Clinical utility of swept-source optical coherence tomography angiography for the diagnosis of exudative maculopathy.

PURPOSE: To assess the feasibility of swept-source optical coherence tomography angiography (SS-OCTA) to differentiate macular diseases, including nonpolypoidal macular neovascularization (MNV), polypoidal choroidal vasculopathy (PCV), type 3 MNV, and chronic central serous chorioretinopathy (CSC) without indocyanine green angiography (ICGA). STUDY DESIGN: Retrospective observational study. METHODS: This study examined 63 eyes of 63 patients with treatment-naive neovascular age-related macular degeneration (AMD), including 23 eyes with nonpolypoidal MNV, 17 eyes with PCV, and 1 eye with type 3 MNV and 22 eyes with chronic CSC. Two independent retina specialists, blinded to the clinical diagnosis, assessed each case of neovascular AMD and chronic CSC using only B-scan and en face images of SS-OCTA without referring to other examination outcomes. RESULTS: By SS-OCTA alone, 19 eyes were diagnosed with nonpolypoidal MNV, 17 eyes with PCV, 2 eyes with type 3 MNV, and 22 eyes with chronic CSC, indicating high sensitivity (82.6%, 94.1%, 100%, and 100%, respectively) and specificity (100%, 97.8%, 98.4%, and 100%, respectively); however, three eyes could not be diagnosed because of obscure images. The agreement of diagnosis with SS-OCTA alone was high between the two specialists (κ = 0.82). CONCLUSION: SS-OCTA showed high sensitivity and specificity in the differentiation of nonpolypoidal MNV, PCV, type 3 MNV, and chronic CSC. The differential criteria based on SS-OCTA could be a substitute for the ICGA-based diagnoses.

Six-Year Outcomes in Subjects with Polypoidal Choroidal Vasculopathy in the EVEREST II Study.

INTRODUCTION: The EVEREST II study previously reported that intravitreally administered ranibizumab (IVR) combined with photodynamic therapy (PDT) achieved superior visual gain and polypoidal lesion closure compared to IVR alone in patients with polypoidal choroidal vasculopathy (PCV). This follow-up study reports the long-term outcomes 6 years after initiation of the EVEREST II study. METHODS: This is a non-interventional cohort study of 90 patients with PCV from 16 international trial sites who originally completed the EVEREST II study. The long-term outcomes were assessed during a recall visit at about 6 years from commencement of EVEREST II. RESULTS: The monotherapy and combination groups contained 41 and 49 participants, respectively. The change in best-corrected visual acuity (BCVA) from baseline to year 6 was not different between the monotherapy and combination groups; - 7.4 ± 23.0 versus - 6.1 ± 22.4 letters, respectively. The combination group had greater central subfield thickness (CST) reduction compared to the monotherapy group at year 6 (- 179.9 vs - 74.2 µm, p = 0.011). Fewer eyes had subretinal fluid (SRF)/intraretinal fluid (IRF) in the combination versus monotherapy group at year 6 (35.4% vs 57.5%, p = 0.032). Factors associated with BCVA at year 6 include BCVA (year 2), CST (year 2), presence of SRF/IRF at year 2, and number of anti-VEGF treatments (years 2-6). Factors associated with presence of SRF/IRF at year 6 include combination arm (OR 0.45, p = 0.033), BCVA (year 2) (OR 1.53, p = 0.046), and presence of SRF/IRF (year 2) (OR 2.59, p = 0.042). CONCLUSION: At 6 years following the EVEREST II study, one-third of participants still maintained good vision. As most participants continued to require treatment after exiting the initial trial, ongoing monitoring and re-treatment regardless of polypoidal lesion status are necessary in PCV. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01846273.

Assessment of factors affecting flicker ERGs recorded with RETeval from data obtained from health checkup screening.

PURPOSE: To determine the factors significantly associated with the amplitudes and implicit times of the flicker electroretinograms (ERGs) recorded with the RETeval system by analyzing the comprehensive data obtained during a health checkup screening. METHODS: Flicker ERGs were recorded with the RETeval system from 373 individuals who had a normal fundus and optical coherence tomography images. The sex, age, anthropometric, ophthalmologic, and hematologic data were collected from all participants who were 40- to 89-years-of-age. Univariable and multivariable linear mixed effects regression analyses were performed to identify factors that were significantly associated with the implicit times and amplitudes of the RETeval flicker ERGs. RESULTS: Univariable linear mixed effects regression analysis showed significant correlations between the implicit times and the best-corrected visual acuity, the age, the axial length, the blood sugar level, and the blood urea nitrogen level. Analyses by multivariable linear mixed effects regression identified that the axial length (ß = 0.28), the age (ß = 0.24), and the blood sugar level (ß = 0.092) were three independent factors that were significantly correlated with the implicit times of the RETeval flicker ERGs. Univariable linear mixed effects regression analysis also showed significant correlations between the amplitudes of the RETeval flicker ERGs and the age, the platelet count, and the creatinine level. Multivariable linear mixed effects regression models identified the age (ß = -0.092), the platelet count (ß = 0.099), and the creatinine level (ß = -0.12) as three independent factors that were significantly correlated with the amplitudes of the RETeval flicker ERGs. However, the smoking habits, body mass index, and the blood pressure were not significantly correlated with either the implicit times or amplitudes of the RETeval flicker ERGs. CONCLUSIONS: Our results indicate that the age and some ophthalmologic and hematologic findings but not the anthropometric findings were significantly associated with the implicit times and amplitudes of the RETeval flicker ERGs. Thus, clinicians should remember these factors when analyzing the RETeval flicker ERGs.

LONG-TERM MORPHOLOGIC CHANGES IN MACULAR NEOVASCULARIZATION UNDER AFLIBERCEPT TREATMENT WITH A TREAT-AND-EXTEND REGIMEN.

PURPOSE: To examine the morphologic changes in macular neovascularization (MNV) secondary to age-related macular degeneration after 2 years of aflibercept treatment under a treat-and-extend (T&E) regimen. METHODS: This retrospective study analyzed the medical records for 26 eyes of 25 patients diagnosed with treatment-naive neovascular age-related macular degeneration and treated with aflibercept under a treat-and-extend regimen for 2 years. The areas of the MNV and vascular structures were assessed using swept-source optical coherence tomography angiography at baseline and after 2 years of treatment. RESULTS: The mean MNV area increased significantly from 0.65 ± 0.42 mm 2 at baseline to 0.78 ± 0.45 mm 2 at 2 years. At 2 years, the mean change in the MNV area from baseline was 22% (interquartile range: 4%-60%). The baseline MNV area was negatively correlated with the change ratio of the MNV areas at 2 years and baseline ( R = -0.68, P < 0.001). Nine of the 26 eyes (34.6%) showed newly formed mature vessels, and 7 eyes (26.9%) showed prominently developing preexisting mature vessels. CONCLUSION: Macular neovascularization expanded and showed vascular maturation under aflibercept treatment with a treat-and-extend regimen. The smaller the MNV at baseline, the greater is its expansion in 2 years.

SPONTANEOUS CLOSURE OF MACULAR HOLE AFTER VITRECTOMY FOR MYOPIC RETINOSCHISIS WITH FOVEAL DETACHMENT.

PURPOSE: To discuss a case of a macular hole formation after vitrectomy for myopic retinoschisis with foveal detachment and spontaneous closure, during long-term follow-up. METHODS: Case report. RESULTS: A 71-year-old man with myopic retinoschisis with foveal detachment had a vitrectomy with internal limiting membrane peeling combined with cataract surgery in the left eye. The preoperative best-corrected visual acuity was 8/20, and the axial length was 27.11 mm. A macular hole with foveal detachment was observed 1 month after surgery. However, the macular hole closed spontaneously with foveal detachment at 4 months of follow-up. Foveal detachment resolved, and the best-corrected visual acuity improved to 20/20 at nine months of follow-up. CONCLUSION: This case suggests that the macular hole formed after vitrectomy for myopic retinoschisis with foveal detachment with internal limiting membrane peeling can close spontaneously.

Displacement of the retina and changes in the foveal avascular zone area after internal limiting membrane peeling for epiretinal membrane.

PURPOSE: We investigated the differences in displacement of the outer and inner macular retina toward the optic disc after vitrectomy with internal limiting membrane (ILM) peeling for epiretinal membrane (ERM). Foveal avascular zone (FAZ) area changes were also investigated. STUDY DESIGN: Retrospective observational study METHODS: This retrospective observational case series included 45 eyes of 43 patients that underwent vitrectomy with ERM and ILM peeling for ERM and 38 normal eyes. The locations of the centroid of the FAZ (C-FAZ, center of the foveal inner retina) and foveal bulge (center of the foveal outer retina) were determined using 3×3mm superficial optical coherence tomography angiography. C-FAZ and foveal bulge displacements, and the pre- and postoperative FAZ areas and their associated factors, were investigated. RESULTS: Postoperative C-FAZ dislocated significantly more toward the optic disc than in pre-operative or normal eyes (P<0.001). C-FAZ and foveal bulge displaced toward the optic disc after surgery; C-FAZ showed significantly greater displacement than foveal bulge (P<0.001). The pre- and postoperative FAZ areas were correlated (P=0.01). Preoperative FAZ areas ≧0.10mm2 were reduced after surgery, and FAZ areas < 0.10mm2 were increased, independent of foveal displacement. CONCLUSION: ILM peeling during vitrectomy for ERM caused larger displacement of the inner and smaller displacement of the outer retinas, towards the optic disc. Postoperative changes in the FAZ area were dependent on the baseline FAZ area, but not on the foveal displacement. ILM may physiologically exert centrifugal tractional forces on the fovea.

Choroidal hemodynamics in central serous chorioretinopathy after half-dose photodynamic therapy and the effects of smoking.

This retrospective study aimed to evaluate choroidal hemodynamics after half-dose photodynamic therapy (PDT) for central serous chorioretinopathy (CSC) and the effects of smoking using laser speckle flowgraphy. This study included 29 eyes of 29 patients treated with half-dose PDT for CSC, who were followed-up for at least 6 months. The mean blur rate (MBR) in the PDT irradiation area (whole area), the pachyvessel (PV) area, non-PV (NPV) area, and filling delay (FD) area were assessed at baseline and 1, 3, and 6 months post-PDT, respectively. The MBR was also assessed by smoking status. The MBR significantly decreased from baseline in the whole, PV, NPV, and FD areas at all time points (P < 0.001). Of the 29 patients, 6 were never smokers, 13 were past smokers, and 10 were current smokers. At baseline, no significant difference was found in the MBR in the whole, PV, NPV, and FD areas among never, past, and current smokers. The MBR changes showed a significantly smaller decrease in current smokers than in never smokers in the whole (P = 0.021), PV (P = 0.009), and NPV (P = 0.034) areas, but not in the FD area (P = 0.172). Half-dose PDT for CSC reduced choroidal blood flow in the PDT-irradiated area, which was blunted by current smoking status.

Direct Observation of Retinal Microvessels in Cancer Patients After Systemic Administration of Bevacizumab and Oxaliplatin.

BACKGROUND/AIM: Antiangiogenic chemotherapy is the backbone of the various anticancer therapies. To date no practical biomarker predicting their antitumor effects and toxicity has been reported. We aimed to determine the feasibility of direct retinal observation as a practical biomarker in antiangiogenic chemotherapy. PATIENTS AND METHODS: By direct retinal observation using a nonmydriatic retinal camera, we measured retinal microvessel diameters in 10 patients with colorectal cancer before and after intravenous infusion of bevacizumab and oxaliplatin. All patients also received oral capecitabine during their therapy. RESULTS: Retinal microvessel diameters were decreased from baseline temporarily by 14.5±6.5% after infusion of bevacizumab and oxaliplatin in five patients who responded to treatment and 8.8±6.2% in the other five patients (p=0.008). CONCLUSION: Measurement of retinal microvessel diameters by direct observation appears to be feasible in patients receiving systemic chemotherapy. The decrease of retinal microvessel diameters might indicate improved tumor response to treatment with bevacizumab-containing systemic chemotherapy.

Switching from aflibercept to brolucizumab for the treatment of refractory neovascular age-related macular degeneration.

PURPOSE: To examine the 16-week outcomes of switching to brolucizumab in eyes with neovascular age-related macular degeneration (nAMD) refractory to aflibercept. STUDY DESIGN: Retrospective observational study. METHODS: Data of eyes with nAMD who switched to brolucizumab because of resistance to aflibercept were collected. The best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative status on optical coherence tomography were analyzed. RESULTS: A total of 48 eyes of 48 patients were reviewed. At 4 to 7 weeks after switching, BCVA changed from 0.26 ± 0.19 to 0.25 ± 0.21 (not significant; P = 0.95), but CRT significantly decreased from 298.9 ± 108.4 µm to 241.9 ± 92.5 µm (P < 0.001) and CCT from 182.6 ± 89.3 µm to 169.7 ± 82.6 µm (P < 0.001). Of the 23 eyes refractory to monthly aflibercept injections, 12 (52.2%) achieved a dry macula, and 8 (34.8%) reduced exudative changes at 1 month. At 16 weeks, 31 eyes (64.6%) achieved the treatment interval ≥ 8 weeks. Two patients (4.2%) dropped out, 7 eyes (14.6%) developed intraocular inflammation (IOI), and 8 eyes (16.7%) switched back to aflibercept because of the failure to extend the treatment interval ≥ 8 weeks. CONCLUSION: Switching to brolucizumab in eyes refractory to aflibercept conferred favorable outcomes in controlling exudative changes. However, IOI and the regulation of the treatment interval to at least 8 weeks during the maintenance phase disrupted the continuation of brolucizumab treatment.

Prevalence of and factors associated with dilated choroidal vessels beneath the retinal pigment epithelium among the Japanese.

Pachyvessels are pathologically dilated large choroidal vessels and are associated with the pathogenesis of several pachychoroid-related disorders, including central serous chorioretinopathy. We aimed to investigate the prevalence of and risk factors for pachyvessels in the Japanese population. We included 316 participants (aged ≥ 40 years) with normal right eyes. The presence of pachyvessels (vertical diameter > 300 µm, distance to the retinal pigment epithelium < 50 µm) was determined using 6 × 6 mm macular swept-source optical coherence tomography images, and associated risk factors were investigated. Subfoveal choroidal thickness was measured, and its associated risk factors investigated. The overall prevalence of pachychoroids was 9.5%. Regression analysis showed that a younger age, shorter axial length, male sex, and smoking were significantly associated with the presence of pachyvessels (p = 0.047; odds ratio [OR] 0.96 per year, p = 0.021; OR 0.61 per 1 mm, p = 0.012; OR 3.08 vs. female, and p = 0.011; OR 3.15 vs. non-smoker, respectively) and greater choroidal thickness (p < 0.001, p < 0.001, p < 0.003, and p < 0.017, respectively). The results were consistent with other research findings which showed that pachychoroid-related disorders such as central serous chorioretinopathy were associated with younger age, male sex, shorter axial length, and smoking. Smoking may be associated with choroidal circulatory disturbance in the Japanese population.

Effect of internal limiting membrane peeling on visual field sensitivity in eyes with epiretinal membrane accompanied by glaucoma with hemifield defect and myopia.

PURPOSE: To investigate the effects of internal limiting membrane (ILM) peeling on visual field sensitivities in eyes with epiretinal membrane (ERM) accompanied by glaucoma with hemifield defect and myopia. STUDY DESIGN: Retrospective clinical study METHODS: We reviewed clinical records of patients with ERM who underwent vitrectomy and ERM/ILM peeling. We first collected clinical data of eyes with ERM and glaucoma with hemifield defect. We recorded visual field sensitivities at 52 points and analyzed differences between before and after surgery. We then compared the changes in visual field sensitivity between glaucomatous and normal hemifields. Next, we collected ERM eyes without glaucoma and stratified them into two groups based on axial length (threshold = 26.0 mm). In these eyes, we also recorded visual field sensitivities at 52 points and analyzed differences between before and after surgery. RESULTS: The study included 18 eyes with ERM and glaucoma with hemifield defect (11 men; mean age, 68.3 ± 7.2 years). These eyes showed significant sensitivity reductions at 5/26 points, mainly in the nasal area of the glaucomatous hemifield, whereas only 1/26 points exhibited significant sensitivity reduction in the normal hemifield. In eyes with axial length <26.0 mm and axial length ≥26.0 mm, 29 peripheral and seven superior peripheral points showed significant improvements in visual field sensitivities, respectively. CONCLUSION: Visual field sensitivity reduction occurred mainly in the nasal region of the glaucomatous hemifield. Differences in axial length alone were not a prominent risk factor for reduced visual field sensitivity after ILM peeling in eyes with ERM.

Investigation of causative factors for unusual shape of macula in eyes with macula-off rhegmatogenous retinal detachment.

PURPOSE: To determine the factors significantly associated with anterior protrusion of the macula in eyes with a macula-off rhegmatogenous retinal detachment (RRD) and to determine the relationship between the intraretinal cystoid cavities (ICCs) and the anterior protrusion and function of the fovea. STUDY DESIGN: Retrospective cross-sectional study. METHODS: Sixty-nine eyes of 69 patients with successfully reattached macula-off RRD were retrospectively analyzed. Six radial spectral-domain optical coherence tomographic (OCT) images were used to evaluate the effects of the ICCs on detached macula and to measure the angle of the retina at the macula as a parameter to evaluate the anterior protrusion of the detached retina. The findings were compared to other parameters. RESULTS: The mean angle of the retina at the macula was 143.1 ± 15.9° with a range of 108 to 172°. Preoperatively, 51 eyes (74%) had ICCs in the inner nuclear layer and/or the outer plexiform layer and Henle fiber layer complex, but none was present after surgery. Multivariate regression analyses revealed that the angle of the retina was significantly associated with the presence of ICCs (ß = -0.637, P<0.001) and the height of subretinal fluid (ß = -0.256, P = 0.005). Eyes with ICCs had poorer preoperative vision (P<0.001), narrower angle of the retina (P<0.001), and thicker subretinal fluid (P<0.001) than eyes without cavities. CONCLUSIONS: The anterior protrusion in eyes with macula-off RRD is associated with the presence of ICCs. The presence of ICCs can affect preoperative function and morphology but does not affect postoperative function and morphology.

Longitudinal Changes of Macular Curvature in Patients with Retinitis Pigmentosa.

Purpose: To investigate the longitudinal changes of the macular curvature in eyes with retinitis pigmentosa (RP) and to determine the factors associated with the changes. Methods: We reviewed the medical charts of 107 RP patients, for whom the axial length of their right eyes ranged from 21.5 to 26.0 mm and who had had been followed by spectral-domain optical coherence tomography (OCT). The OCT images at the initial and the most recent examinations were compared. The mean curvature of Bruch's membrane within 6 mm of the central macula obtained from the OCT images was evaluated as the mean macular curvature index (MMCI). Changes in the MMCI and their relationships with other clinical factors, including the ellipsoid zone (EZ) width, were assessed. Results: The MMCI decreased significantly in the vertical OCT images, from -15.47 × 10-5 µm-1 to -16.36 × 10-5 µm-1 (P = 0.008) during the mean observation period of 3.4 ± 1.4 years (mean ± SD). This indicated that the macular shape became more concave. The change to a steeper shape was more prominent in eyes with less photoreceptor degeneration and for which the EZ width was preserved at >2000 µm. In three eyes, the MMCI increased markedly by >5 × 10-5 µm-1, and this was accompanied by absorption of the macular edema. Conclusions: The macular curvature in RP eyes becomes more concave in eyes with preserved EZ width. Translational Relevance: Longitudinal changes of the macular curvature in RP should be considered in future therapies, such as the implantation of the retinal prosthesis.

Association between displacement and thickness of macula after vitrectomy in eyes with epiretinal membrane.

The purpose of this cross-sectional retrospective study was to determine the relationship between the retinal displacements and the retinal thickness in eyes with epiretinal membrane (ERM) after vitrectomy with internal limiting membrane (ILM) peeling. To accomplish this, we measured the retinal thickness using optical coherence tomography (OCT) and the retinal displacement using OCT angiography to obtain 3 mm × 3 mm en face images before, and 2, 4, and 8 weeks following the surgery from 20 eyes of 20 patients. The distance between the retinal vessel bifurcations and the fovea was significantly displaced centrifugally and asymmetrically in the 4 quadrants postoperatively (P < 0.001). The foveal avascular zone (FAZ) was significantly enlarged, and the central foveal thickness (CFT) and the inner nuclear layer (INL) thickness were significantly thinner postoperatively. The displacements were significantly correlated with the changes in the FAZ area (r = 0.717, P < 0.001), the CFT (r = - 0.702, P < 0.001), and the INL thickness (r = - 0.702, P < 0.001). In conclusion, the distance between the retinal bifurcations and the fovea was asymmetrically expanded after the surgery and was significantly correlated with the morphological changes. These results indicate that a horizontal macular contraction is correlated with vertical retinal contraction in the eyes with an ERM.

Genetic Spectrum of EYS-associated Retinal Disease in a Large Japanese Cohort: Identification of Disease-associated Variants with Relatively High Allele Frequency.

Biallelic variants in the EYS gene are a major cause of autosomal recessive inherited retinal disease (IRD), with a high prevalence in the Asian population. The purpose of this study was to identify pathogenic EYS variants, to determine the clinical/genetic spectrum of EYS-associated retinal disease (EYS-RD), and to discover disease-associated variants with relatively high allele frequency (1%-10%) in a nationwide Japanese cohort. Sixty-six affected subjects from 61 families with biallelic or multiple pathogenic/disease-associated EYS variants were ascertained by whole-exome sequencing. Three phenotype groups were identified in EYS-RD: retinitis pigmentosa (RP; 85.94%), cone-rod dystrophy (CORD; 10.94%), and Leber congenital amaurosis (LCA; 3.12%). Twenty-six pathogenic/disease-associated EYS variants were identified, including seven novel variants. The two most prevalent variants, p.(Gly843Glu) and p.(Thr2465Ser) were found in 26 and twelve families (42.6%, 19.7%), respectively, for which the allele frequency (AF) in the Japanese population was 2.2% and 3.0%, respectively. These results expand the phenotypic and genotypic spectrum of EYS-RD, accounting for a high proportion of EYS-RD both in autosomal recessive RP (23.4%) and autosomal recessive CORD (9.9%) in the Japanese population. The presence of EYS variants with relatively high AF highlights the importance of considering the pathogenicity of non-rare variants in relatively prevalent Mendelian disorders.

Correlations between intraretinal cystoid cavities and pre- and postoperative characteristics of eyes after closure of idiopathic macular hole.

Intraretinal cystoid cavities have been detected at the edges of macular holes (MHs) but their clinical characteristics and their relationship to the MH variables have not been determined. We measured the areas of the intraretinal cystoid cavity in 111 eyes with MHs in the OCT images preoperatively. Our results showed that the intraretinal cystoid cavities were located in the Henle fiber layer-outer nuclear layer (HFL-ONL) complex in 106 eyes and in the inner nuclear layer (INL) in 89 eyes. All were resolved after the initial vitrectomy to close the MH. The mean area of the cystoid cavity was greater in the HFL-ONL complex (55.9 ± 42.7 × 103 µm2) than in the INL (9.1 ± 9.8 × 103 µm2; P < 0.001). The area of the cystoid cavities was significantly correlated with the basal MH size (r = 0.465,P < 0.001), the external limiting membrane height (r = 0.793, P < 0.001), and the maximum retinal thickness (r = 0.757, P < 0.001). The area of the cystoid cavities was significantly correlated with the preoperative best-corrected visual acuity (BCVA; r = 0.361, P < 0.001), but not with the postoperative BCVA or the integrity of any of the outer retinal microstructural bands. The presence of intraretinal cystoid cavities was related to some morphological characteristics, but not to the postoperative BCVA or the restoration of the outer retinal bands.

DIAGNOSTIC CHARACTERISTICS OF POLYPOIDAL CHOROIDAL VASCULOPATHY BASED ON B-SCAN SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AND ITS INTERRATER AGREEMENT COMPARED WITH INDOCYANINE GREEN ANGIOGRAPHY.

PURPOSE: To examine the characteristics of polypoidal choroidal vasculopathy using B-scan optical coherence tomography angiography (OCTA), and determine the diagnostic criteria of polypoidal choroidal vasculopathy based on OCTA. METHODS: This retrospective case series included patients diagnosed with treatment-naïve polypoidal choroidal vasculopathy who underwent indocyanine green angiography (ICGA) and swept-source OCTA at baseline. We compared the characteristics of the polyps detected using B-scan OCTA and ICGA. Then, the diagnostic concordance of each polypoidal lesion between ICGA and OCTA was evaluated. RESULTS: Among 54 eyes of 52 patients, all 54 eyes showed flow signals indicating polyps on both ICGA and B-scan OCTA. All polyps on B-scan OCTA were detected as round/ring-like flow signals inside pigment epithelial detachments, incomplete round/ring-like flow signals overlaid with round/ring-like OCT structures inside pigment epithelial detachments, or flow signals adjacent to a pigment epithelial detachment notch. Using B-scan OCTA, 94.7% of the polypoidal lesions were detected by an independent evaluator with an overall accuracy of 92.6% for counting the polypoidal lesions per eye relative to ICGA and a Kappa value of 0.82. CONCLUSION: Polyp detection on B-scan OCTA demonstrates high accuracy and is comparable to that obtained on ICGA. B-scan OCTA could replace ICGA for the diagnosis of polypoidal choroidal vasculopathy.

Correlation between macular vessel density and number of intravitreal anti-VEGF agents for macular edema associated with branch retinal vein occlusion.

We evaluated whether the reduction of macular vessel density was correlated with the number of intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents in eyes with a branch retinal vein occlusion (BRVO). The mean vessel density was determined by optical coherence tomography angiography in 29 eyes with macular edema associated with a BRVO. Our results showed that the mean vessel density in the group that had a resolution of the macular edema after one anti-VEGF injection was significantly higher than group that had a recurrence of the macular edema (P = 0.028). Single regression analysis showed that the number of intravitreal injections was significantly correlated with the reduction of the modified vessel density (r = -0.421, P = 0.023) and systemic hypertension (r = 0.377, P = 0.044). Multiple stepwise regression analysis showed that the reduction of the modified vessel density (ß = -0.442, P = 0.009) and hypertension (ß = 0.403, P = 0.016) were independent factors associated with the number of intravitreal injections. We conclude that the vessel density reduction can be used to predict whether recurrences of the macular edema will develop after the initial anti-VEGF injection in eyes with macular edema associated with a BRVO.

Choroidal and retinal displacements after vitrectomy with internal limiting membrane peeling in eyes with idiopathic macular hole.

It has been reported that the macular region of the retina is displaced after vitrectomy with internal limiting membrane (ILM) peeling in eyes with macular hole (MH), but the displacements of the deeper layers of the eye, e.g. RPE and choroid are unclear following the surgery. We used optical coherence tomography (OCT) and OCT angiography (OCTA) to obtain 3 mm × 3 mm en face images before, and 2, 4, and 8 weeks following the vitrectomy with internal limiting membrane (ILM) peeling from 22 eyes of 22 patients with a MH. The OCT and OCTA images showed displacements of the fovea and choroidal intermediate vessels postoperatively. The degree of displacement of the choroid was significantly less than that of the retina (P < 0.001). The displacements of the choroidal bifurcations were significantly correlated to their preoperative distance from the optic disc (r = -0.467, P < 0.001) and they were significantly correlated with the retinal displacements (r = 0.535, P < 0.001). The retina was displaced inferiorly and centripetally, but these localized displacements were not observed in the choroid. In conclusion, clinicians need to be aware of these displacements when evaluating the subfoveal choroid following the surgery because the displacement is different between the retina and the choroid.

In Vitro Epiretinal Membrane Model and Antibody Permeability: Relationship With Anti-VEGF Resistance in Diabetic Macular Edema.

Purpose: Diabetic macular edema (DME) is characterized by an accumulation of fluid in the macula due to diabetic retinopathy. Currently, anti-VEGF drugs are the standard treatment worldwide for DME. This study aimed to assess whether the existence of epiretinal membrane (ERM) affects anti-VEGF efficacy, due to reduced permeability of the antibody through the ERM. Methods: We retrospectively examined clinical data of DME patients who underwent anti-VEGF treatment and evaluated whether clinical differences existed between DME eyes with ERM and those without ERM. We then created an in vitro ERM model using MIO-M1, ARPE-19, and NTI-4 cells on Transwell membranes and evaluated antibody permeability through this in vitro ERM model using fluorescently labeled antibodies. Results: Central retinal thickness (CRT) change between before and 1 month after first anti-VEGF treatment, as well as final CRT and final visual acuity 12 months after first anti-VEGF treatment, significantly differed between DME eyes with ERM and those without ERM. The in vitro ERM model led to production of collagen I in a manner similar to that of human ERM specimens. Fluorescence intensity of the lower chamber of the in vitro ERM model was significantly reduced in a dose-dependent manner. Conclusions: Clinical data analysis indicated that the existence of ERM in DME eyes lowered the efficacy of anti-VEGF treatment. Reduced antibody permeability through the in vitro ERM model suggested ERM presence was associated with resistance to anti-VEGF treatment in DME eyes with ERM.