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Objective In this study, we aimed to determine the characteristics of neovascular age-related macular degeneration (AMD) patients requiring frequent anti-vascular endothelial growth factor (VEGF) therapy. Methods This was a retrospective observational study involving the review of 32 eyes of 31 patients (25 men and six women, mean age: 74.3 years) treated with anti-VEGF injections for less than eight weeks and at least one year of follow-up. The subtype of macular neovascularization (MNV), follow-up duration, number of injections, visual acuity, and exudative changes during the study period were evaluated. Results Twenty-nine eyes (90.6%) had MNV under the retinal pigment epithelium (RPE), including 11 eyes with type 1 MNV and 18 eyes with polypoidal choroidal vasculopathy (PCV). Only three eyes had type 2 MNV (9.4%) above the RPE. The mean follow-up period was 28.7 ± 16.5 months, and the mean number of injections was 21.5 ± 11.8. The mean visual acuity [logarithm of the minimum angle of resolution (logMAR) units] was 0.19 ± 0.23 at the initial visit to our hospital, which decreased non-significantly to 0.24 ± 0.4 at the final visit (p=0.63). The exudation in four eyes (two with type 1 MNV and two with PCV) never resolved. The exudation remained in 27 eyes (84%) even after every four weeks of treatment, and it was present in five eyes (16%) in the treatment interval of eight weeks. Conclusions In the eyes receiving frequent anti-VEGF injections, the sub-RPE MNV might have affected the response to the treatment. Although patients requiring frequent anti-VEGF therapy did not have a significant decrease in their visual acuity, 84% of the eyes had exudations even with monthly injections., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2023, Taketani et al.)

Purpose: To determine the characteristics of eyes with treatment-naïve quiescent choroidal neovascularization (CNV) detected by optical coherence tomography angiography (OCTA)., Methods: Thirty-eight eyes of 37 treatment-naïve consecutive patients (30 men, 7 women, average 69.8 years) were studied. Quiescent CNVs were detected by OCTA (RTVue XR Avanti, Optovue, Fremont, CA) in all eyes. Swept-source OCT (SS-OCT; DRI-OCT, Topcon, Japan) confirmed the absence of exudation. The symptoms, visual acuity, CNV size, and status of the fellow eye were evaluated. Patients were followed longitudinally and the length of follow-up period and development of exudation were recorded for each patient. We also investigated patients' medical records from their referral hospitals in search of prior exudation., Results: All eyes with quiescent CNV were diagnosed at the initial visit with sub-retinal pigment epithelium CNVs, i.e., type 1 CNV, from the OCT and OCTA images. Prior exudation was confirmed in 15 eyes (39.5%) from their medical records of the referral hospitals. Symptoms were present in 18 eyes (47.3%). An exudative CNV was present in 12 of the fellow eyes. Exudation developed in 12 eyes (31.6%) during an average follow-up period of 25.1 months. One-half of the eyes had a prior exudation. The CNV at the baseline in eyes that developed exudation during the follow-up period was larger than eyes without exudation; however, the difference was not significant (0.59±0.47 vs 0.48±0.32 mm 2 , P = 0.50)., Conclusion: Quiescent CNVs will develop exudation in approximately 30% of the eyes during a mean 2-year follow-up period. These findings must be remembered when investigating quiescent CNVs that could not be distinguished from eyes with former active CNV and naturally deactivate CNV., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Purpose: To determine the degree of misalignment between the center of foveal avascular zone and the center of foveal photoreceptors in eyes with an idiopathic epiretinal membrane (ERM)., Methods: We reviewed the medical records of 61 eyes with an idiopathic ERM. A 3 × 3 mm area centered on the fovea was scanned with optical coherence tomography angiography before and at 6 months after surgery. The center of foveal avascular zone and the center of foveal photoreceptors were detected by en-face optical coherence tomography angiography images and sequential optical coherence tomography B-sections in the macular region. The presence or absence of ectopic inner foveal layers was also evaluated., Results: The mean distance from the center of foveal photoreceptors to the center of foveal avascular zone was 111.7 ± 106.8 µm in eyes with preoperative ERM. This distance was significantly correlated with the preoperative central foveal thickness (r = 0.33, P = 0.0104). Preoperatively, the ectopic inner foveal layers were present in 27 (44.3%) of 61 eyes. The foveal misalignment was greater in eyes with ectopic inner foveal layers than in those without ectopic inner foveal layers (158.6 ± 140.0 vs. 74.4 ± 45.4 µm, P < 0.0003). At 6 months after ERM surgery, the foveal misalignment was significantly reduced to 73.7 ± 48.0 µm (P = 0.0018)., Conclusion: Determining the degree of misalignment between the center of foveal avascular zone and the center of foveal photoreceptors might be a useful way to evaluate the degree of ERM traction.

Purpose: To report the 2-year outcomes of intravitreal aflibercept injections (IAIs) in Japanese patients with neovascular age-related macular degeneration (AMD) using a 1-month adjusted treat-and-extend (TAE) regimen., Design: Multicenter, prospective, nonrandomized, interventional study., Participants: Ninety-seven eyes of 97 patients with treatment-naive AMD were studied at 3 tertiary ophthalmological institutions., Methods: The patients were treated with 3 consecutive monthly IAIs followed by the TAE regimen with a 1-month adjustment for a maximum of 3 months. Our TAE regimen allowed us to shorten and extend the treatment intervals even after a 3-month or 1-month treatment interval, or both, were reached. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), and subfoveal choroidal thickness (SCT) were analyzed., Main Outcome Measures: The mean changes in the BCVA, CRT, and SCT from the baseline to 2 years after initiating the treatment were determined. In addition, the number of injections also was determined., Results: The mean BCVA significantly improved from 0.27 logarithm of the minimum angle of resolution (logMAR) units to 0.14 logMAR at 2 years (P < 0.01). The mean CRT decreased significantly from 307±132 μm to 202±76 μm at 2 years (P < 0.01). The mean SCT decreased significantly from 247±106 μm to 203±96 μm at 2 years (P < 0.01). Seventy eyes (72.2%) showed a dry macula at 2 years. The treatment interval at 2 years was 1 month in 20 eyes (20.6%), 2 months in 18 eyes (18.6%), and 3 months in 59 eyes (60.8%). In 49 (50.5%) eyes with a 3-month treatment interval immediately after the loading phase, no fluid was seen in 25 eyes (51.0%) for the duration of this study. The rest had switched to a more frequent scheme. The mean number of injections during the 2-year period was 13.0±3.9., Conclusions: Intravitreal aflibercept injections with a 1-month adjusted TAE regimen significantly improved the BCVA and CRT with a reduced number of injections at 2 years. The treatment interval was adjusted to extend to 3 months in 60% and to shorten to 1 month in 20% of the eyes at 2 years., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the foveal structure and vasculature in eyes with an idiopathic epiretinal membrane (ERM)., Methods: Forty-nine eyes of 48 patients with an idiopathic ERM were studied. The superficial foveal avascular zone (FAZ) was measured by optical coherence tomography angiography (OCTA; RTVue XR Avanti, Optovue Inc., Fremont, CA), and the central foveal thickness (CFT) was measured by swept source OCT (DRI-OCT, Topcon, Japan). Twenty eyes underwent vitrectomy with internal limiting membrane (ILM) peeling, and the FAZ and CFT were evaluated pre- and postoperatively. Forty-nine eyes of 49 age-matched healthy subjects were also examined as control., Results: The FAZ in eyes with an ERM was significantly smaller than that of the control eyes (0.188±0.16 mm2 vs 0.328±0.14 mm2, P<0.01). The CFT in eyes with an ERM was significantly thicker than that of control eyes (315±0.14 μm vs 193±0.14 μm, P<0.01). The size of the FAZ was strongly correlated with the CFT (ERM, R = -0.753; control, R = -0.61, both P<0.01). The postoperative size of the FAZ was not significantly different from the preoperative size (0.115 mm2 vs 0.128 mm2, P = 0.17) but the CFT was significantly thinner (370 μm vs 288 μm, P<0.01) after the vitrectomy with ILM peeling in 20 eyes., Conclusions: The results indicate that an ERM might affect the morphology and vasculature of not only the inner but also the outer retina before and after vitrectomy with ILM peeling. The FAZ area might have been affected by the ILM peeling., Competing Interests: The authors have no proprietary interest in any aspect of this paper. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Purpose: To observe choroidal blood vessels in cases sharply demarcated with retinal pigment epithelium (RPE) atrophy at the macular area using en-face optical coherence tomography angiography (OCTA) and standard en-face optical coherence tomography (OCT)., Methods: The retrospective study included 12 eyes (8 patients; 5 men, 3 women; average age, 64.3 years) with RPE atrophy seen by ophthalmoscopy. The macular areas with normal and atrophic RPE sections were examined using en-face OCTA with an 840-nm light source (RTVue XR Avanti; Optovue Inc), which system can obtain standard en-face OCT images at identical areas. Images on en-face OCTA and standard en-face OCT were compared with each other when the segmentation range was being set as the full thickness of the choroid by the attached software., Results: Choroidal blood vessels were seen as black on standard en-face OCT images in all cases. However, the choroidal vessels on OCTA were depicted as white in the RPE atrophic area and black in the normal areas., Conclusion: Choroidal blood vessels in the normal sections of RPE were visualized in black on standard en-face OCT and OCTA with an 840-nm light source; however, those in the atrophic parts were observed as white, or with bloodstream, on OCTA images. Choroidal blood vessels cannot be evaluated accurately in commercially available OCTA systems because of blockage of light by the RPE.

Optical coherence tomography angiography (OCTA) seems not to image the choroidal blood flow pattern in the normal individual because of the OCT light attenuation. Our purpose in the current study was to visualize the large choroidal blood flow pattern after subtraction of the choriocapillaris projection artifact in normal eyes non-invasively by swept source (SS) OCTA. Sixty-one eyes of 45 individuals (19 men, 26 women) without ocular disease were examined by SS-OCTA (AngioPlex Elite 9000, Zeiss, Germany). A 12 × 12 mm macular area was scanned. Subfoveal choroidal thickness (SCT) was measured, and the choroidal blood flow pattern in a slab of 30 µm width at one-half of SCT was analyzed. In examining the choroidal blood flow pattern, a slab that was between 30 to 60 µm posterior to the retinal pigment epithelium, in which the choriocapillaris blood flow was most clearly imaged, was used for the subtraction of the projection artifacts from the choriocapillaris on the stromal area of choroid. The ratio (%) of the choroidal blood flow area in the whole choroidal region was calculated after binarization. Thirty-four eyes of 27 individuals (12 men, 15 women) were also examined by spectral domain OCTA (SD-OCTA). After the subtraction, the middle and large choroidal blood flow were clearly visible in SS-OCTA in all eyes. The mean SCT was 297 ± 61 µm, and the mean ratio of the choroidal blood flow area was 27.3 ± 8.2%, which was significantly correlated with SCT (R = 0.738, P < 0.01). SD-OCTA did not show the choroidal blood flow pattern. In conclusion, removal of the projection artifacts of choriocapillaris can make the choroidal blood flow visible in SS-OCTA of normal eyes. Because the ratio of choroidal blood flow area was correlated with SCT, the choroidal blood flow might be an important factor related to the choroidal thickness.

Purpose: To compare the efficacy of the subthreshold micropulse laser (SML) to conventional laser (CL) in treating focal leakages of the retinal pigment epithelium (RPE) in the eyes with central serous chorioretinopathy (CSC)., Methods: Twenty-nine eyes of 28 patients with CSC and typical focal leakage were treated with CL or SML. Both treatments were made with a 577 nm yellow laser (CL: NIDEK MC-500, SML: IRIDEX IQ577). The percentage of eyes with a complete resolution, the distance of the laser burns from the fovea, and injury of the RPE after treatment were studied., Results: A complete resolution was seen in 10 of 15 eyes (66.7%) after CL and 9 of 14 eyes (64.3%) after SML (P = 0.89). The average distance from the foveal center to the leakage point was 1282±596 μm for eyes treated with CL and 1271±993 μm for eyes treated with SML (P = 0.4). Only three eyes treated with SML had treatment sites within 500 μm of the fovea. RPE damage determined by fundus autofluorescence was found in all eyes treated with CL and only one eye treated with SML (P<.01)., Conclusions: SML achieved equivalent therapeutic effects as CL but without RPE damage in eyes with CSC.

Purpose: To visualize choroidal blood flow in larger vessels in highly myopic eyes using a phenomenon of the projection artifact to in the sclera using optical coherence tomography angiography., Methods: The retrospective study included 92 eyes (54 patients) with greater than 8 diopters of myopia. All eyes were examined using optical coherence tomography angiography (RTVue XR Avanti; Optovue Inc, Fremont, CA). The blood flow in choroidal vessels was evaluated by attempting to directly segment the choroid and also by placing the segmentation layer behind the choroid, within the sclera. Subfoveal choroidal thickness was also measured at the same time. The authors also evaluated the 54 normal eyes (54 cases) without high myopia as a control group., Results: Segmentation artifacts occurred in 68 cases (73.9%) and precluded direct visualization of the choroidal blood flow in larger vessels. When the segmentation slab was placed posterior to the choroid within the sclera, the choroidal blood flow was visualized in 41 eyes (44.6%). The mean subfoveal choroidal thickness in eyes with visualization of choroidal blood flow was thinner than without visualization (50.3 ± 42.2 μm vs. 100.3 ± 44.4 μm, P < 0.01). Choroidal blood flow in larger vessels was imaged in no control eye., Conclusion: The choroidal vessel anatomy could be imaged by detecting flow using the projection artifact in the sclera with optical coherence tomography angiography. This technique may be useful in estimating the vascularity of the choroid.

Purpose: To evaluate the age-dependent morphologic alterations in the outer retina and choroid at the macula using swept-source optical coherence tomography (OCT)., Methods: Thirty eyes (30 normal subjects; average age, 49 years) were examined; five (age range, third-eighth decades of life) had refractive errors of ±2 diopters or less and no fundus abnormalities. An Early Treatment Diabetic Retinopathy Study (ETDRS) map of the outer retinal and choroidal thickness was constructed using swept-source OCT. The outer retinal and choroidal segmentation lines were drawn automatically, partially manually, within 6 millimeters of the macula., Results: The mean outer retinal and choroidal thicknesses in the 6-millimeter-diameter circle were 145±13 and 236±68 microns, respectively. The choroidal thickness and age were negatively (r = -0.66, P<0.01) correlated; the outer retinal thickness and age were not correlated (r = -0.16, P = 0.39). The outer retinal and choroidal thicknesses in the ETDRS map were not correlated (r = -0.13, P = 0.49) within 1 millimeter but correlated (r = 0.32, P<0.01) within 6 millimeters., Conclusions: The choroid thins with aging. The outer retina remains stable. Outer retina and choroid are correlated in the entire macula except for the center. ETDRS map can be useful for evaluation of the morphologic relationship between the outer retina and choroid.

Invasive aspergillosis is a rare disease and is often misdiagnosed. The clinical course is quite aggressive and it is a potentially fatal disease. We report a case of invasive aspergillosis involving the dura mater and optic nerves which was successfully treated with voriconazole, even though the patient had residual monocular blindness. An 86-year-old Japanese man complained of developing loss of vision in his left eye while taking oral fluconazole prescribed by an otolaryngologist for mycosis of the left maxillary sinus. He was referred to our hospital. At the first visit, he already had no light perception in the left eye, with decreased ocular motility in all directions and orbital apex syndrome. His corrected distance visual acuity (CDVA) in the right eye was 20/25 with enlargement of Mariotte's blind spot. Magnetic resonance imaging revealed inflammation around both optic nerves that also involved the dura mater. His antifungal therapy was changed to intravenous voriconazole. Although his right CDVA temporarily declined to 20/50, it improved to 20/16 by 10 months after the initiation of treatment. Maxillary sinus biopsy detected Aspergillus. Invasive aspergillosis progresses rapidly and aggressively. The present case highlights the importance of early diagnosis and selection of an appropriate antifungal agent.