that progressive visual loss and the constriction of visual field can occur in patients with Chediak-Higashi syndrome as they grow older.