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Purpose: To report a case of a full-thickness macular hole (FTMH) associated with a retinal pigment epithelium (RPE) tear after anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nvAMD), which was successfully closed by vitreous surgery. Observations: A 73-year-old man with nvAMD in the right eye received an intravitreal aflibercept injection due to enlarged pigment epithelial detachment. However, 2 days after the third injection, the patient experienced a sudden decline in vision. An FTMH with a tear in the underlying RPE was detected. The FTMH was closed using vitrectomy combined with the inverted internal limiting membrane (ILM) flap technique. Conclusions and Importance: Our case highlights a rare complication of both an FTMH and an RPE tear after anti-VEGF therapy. Vitrectomy, with the inverted ILM flap technique, proved effective in closing the FTMH despite the complexity of the case.

Objectives: To attain an understanding of pachyvein formation seen with central serous chorioretinopathy (CSC) by measuring the choroidal blood flow (CBF) velocity and to apply the findings to existing hydrodynamic theorems. Methods: Nineteen subjects with monocular CSC (mean age 51.8 ± 12.7 years) were included. Laser speckle flowgraphy measured the mean blur rate (MBR) in the foveal and perifoveal regions, and the findings were applied to the Equation of Continuity (Q = AV) and Bernoulli’s theorem (1/2V2 + P/ρ = constant). Results: The mean foveal/perifoveal MBRs in the CSC eyes were 6.4 ± 3.2/9.6 ± 3.2 (p < 0.001). The mean MBRs in the non-CSC eyes were 8.3 ± 3.2/7.9 ± 2.4 (p = 0.37). The significant foveal CBF velocity decrease in CSC eyes occurs because of exudation from the hyperpermeable choriocapillaris. The subsequent decrease in blood volume due to the exudation elicits a decrease in the blood flow velocity in the inferior venules in accordance with the Equation of Continuity. The decrease in the blood flow velocity may result in an elevated blood flow pressure in the inferior venules and veins at the exudation site, in accordance with Bernoulli’s theorem. Conclusion: A significant decrease in the foveal MBR may result from exudation from the hyperpermeable macular choriocapillaris. This decreased velocity may elicit a blood pressure elevation that can expand the inferior venules and veins at the exudation site, so-called pachyvein and pachychoroid formation. The application of hydrodynamic theorems to the measurement of ocular blood flow can provide new insights into the understanding of the pathogenesis of chorioretinal disease.

Background: Subretinal hyper-reflective material (SHRM) sometimes causes vision loss in spite of anti-vascular endothelial growth factor (VEGF) therapy in eyes with neovascular age-related macular degeneration (nvAMD). We evaluated the impacts of combination therapy with intravitreal ranibizumab (IVR) and tissue plasminogen activator (tPA) in eyes with nvAMD accompanying SHRM. Methods: In total, 25 eyes of 25 patients (16 men and 9 women, 76.7 years old), who underwent IVR/tPA for nvAMD with SHRM and were followed up for at least 12 months, were retrospectively reviewed. In total, 15 eyes were treatment-naïve and 10 eyes had previous treatment for nvAMD. Results: In total, 16 eyes had type 2 macular neovascularization (MNV), 5 eyes type 1 MNV with fibrovascular pigment epithelial detachment and 4 eyes polypoidal choroidal vasculopathy. At month 12, SHRM regressed or reduced in 18 eyes (72%) and the best-corrected visual acuity (BCVA) improved in 6 eyes (24%) and was unchanged in 14 eyes (56%), while the mean BCVA was just stabilized. The mean central retinal thickness, macular volume and SHRM thickness significantly improved from 408 µm to 287 µm, from 11.9 mm3 to 9.6 mm3, from 369 µm to 165 µm, respectively (p < 0.01). Conclusions: The combination therapy with IVR/tPA for nvAMD with SHRM may help preserve vision by prompt regression of SHRM.

A 47-year-old man presented with visual loss in the right eye 8 h after the first dose of a coronavirus disease 2019 (COVID-19) vaccine developed by Pfizer/BioNTech (BNT162b2). The best corrected visual acuity (BCVA) was 20/200. Fundus examination showed dilated and tortuous retinal veins at the posterior pole, retinal hemorrhages throughout the fundus, and macular edema. Fluorescein angiography showed multiple hypofluorescent spots that appeared to be fluorescent block due to retinal hemorrhages and hyperfluorescent leakage from the retinal veins. The eye was diagnosed with central retinal vein occlusion (CRVO). For the treatment of macular edema, intravitreal injection of aflibercept (IVA) was administered and treated with one plus pro re nata regimen. Five IVAs were performed over a 10-month follow-up period, with resolution of macular edema, and the BCVA recovered to 20/20. The patient was young and had no history of diabetes mellitus, hypertension, or atherosclerotic diseases, and his blood tests showed no abnormal findings. Both antigen test and polymerase chain reaction test for COVID-19 were negative, and the antibody test was positive due to vaccination. The development of CRVO in this patient may have been related to COVID-19 vaccination, and the appropriate IVA treatment resulted in a good visual prognosis.

(1) Background: Age-related Macular Degeneration (AMD) is a critical condition leading to blindness, necessitating lifelong clinic visits for management, albeit with existing challenges in monitoring its long-term progression. This study introduced and assessed an innovative tool, the AMD long-term Information Viewer (AMD VIEWER), designed to offer a comprehensive display of crucial medical data—including visual acuity, central retinal thickness, macular volume, vitreous injection treatment history, and Optical Coherent Tomography (OCT) images—across an individual eye’s entire treatment course. (2) Methods: By analyzing visit frequencies of patients with a history of invasive AMD treatment, a comparative examination between a Dropout group and an Active group underscored the clinical importance of regular visits, particularly highlighting better treatment outcomes and maintained visual acuity in the Active group. (3) Results: The efficiency of AMD VIEWER was proven by comparing it to manual data input by optometrists, showing significantly faster data display with no errors, unlike the time-consuming and error-prone manual entries. Furthermore, an elicited Net Promoter Score (NPS) of 70 from 10 ophthalmologists strongly endorsed AMD VIEWER’s practical utility. (4) Conclusions: This study underscores the importance of regular clinic visits for AMD patients. It suggests the AMD VIEWER as an effective tool for improving treatment data management and display.

Purpose: This study aims to investigate the factors influencing post-treatment visual acuity (VA) in patients with central retinal vein occlusion (CRVO) with macular edema (ME). Methods: The subjects of this study were patients who visited our clinic from May 2013 to July 2019 and who could be followed up with for at least 12 months. Cases with hemi CRVO were excluded from this study. Factors considered in the evaluation of visual prognosis at the 12 months included initial best-corrected VA, central subfoveal thickness, CRVO subtype (nonischemic, ischemic, or converted from nonischemic to ischemic), time taken for the first treatment, number of anti-vascular endothelial growth factor agent injections, structural changes in the inner and outer retinal layers, and the presence of macular ischemia in a multiple regression analysis. Results: There were 41 patients with 41 eyes, 27 males and 14 females. The mean age of the patients was 70.5 ± 12.2 (mean ± standard deviation) years. The mean VA was 0.544 ± 0.576, 0.456 ± 0.568, and 0.586 ± 0.665 at the initial visit, 12 months later, and time of last observation, respectively. There were no significant differences in VAs observed between the baseline, month 12, and final visit. Multiple regression analysis revealed that the external limiting membrane score at month 12 (p = 0.030), the VA at initial visit (p < 0.001), and the presence of severe macular ischemia (p < 0.001) were the key factors associated with VA at month 12. Moreover, severe macular ischemia was identified as the only factor affecting decimal VA less than 20/200 at the last observation (p = 0.0092). Conclusions: Severe macular ischemia is strongly linked to a poor visual prognosis in patients with ME associated with CRVO.

Short-pulse laser is popular for its advantages like less pain. However, its effectiveness is still debated. The aim of this study was to compare fundus autofluorescence (FAF) luminosity changes of laser photocoagulation scars between the conventional laser (0.2 s) and the short-pulse laser (0.02 s) for diabetic retinopathy. Conventional and short-pulse laser photocoagulations were performed in six and seven eyes, respectively. FAF images were captured at 1, 3, 6, 12, and 18 months after the treatments. To evaluate FAF, individual gray-scale values of the laser scars adjacent to the retinal arcade vessels were recorded; then, the mean gray values of the scars were divided by the luminosity of arcade vein. The average luminosity ratio of laser scars at 1, 3, 6, 12, and 18 months were 1.51 ± 0.17, 1.26 ± 0.07, 1.21 ± 0.03, 0.95 ± 0.11, and 0.89 ± 0.05 with conventional laser and 1.91 ± 0.13, 1.50 ± 0.15, 1.26 ± 0.08, 1.18 ± 0.06, and 0.97 ± 0.04 with short-pulse laser, respectively. Findings suggest the short-pulse laser displayed delayed hypoautofluorescence progression. This implies potential postponement in post-irradiation atrophic changes, as well as metabolic amelioration delay in the ischemic retina, when compared to conventional laser treatment.

We evaluated the long-term prognosis of the eyes of patients with polypoidal choroidal vasculopathy (PCV) treated with photodynamic therapy (PDT). In total, 60 eyes of 57 patients diagnosed with PCV and treated with PDT were reviewed retrospectively in real-world settings. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), anatomical findings (vision-threatening findings), and treatment history were assessed. In total, 38 eyes underwent PDT as the initial treatment (initial PDT group) and 22 eyes underwent PDT as a rescue treatment (rescue PDT group). In the initial PDT group, 11 eyes (29%) did not require additional therapy throughout the observation period and maintained good BCVA. A total of 27 eyes (71%) underwent additional treatments and the mean BCVA was only stabilized for 2 years; thereafter, decreased vision occurred even with additional treatments. In the rescue PDT group, 22 eyes (95%) required additional treatment. Hard exudate, serous pigment epithelial detachment, and the total vision-threatening score were related to worse BCVA. Initial PDT may be effective in about 30% of cases with preservation of good vision and no need for additional treatment. However, patients with received rescue PDT needed additional treatment in most cases and the vision decreased in many cases.

Background and Objectives: This study aimed to elucidate the role of laser photocoagulation therapy in the treatment of diabetic macular edema (DME) as an alternative to, or in conjunction with, the first-line treatment, anti-vascular endothelial growth factor (VEGF). Materials and Methods: A comprehensive literature search to identify studies that evaluated the efficacy of laser photocoagulation therapy in the management of DME was performed. The relevant findings of the efficacy of focal/grid laser therapy from data in randomized, controlled trials were synthesized, and the potential of new laser technologies, such as navigated laser systems, pattern scan lasers, and subthreshold lasers, was explored. The usefulness of multimodal imaging-guided laser therapy was also evaluated, with a focus on the potential contribution to anti-VEGF therapy. Results: Focal laser photocoagulation targeting microaneurysms remains an effective therapeutic approach to chronic refractory edema, despite the widespread use of anti-VEGF therapy. To achieve the best possible treatment outcomes, precise identification of microaneurysms is essential. This requires the use of multimodal imaging-guided, highly accurate, minimally invasive coagulation techniques. Subthreshold laser therapy can also reduce the frequency of anti-VEGF injections and minimize treatment burden. Conclusions: Further studies are needed to determine the optimal timing and settings for laser photocoagulation therapy and the potential of new laser technologies in the management of DME. Nevertheless, laser photocoagulation therapy plays an important role in the management of DME, in conjunction with anti-VEGF therapy.

Intravitreal injection of triamcinolone acetonide (TA) is essential for clinical treatment in patients who insufficiently respond to vascular endothelial factor inhibitors for diabetic macular edema (DME). The aim of this study was to investigate microvascular changes treated with TA using optical coherence tomography angiography (OCTA). After TA in twelve eyes of eleven patients with central retinal thickness (CRT), there was a 20% or more reduction observed. Visual acuity, the number of microaneurysms, vessel density, and the foveal avascular zone (FAZ) area were compared before and at 2 months after TA. At baseline, the number of microaneurysms was 2.1 ± 1.1 in the superficial capillary plexuses (SCP) and 2.0 ± 1.1 in the deep capillary plexuses (DCP), with a significant decrease post-treatment to 1.0 ± 1.0 for SCP and 0.8 ± 0.8 for DCP (SCP; p = 0.018, DCP; p = 0.008). There was significant enlargement of the FAZ area from 0.28 ± 0.11 mm2 to 0.32 ± 0.14 mm2 (p = 0.041). There was no significant difference in the visual acuity and vessel density of SCP and DCP. Results indicated that OCTA was useful for the evaluation of qualitative and morphological retinal microcirculation and that intravitreal TA may decrease microaneurysms.

Abstract Intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is the standard treatment modality in various types of retinal diseases. However, endophthalmitis remains the most serious complication. Despite the lack of evidence that antibiotics prevent endophthalmitis, topical antibiotics are still used routinely in Japan. We conducted a retrospective multicenter study by analyzing records from patients who underwent IVI of anti-VEGF agents with or without antibiotic treatment. In the analysis of a total of 147,440 eyes, the incidence of endophthalmitis was 0.007%: 0.005% with no use of antibiotics, 0.009% with antibiotic pretreatment, 0.012% with posttreatment, and 0.005% with pre- and posttreatment. There was no statistically significant difference among the four groups (chi-square test, p = 0.57). Most facilities used masks, sterilized gloves, and drapes. Nine of the 10 eyes that developed endophthalmitis received topical antibiotics, and all infected eyes underwent IVI with aflibercept, not the prefilled syringe delivery system. In four patients who received multiple IVI, the detection of causative bacteria revealed resistance to used antibiotics. Data from this large population, treated with or without antibiotics, suggests that antibiotic prophylaxis does not reduce the rate of endophthalmitis after IVI.

Purpose: To report an accidental case of traumatic macular hole caused by Nd:YAG laser in a dermatology clinic. Observations: A 24-year-old woman sustained a laser injury to her right eye while practicing a dermatologic treatment using a Nd:YAG laser without wearing protective goggles. She noticed sudden-onset and progressing visual loss in her right eye and consulted an ophthalmologist 2 days after injury. The best-corrected visual acuity (BCVA) of her right eye decreased to 20/133. Fundus examination showed white parafoveal flecks with a central retinal hemorrhage and underlying serous retinal detachment. The retinal sensitivity in this lesion deteriorated. Two weeks later, a full-thickness macular hole (FTMH) developed in the affected eye. She was referred to Nagoya City University Hospital where the laser damage described was observed. The BCVA was 20/67. She underwent pars plana vitrectomy performed using the inverted internal limiting membrane (ILM) flap technique and gas tamponade. One week postoperatively, the FTMH closed, the BCVA in her right eye improved to 20/50, and the retinal sensitivity in the macular area mostly improved. The BCVA gradually improved and reached 20/25 9 months after the injury. Conclusions and importance: Protective goggles must be worn when using an Nd:YAG laser in the laboratory or clinical setting. In the unfortunate event of a FTMH, early vitrectomy with an inverted ILM flap technique can be helpful to achieve a good visual prognosis.

PurposeTo investigate the clinical features, treatment options, and visual outcomes of submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD).DesignA retrospective, observational case series.MethodsSetting: Multicenter institutional setting. Patient Population: A total of 127 patients (127 eyes; 88 men, 39 women; (mean age, 74.2 years)) diagnosed with AMD-associated SMHs exceeding 2 disc diameters involving the fovea. Observation: The AMD types, previous treatments, treatment options, anatomic findings, and best-corrected visual acuity (BCVA) were assessed. Main Outcome Measures: Clinical features, treatment options, and visual outcomes of SMHs secondary to nAMD.ResultsThirty-two eyes had typical AMD, 94 eyes polypoidal choroidal vasculopathy (PCV), and one eye retinal angiomatous proliferation. Eighty-five eyes were treatment-naïve; 42 eyes were treated previously: anti-vascular endothelial growth factor (VEGF) therapy (n = 26), photodynamic therapy (n = 3), and combined therapy (n = 13). Treatment of SMHs included vitrectomy (36 eyes), pneumatic displacement (49 eyes), and anti-VEGF monotherapy (42 eyes). The final BCVA improved significantly in treatment-naïve cases from 0.86 to 0.62 logarithm of the minimal angle of resolution (logMAR) unit (Snellen equivalent from 20/145 to 20/83) and from 0.80 to 0.56 (Snellen equivalent from 20/126 to 20/73) in PCV cases. Meanwhile, the BCVA logMAR values improved from 1.15 to 0.75 (Snellen equivalent from 20/283 to 20/112) and from 0.87 to 0.63 (Snellen equivalent from 20/148 to 20/85) in eyes that underwent vitrectomy or pneumatic displacement, respectively. In eyes with BCVAs between 20/133 to 20/40 at SMH onset, the final VA in the pneumatic displacement group was better than in the anti-VEGF monotherapy group. One eye had a retinal detachment and 1 eye had a macular hole in the vitrectomy group, and 5 eyes had a vitreous hemorrhage in the pneumatic displacement group.ConclusionsThe recommended treatment for SMHs secondary to nAMD exceeding 2 disc area and with BCVA below 20/40 is vitrectomy or pneumatic displacement for visual improvement.

PurposeTo evaluate the progression of early age-related macular degeneration to neovascular age-related macular degeneration (nAMD), and identify the abnormal fundus autofluorescence (FAF) patterns and markers of choroidal neovascularization (CNV) in fellow eyes of patients with unilateral nAMD.MethodsSixty-six patients with unilateral nAMD who developed abnormal FAF in the fellow eyes were enrolled in this multicenter, prospective, observational study, and followed-up for 5 years. FAF images on Heidelberg Retina Angiogram Digital Angiography System (HRA) or HRA2 were classified into eight patterns based on the International Fundus Autofluorescence Classification Group system. The patients in which the fellow eyes progressed to advanced nAMD, including those who did not develop nAMD, were assessed based on the following factors: baseline FAF patterns, age, sex, visual acuity, drusen, retinal pigmentation, baseline retinal sensitivity, family history, smoking, supplement intake, hypertension, body mass index, and hematological parameters.ResultsOf the 66 patients, 20 dropped out of the study. Of the remaining 46 patients, 14 (30.42%, male: 9, female: 5) progressed to nAMD during the 5-year follow-up. The most common (50% eyes) FAF pattern in the fellow eyes was the patchy pattern. According to the univariate analysis, CNV development was significantly associated with age, supplement intake, and low-density lipoprotein levels (pConclusionThe fellow eyes (with abnormal FAF) of patients with unilateral nAMD may progress from early to advanced nAMD. However, no FAF pattern was found that predicted progression in nAMD.

Individuals with pachydrusen, larger than 125 μm, have a significantly thicker choroid than do those with soft drusen or reticular pseudodrusen. Little is known about cases of abnormal blood flow within pachydrusen. The purpose of this report was to demonstrate a blood flow signal within pachydrusen using optical coherence tomography (OCT) angiography. A 76-year-old Japanese woman presented with innumerable drusen/pachydrusen in both posterior poles. Her visual acuity was good. OCT showed subfoveal pachydrusen in the left eye, but no exudative changes. The subfoveal choroidal thickness was increased to 274 μm in the left eye. OCT angiography revealed a blood flow signal within the pachydrusen. However, fluorescein and indocyanine green angiographies indicated no abnormal hyperfluorescent lesion in the macula of the left eye. During the 13-month follow-up, the blood flow signal in OCT angiography did not change in diameter, and no exudative change was observed. The blood flow signal may have properties of capillary blood vessels derived from the choriocapillaris, rather than angiogenic vessels from choroidal neovascularization or polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization.

PurposeTo evaluate the clinical characteristics, treatment trends, and visual prognosis of submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD) and retinal arterial macroaneurysm (RAM).MethodsThis retrospective study enrolled 187 Japanese patients with SMH at 10 institutions from 2015 to 2018. Medical records including SMH etiology, best-corrected visual acuity (BCVA), fundus photographs, optical coherence tomography images, and selected treatments were analyzed.ResultsMajor causes of SMH were typical nAMD (tnAMD) (18%), polypoidal choroidal vasculopathy (PCV) (50%) and RAM (29%). Age, male/female ratio, baseline BCVA, central retinal thickness, and involved retinal layers were significantly different between etiologies (all PConclusionsThe characteristics of, and treatment strategy for, SMH were different between the underlying diseases. Anti-vascular endothelial growth factor treatment with or without expansile gas was mainly chosen for SMH in tnAMD and PCV, whereas vitrectomy with gas was the most common treatment for RAM, and the higher rate for vitrectomy might result in the greater BCVA improvement in the RAM group than in the other groups. Final BCVA was better in PCV, RAM, and tnAMD, in that order, because patients with PCV were younger and had better baseline BCVA.

Purpose: To report family members with familial retinal arteriolar tortuosity (FRAT) identified after sudden visual loss. Observations: A 15-year-old boy had sudden visual loss in his left eye while playing on a horizontal bar. He was referred to Nagoya City University Hospital from an eye clinic. The ophthalmologic examination showed retinal hemorrhage bilaterally. His best-corrected visual acuity (BCVA) was 20/17 in the right eye and 20/67 in the left eye. Bilateral retinal arteriolar tortuosity as well as retinal hemorrhage was seen. Since his mother with 54 years of age also had a history of retinal hemorrhage that improved spontaneously, fundus examination was performed, revealing tortuosity of the retinal arterioles. Consequently, the patient and his mother were diagnosed as FRAT. He was followed without intervention. Retinal hemorrhage gradually decreased and resolved after 3 months. The BCVA of his left eye gradually improved and reached 20/20 after 1 year. Conclusions and importance: In this case, the family history was very useful for early diagnosis. Immediate and accurate diagnosis allowed the patient to be followed without intervention and achieve subsequent resolution of retinal hemorrhage and improved vision. FRAT should be considered in cases of sub-internal limiting membrane hemorrhages in young patients even in the presence of discrete retinal arteriolar tortuosity.

We wish to demonstrate that theorems of fluid dynamics may be employed to hydrodynamically analyze the clinical presentations seen within the pachychoroid-spectrum diseases (PSD). Methods: We employed both the Equation of Continuity Q = A · V in which Q represents blood flow volume, A the sectional area of a vessel, and V blood flow velocity as well as Bernoulli’s Principle 1/2 V2 + P/ρ = constant where V represents blood flow velocity, P static blood pressure and ρ blood density. The Equation of Continuity states that a decrease in flow volume occurs simultaneously with a decrease in the flow velocity and/or sectional area, and vice versa. Bernoulli’s Principle states that a decrease in the velocity of a fluid occurs simultaneously with an increase in static pressure, and vice versa. Results: Hyperpermeability of the choriocapillaris, as visualized on fluorescein angiography and indocyanine green angiography (ICGA), causes a fluid exudation and, therefore, a decrease in the blood flow volume Q which elicits a simultaneous decrease in the blood flow velocity V clinically observable in filling delay into the choriocapillaris on ICGA. An increase in the static blood pressure P will simultaneously occur in venules in accord with Bernoulli’s Principle. Conclusions: A decrease in the blood flow velocity in the choriocapillaris due to its hyperpermeability will hydrodynamically elicit an increase in the blood pressure in venules. This blood pressure rise may expand Sattler and Haller veins, forming pachyveins. The primary lesion of PSD can be in pigment epithelium and choriocapillaris.

Purpose: To report a case with focal choroidal excavation (FCE) accompanied by type 2 choroidal neovascularization (CNV), in which the CNV was successfully treated with intravitreal aflibercept, after which the FCE was no longer detectable. Observations: A conforming type of FCE was detected in the left eye of a 34-year-old Japanese man who visited our hospital for a second opinion regarding treatment for his right eye. Three months later, type 2 CNV developed in the region corresponding to the FCE in the left eye. After treatment with intravitreal aflibercept, the CNV disappeared, and FCE was no longer detected. No recurrence has been observed in the 12 months following the treatment. Conclusions and Importance: Although the etiology of FCE has not been fully elucidated, we discussed the mechanisms underlying its occurrence, its association with CNV, and the disappearance of both conditions after treatment.

A 37-year-old woman presented with painful visual loss in the left eye for 2 weeks. The best-corrected visual acuity was 20/200. Ophthalmic examination of the left eye revealed vitreous cells, optic disc swelling, serous retinal detachment, and macular star-figure hard exudates. Swept-source optical coherence tomography showed both inner and outer retinas were swollen, the choroid was thickened, and the corresponding retinal pigment epithelium was elevated. Wide-field indocyanine green angiography disclosed multiple hypofluorescent spots in the mid-periphery. Taken together, an involvement of optic disc, entire retina, and choroid was considered in the current case.

Purpose: Acquired vitelliform lesions (AVLs) are associated with age-related macular degeneration and other variable macular disorders. AVLs often lead to outer retinal atrophy, sometimes accompanying a macular hole and choroidal neovascularization. The purpose of this study was to report a rare case with bilateral AVLs, in which one eye had accompanied a macular hole and the second eye a serous pigment epithelial detachment (sPED). Observations: A 66-year-old woman complained of bilateral metamorphopsia. AVLs were observed in the right eye and a flat sPED in the left eye. The best-corrected visual acuity (BCVA) was 20/17 in both eyes. Fluorescein angiography revealed local leakage in the right eye and pattern dystrophy-like hypofluorescence in both eyes. The sPED progressed with AVLs in the left eye and was treated with a combination therapy of intravitreal aflibercept, a sub-Tenon's injection of triamcinolone acetonide, and photodynamic therapy (IVA/STTA/PDT), which successfully flattened the sPED and sustained good vision for 4 years. The right eye was treated with intravitreal ranibizumab and tissue plasminogen activator, which enhanced absorption of the vitelliform material. However, 14 months later, a macular hole with typical metamorphopsia formed above a subretinal fibrotic scar at the vitelliruptive stage. Although pars plana vitrectomy closed the macular hole, enlargement of the outer retinal atrophy worsened the BCVA to 20/100. Conclusions and importance: We successfully treated one eye with a sPED with AVLs using the combination therapy of IVA/STTA/PDT, while the second eye with a macular hole secondary to AVLs ultimately developed outer retinal atrophy with visual loss.

Age-related macular degeneration (AMD) is a late-onset progressive blinding disease. We established human induced pluripotent stem cells (iPSCs) from an AMD patient. The generated iPSC line showed pluripotency markers and three-germ layer differentiation ability in vitro. This iPSC line will be useful for elucidating the pathomechanisms of and drug discovery for AMD.

Best Disease is an inherited retinal dystrophy that results in progressive and irreversible central vision loss caused by mutations of BESTROPHIN1 (BEST1). We established human induced pluripotent stem cells (iPSCs) from a Best disease patient with mutations R218H and A357V in the BEST1 gene. The generated iPSCs showed pluripotency markers and three-germ layer differentiation ability in vitro. A genetic analysis revealed mutations of R218H and A357V in the iPSCs. This iPSC line will be useful for elucidating the pathomechanisms of and drug discovery for Best disease.

PURPOSE:To assess the 5-year change in abnormal fundus autofluorescence (FAF) patterns and retinal sensitivity in the fellow eye of Japanese patients with unilateral exudative age-related macular degeneration (AMD). METHODS:Patients with unilateral exudative AMD who developed abnormal FAF in the fellow eyes were enrolled. FAF imaging and microperimetry were performed at baseline and follow-ups. FAF findings were classified into 8 patterns based on the International Fundus Autofluorescence Classification Group to assess retinal sensitivity. Forty-five points covering the central 12 degrees on microperimetry were superimposed onto the FAF images. Each point was classified depending on the distance from the abnormal FAF. "Close" was defined as the portion within 1 degree from the border of any abnormal FAF, and "Distant" was defined as the portion over 1 degree from the border of abnormal FAF. To investigate the association between the retinal sensitivity and distance from the abnormal FAF, hierarchical linear mixed-effect models were used with the distance, time and time squared from baseline (months), and angle (degrees) as fixed effects. Differences among patients, eyes, and test point locations were considered successively nested random effects. RESULTS:We studied 66 fellow eyes with abnormal FAF. Twenty-seven eyes were followed-up during the 5 years. In the 13 of 27 eyes (48%), the abnormal FAF patterns had changed during the 5 years. We found retinal sensitivity was associated significantly with the distance from the abnormal FAF ("Distant": p

Purpose: Hypotonic maculopathy secondary to cyclodialysis often persists and causes irreversible visual loss despite a variety of treatments proposed. The purpose of this study is to report two cases with persistent hypotonic maculopathy due to a large cyclodialysis cleft treated with a simple, lens-sparing technique of external drainage, diathermy, and suturing under the placement of an infusion cannula. Observations: Both patients had sustained blunt trauma to one eye, causing persisting hypotonic maculopathy. One eye was phakic. The ciliary body was totally detached with a large cyclodialysis cleft. After half-thickness scleral flaps were made and a 25-gauge infusion cannula was placed at the pars plana, external drainage was performed. Transscleral diathermy and interrupted suturing also were done. Results: In both cases, the ciliary detachment promptly improved and the intraocular pressure normalized after transient elevation for a few days. No adverse events were observed. Conclusions and importance: We successfully treated two cases with hypotonic maculopathy by a simple technique with an infusion cannula. This procedure is simple, immediately effective, less invasive, and applicable to all cases including phakic eyes. Keywords: Blunt trauma, Ciliary body detachment, Cyclodialysis, External drainage, Hypotonic maculopathy, Infusion cannula

Abstract Background The purpose of this study is to report wide-field angiography findings before and after steroid therapy in a case with bilateral Vogt-Koyanagi-Harada (VKH) disease. Results A 44-year-old woman presented with bilateral blurred vision and metamorphopsia accompanied by symptoms of headache and tinnitus. The baseline best-corrected visual acuity was 20/20 in both eyes. Ophthalmic examination revealed a shallow anterior chamber and panuveitis accompanied by multiple serous retinal detachments in both eyes and ciliochoroidal detachments in the left eye. Wide-field fluorescein angiograms showed hyperfluorescene indicating pooling corresponding to multiple serous retinal detachments in the posterior lesion and vascular leakage in the peripheral retina and choroid, resolved after steroid tapering therapy. Interestingly, wide-field indocyanine angiograms revealed narrowing of choroidal vessels in the acute phase and its normalization with resolution of inflammation after the therapy. Conclusions Eyes with Vogt-Koyanagi-Harada disease had peripheral chorioretinal vascular leakage and choroidal vessel narrowing in the acute phase. Wide-field angiography is a useful tool to reveal peripheral chorioretinal findings and assess diameters and density of choroidal vessels.

Purpose: To report a case of hypertensive choroidopathy with bilateral bullous serous retinal detachments (SRDs), retinal pigment epithelial detachments (PEDs), and giant retinal pigment epithelial (RPE) tears. Observations: A 68-year-old man with a history of hypertension and diabetes mellitus presented with bilateral visual loss of about 10 day's duration. He discontinued his oral medications for 2 months without the advice of a physician. At his first visit, the best-corrected visual acuities (BCVAs) were 0.02 in the right eye and 0.3 in the left eye (decimal notation), and the respective intraocular pressures were 15 and 13 mmHg. Bullous SRDs, large PEDs, and giant RPE tears were present bilaterally. Blot retinal hemorrhages and hard exudates were seen in the left eye. The systemic blood pressure was 231/77 mmHg, and bilateral lower leg edema was observed. Biochemical blood tests showed deteriorated renal function, hypoalbuminemia, and hyperglycemia. Ultra-wide-field fundus fluorescein angiography showed leakage at the areas of the SRDs and hyperfluorescent areas corresponding to the RPE tears bilaterally. Indocyanine green angiography showed hypofluorescent areas corresponding to the PEDs. Systemic computed tomography and magnetic resonance imaging were performed, and no malignancy was found. Based on these findings, hypertensive choroidopathy was diagnosed. A week after antihypertensive treatment, the SRDs and PEDs resolved bilaterally, and the BCVAs improved to 0.4 and 0.5 in the right and left eyes, respectively. The RPE tears remained in both eyes, although the SRDs and PEDs did not recur. Conclusions and importance: Hypertensive choroidopathy must be considered in the differential diagnosis of SRDs and/or PEDs. Keywords: Hypertensive choroidopathy, Retinal pigment epithelial detachment, Fluorescein/indocyanine green fundus angiography, Diabetic nephropathy

We investigated the rates of the use of steroids in Japanese central serous chorioretinopathy (CSC) cases and differences in the characteristics of CSC with and without steroids. A total of 538 eyes of 477 patients diagnosed with CSC, with 3 months or more of follow-up between April 2013 and June 2017 at 8 institutions. Patients with CSC with more than 3 months of follow-up were identified by OCT and fluorescein angiography at 8 institutions. Data collected included patient demographics, history of corticosteroid medication and smoking, spherical errors, findings of angiography, subfoveal choroidal thickness, and changes through the follow-up period. Differences in these findings were analyzed in cases with and without corticosteroid treatment. Among the 477 patients (344 men,133 women), 74 (15.5%) (39 men, 35 women) underwent current or prior steroid treatment. Cases with steroids were higher age (p = 0.0403) and showed no male prevalence, more bilateral involvement (p < 0.0001), and the affected eyes had multiple pigment epithelial detachment (p

PurposeAbnormal fundus autofluorescence (FAF) potentially precedes onset of late age-related macular degeneration (AMD) in Caucasian patients. Many differences exist between Asian and Caucasian patients regarding AMD types and severity, gender, and genetic backgrounds. We investigated the characteristics of abnormal FAF and retinal sensitivity in the fellow eyes of Japanese patients with unilateral neovascular AMD.MethodsSixty-six patients with unilateral neovascular AMD and abnormal FAF in the fellow eye were enrolled in this multicenter, prospective, observational study. The best-corrected visual acuity, fundus photographs, FAF images, and retinal sensitivity on microperimetry were measured periodically for 12 months. The FAF images were classified into eight patterns based on the International Fundus Autofluorescence Classification Group. The points measured by microperimetry were superimposed onto the FAF images and fundus photographs and classified as "within," "close," and "distant," based on the distance from the abnormal FAF and other findings. The relationship between the location of the baseline abnormal FAF and retinal sensitivity was investigated.ResultsIn Japanese patients, patchy (33.3%) and focally increased (30.3%) patterns predominated in the abnormal FAF. Intermediate-to-large drusen was associated predominantly with hyperfluorescence and hypofluorescence. Neovascular AMD developed within 1 year in six (9.1%) eyes, the mean baseline retinal sensitivity of which was 12.8 ± 4.7 dB, significantly (pConclusionIn Japanese patients, patchy and focally increased patterns predominated in the abnormal FAF. The retinal sensitivity was lower close to/within the abnormal FAF. FAF and microperimetry are useful to assess macular function before development of neovascular AMD or geographic atrophy.

Purpose. Although optical coherence tomography (OCT) is essential for ophthalmologists, reading of findings requires expertise. The purpose of this study is to test deep learning with image augmentation for automated detection of chorioretinal diseases. Methods. A retina specialist diagnosed 1,200 OCT images. The diagnoses involved normal eyes (n=570) and those with wet age-related macular degeneration (AMD) (n=136), diabetic retinopathy (DR) (n=104), epiretinal membranes (ERMs) (n=90), and another 19 diseases. Among them, 1,100 images were used for deep learning training, augmented to 59,400 by horizontal flipping, rotation, and translation. The remaining 100 images were used to evaluate the trained convolutional neural network (CNN) model. Results. Automated disease detection showed that the first candidate disease corresponded to the doctor’s decision in 83 (83%) images and the second candidate disease in seven (7%) images. The precision and recall of the CNN model were 0.85 and 0.97 for normal eyes, 1.00 and 0.77 for wet AMD, 0.78 and 1.00 for DR, and 0.75 and 0.75 for ERMs, respectively. Some of rare diseases such as Vogt–Koyanagi–Harada disease were correctly detected by image augmentation in the CNN training. Conclusion. Automated detection of macular diseases from OCT images might be feasible using the CNN model. Image augmentation might be effective to compensate for a small image number for training.

The technologies of ocular imaging modalities such as optical coherence tomography (OCT) and OCT angiography (OCTA) have progressed remarkably. Of these in vivo imaging modalities, recently advanced OCT technology provides high-resolution images, e.g., histologic imaging, enabling anatomical analysis of each retinal layer, including the photoreceptor layers. Recently developed OCTA also visualizes the vascular networks three-dimensionally, which provides better understanding of the retinal deep capillary layer. In addition, ex vivo analysis using autologous aqueous or vitreous humor shows that inflammatory cytokine levels including vascular endothelial growth factor (VEGF) are elevated and correlated with the severity of macular edema (ME) in eyes with retinal vein occlusion (RVO). Furthermore, a combination of multiple modalities enables deeper understanding of the pathology. Regarding therapy, intravitreal injection of anti-VEGF drugs provides rapid resolution of ME and much better visual improvements than conventional treatments in eyes with RVO. Thus, the technologies of examination and treatment for managing eyes with RVO have progressed rapidly. In this paper, we review the multimodal imaging and therapeutic strategies for eyes with RVO with the hope that it provides better understanding of the pathology and leads to the development of new therapies.

In this study, we show augmented autophagy in the retinal pigment epithelial cell line ARPE-19 when cultured in the presence of the lipofuscin pigment A2E. A2E alone does not induce RPE cell death, but cell death was induced in the presence of A2E with the autophagy inhibitor 3-methyladenine (3MA), with a concomitant increase in the generation of mitochondrial reactive oxygen species. On the other hand, the ATP production capacity of mitochondria was decreased in the presence of A2E, and pharmacological inhibition of autophagy had no additional effects. The altered mRNA expression level of mitochondrial function markers was confirmed by real-time polymerase chain reaction, which showed that the antioxidant enzymes SOD1 and SOD2 were not reduced in the presence of A2E alone, but significantly suppressed with the addition of 3MA. Furthermore, transmission electron micrography revealed autophagic vacuole formation in the presence of A2E, and inhibition of autophagy resulted in the accumulation of abnormal mitochondria with loss of cristae. Spheroid culture of human RPE cells demonstrated debris accumulation in the presence of A2E, and this accumulation was accelerated in the presence of 3MA. These results indicate that autophagy in RPE cells is a vital cytoprotective process that prevents the accumulation of damaged cellular molecules.

Shuichiro Hirahara, Yoshio Hirano, Tsutomu Yasukawa, Yuichiro OguraDepartment of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanAbstract: We present a case of retinitis pigmentosa with vitreoretinal traction-associated retinal detachment. The retinal detachment was detected in the nasal periphery. No retinal breaks and no active vascular leakage were observed by fundus scopy and fluorescein angiography, respectively. However, 8 months later, the tractional retinal detachment was spontaneously resolved with posterior vitreous detachment.Keywords: retinitis pigmentosa, vitreoretinal traction, retinal detachment

Yoshio Hirano, Tsutomu Yasukawa, Yuichiro OguraDepartment of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanAbstract: Optical coherence tomography (OCT) has emerged as a powerful diagnostic aid in disorders of the vitreoretinal juncture. The purpose of this study is to determine whether OCT can be used as an additional tool for evaluating an architecture including the thickened area, and the identifiable edge of a macular epiretinal membrane (ERM), and helping us to dissect the ERM from the retinal surface more easily and safely. In two cases with ERM, the edges of the membranes were detected by OCT, and the peeling of the membrane was started at the area easily. OCT guided ERM peeling might be useful for dissecting ERM membranes without any hesitation.Keywords: optical coherence tomography, epiretinal membrane, vitrectomy

Purpose. We report a case of hypertensive choroidopathy with bilateral serous retinal detachments. Patient. A 50-year-old man underwent bilateral serous retinal detachments. Retinal arteriolar narrowing, vascular tortuosity, and arteriovenous nicking were identified in both eyes. The blood pressure was 206/125 mmHg. The patient was diagnosed with bilateral hypertensive choroidopathy and treated with oral antihypertensive treatment. Results and discussion. One month after antihypertensive treatment, the serous retinal detachments resolved and the visual acuity improved. A patient with those findings should be considered as having hypertensive choroidopathy and treated as soon as possible.