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Purpose: To evaluate the efficacy and safety of intravitreal aflibercept (IVT-AFL) versus IVT-AFL plus rescue photodynamic therapy (IVT-AFL + rPDT) in the subgroup of Japanese patients with polypoidal choroidal vasculopathy (PCV) enrolled in the PLANET study., Study Design: A 96-week, double-masked, sham-controlled phase-3b/4 randomized clinical trial conducted at multiple centers from May 2014 to August 2016., Patients and Methods: Patients with PCV (BCVA 73-24 ETDRS letters [20/40-20/320 Snellen]) received 3 initial monthly doses of IVT-AFL 2 mg. At week 12, the patients were randomly assigned 1:1 to IVT-AFL + sham PDT or IVT-AFL + rPDT. Patients not requiring rescue received IVT-AFL every 8 weeks; those requiring rescue received IVT-AFL monthly plus sham/active PDT. Following week 52, the treatment intervals could be extended > 8 weeks., Results: The baseline demographics for the 159 Japanese patients were balanced. At week 96, the mean BCVA change was + 9.7 (IVT-AFL) versus + 9.5 letters (IVT-AFL + rPDT) (least-squares mean difference of - 0.3; 95% CI, - 3.7 to 3.1); the mean central subfield thickness reduction was - 148.0 µm versus - 145.9 µm. Overall, 17.1% of the patients required rescue PDT. At week 96, 25.0% (IVT-AFL) and 37.9% (IVT-AFL + rPDT) of the patients had complete polyp regression; 84.1% (IVT-AFL) and 88.4% (IVT-AFL + rPDT) of the patients had no evidence of active polyps. The mean number of injections (weeks 52-96) were 4.6 (IVT-AFL) and 4.5 (IVT-AFL + rPDT). Overall, 36.0% (IVT-AFL) and 33.8% (IVT-AFL + rPDT) of the patients experienced ocular treatment-emergent adverse events., Conclusion: IVT-AFL monotherapy was efficacious for the treatment of Japanese patients with PCV, and the addition of rescue PDT did not show additional benefits.

Purpose: To describe treatment patterns in patients diagnosed with neovascular age-related macular degeneration (nAMD), retinal vein occlusion (RVO), or diabetic macular edema (DME), newly-treated with anti-vascular endothelial growth factor (anti-VEGF) agents as recorded in the Japanese Medical Data Center (JMDC) database., Study Design: This non-interventional, descriptive, retrospective, observational cohort study included insured Japanese patients aged ≥ 21 and ≤ 75 years at index date (anti-VEGF treatment initiation)., Methods: Patients with minimum one claim in JMDC database with a diagnosis code for nAMD, RVO, or DME between October 2007-May 2015 and with minimum of one claim for anti-VEGF agents on or after the date of diagnosis were included. Frequency and proportion of claims submitted for anti-VEGF injections were assessed during 12 months post-index date., Results: The median (interquartile range) number of claims for anti-VEGF injections during 12 months post-index date were 3 (1, 4) for nAMD (n = 255), 2 (1, 3) for RVO (n = 223) and 2 (1, 4) for DME (n = 125) patients. Frequencies of nAMD, RVO and DME patients with one or more claims for a retinal disease treatment other than an anti-VEGF agent were 4 (1.57%), 59 (26.46%) and 68 (54.40%) during the 12 months pre-index date and 21 (8.24%), 85 (38.12%) and 62 (49.60%) in the 12 months post-index date, respectively., Conclusions: The median number of anti-VEGF injections per patient was lower than those reported in clinical trials. Although various pre- and concomitant treatments were used in RVO and DME, anti-VEGF monotherapy was the first-line treatment in > 90% of nAMD patients.

In the original publication, under section, BRVO treatment practice pattern, the sentence in p. 369 was published as.

Purpose: To elucidate the current clinical practice patterns of branch retinal vein occlusion (BRVO) management by retina specialists in Japan in the era of anti-vascular endothelial growth factor (VEGF) therapy., Study Design: A voting survey using an answer pad system., Methods: On May 28, 2017, forty-one retina specialists were surveyed on the pathology and clinical practice of BRVO management., Results: Most specialists (77.5%) use fundus examination and optical coherence tomography (OCT) for diagnosis of macular edema (ME) secondary to BRVO. All assess the condition of the ellipsoid zone (EZ) and external limiting membrane (ELM) and consider this a visual prognostic factor. For ME secondary to BRVO, anti-VEGF therapy is the first choice, and most specialists (82.4%) select initial injection followed by a pro re nata (PRN) regimen. For switching to other treatment options for persistent cases, combination therapy of anti-VEGF injections and laser therapy is the most common choice (35.9%), whereas 25.6% select vitreous surgery and 15.4% select adding steroid injections., Conclusions: Our survey presents the current opinions on the diagnosis and treatment of BRVO by retina specialists in Japan, and reveals the common views about damage to the EZ/ELM as a factor of poor prognosis and anti-VEGF therapy as the first line treatment, highlighting various opinions on initiation and switching of therapy.

Purpose: To evaluate the efficacy of indocyanine-green angiography (ICGA)-guided navigated focal laser photocoagulation for diabetic macular edema (DME)., Study Design: Prospective, interventional case series., Methods: Six patients (8 eyes) were enrolled in this study. Fluorescein angiography (FA) and ICGA were performed using the Heidelberg Retina Angiogram 2 (Heidelberg Engineering). Navigated focal laser photocoagulation was delivered to the microaneurysms on ICGA using Navilas ® (OD-OS GmbH, Germany). Central retinal thickness (CRT) and macular volume (MV) were measured by Cirrus HD-OCT (Carl Zeiss Meditec). At 6 months, the best-corrected visual acuity (BCVA), CRT and MV were compared to the values measured on day 0. The distances from the center of fovea to the closest microaneurysms (MAs) were measured on the pre-planned Navilas ® image., Results: All eyes had previous treatment history. At 6 months, ICGA-guided navigated focal laser photocoagulation significantly reduced the CRT and the MV (p<0.05), and there was improvement in the BCVA (p<0.05). At 3 months, 5 out of the 8 eyes (63%) underwent additional ICGA-guided navigated focal laser photocoagulation due to remnants of MAs that had been confirmed by ICGA. There was no observed recurrence of edema after the ICGA-guided navigated focal laser photocoagulation during the 6-month follow-up. The mean distance from the center of fovea to the closest MAs was 624.8 ± 377.7 μm (range 336.0-1438.9 μm)., Conclusion: Our data suggest ICGA-guided navigated focal laser photocoagulation may be effective for the treatment of DME.

Purpose: To investigate the visual impairment certification status in Japan., Study Design: Observational cross-sectional study., Methods: We asked all welfare offices throughout Japan to submit data concerning age, sex, causative diseases, and visual impairment grades for newly certified visually impaired individuals aged ≥ 18 years in the fiscal year of 2015. The certification was based on criteria of the Act on Welfare of Physically Disabled Persons., Results: In total, data were collected for 12,505 newly certified visually impaired individuals. The most common age group for these individuals was 80-89 years (29.6%), followed by 70-79 (26.3%) and 60-69 (17.3%) years. The most common causative disease was glaucoma (28.6%), followed by retinitis pigmentosa (14.0%), diabetic retinopathy (12.8%), and macular degeneration (8.0%). Glaucoma was the most common causative disease in both sexes (30.2% in men and 27.0% in women). The most common impairment grade was grade 2 (31.8%), followed by grades 5 (24.3%) and grade 1 (16.1%). The number of visually impaired individuals with underlying glaucoma had increased in comparison with the number in the most recent surveys (from fiscal years 2007 to 2009), whereas the number of individuals with underlying diabetic retinopathy and macular degeneration had decreased., Conclusion: To our knowledge, this is the first nation-wide complete enumeration survey of newly certified visually impaired individuals in Japan. These findings may contribute to administrative activities concerning medical welfare as well as educational activities for preventing visual impairment.

Diabetic retinopathy is a frequent cause of visual impairment in working-age adults (≥ 30 years) and in Japan is most commonly observed in those aged 50-69 years. Diabetic macular edema (DME) is one of the main causes of vision disturbance in diabetic retinopathy, which is a clinically significant microvascular complication of diabetes. Anti-vascular endothelial growth factor (VEGF) therapy is becoming the mainstay of treatment for DME. However, to achieve sustained long-term improvement in visual acuity, conventional laser photocoagulation, vitrectomy and steroid therapy are also expected to play a role in the treatment of DME. This review summarizes the epidemiology and pathology of diabetic retinopathy and DME, evaluates the findings regarding the diagnosis and treatment of DME, and underscores the importance of systemic management of the disease in the context of the current health care situation in Japan. Finally, the unmet needs of patients with DME and prospects for research are discussed. The weight of evidence suggests that it is important to establish a multipronged treatment strategy centered on anti-VEGF therapy.

Purpose: To elucidate the current clinical practice patterns of diabetic macular edema (DME) management by retinal specialists in Japan in the era of anti-vascular endothelial growth factor (VEGF) therapy., Methods: Forty-six retinal specialists were administered a survey regarding the pathology and clinical practice of DME., Results: Nearly, half of the specialists (45.2 %) think that the main biochemical factor involved in DME development is the vascular permeability-potentiating action of VEGF-A. Most specialists (70.6 %) use three modalities for detecting DME: optical coherence tomography, fluorescein angiography, and fundus examination. For focal macular edema, focal laser is used as first-line therapy by 70.3 % of specialists, whereas 21.6 % use medical treatment in combination with focal/grid laser. For diffuse macular edema, anti-VEGF therapy is the first choice (72.5 %), irrespective of visual acuity, whereas 17.5 % select off-label sub-Tenon's steroid injections. Vitrectomy is often performed for vitreomacular traction (86.5 %) or when anti-VEGF agent/laser therapy is ineffective (73.2 %). For persistent DME after vitrectomy, anti-VEGF agents (46.3 %) or steroids (intravitreal injections, 14.6 %; sub-Tenon's injections, 36.6 %) are selected. When applying anti-VEGF treatment regimen, most specialists continue loading injections until central retinal thickness stabilized (51.4 %) or both visual acuity and central retinal thickness stabilized (24.3 %). In the maintenance phase, many specialists provide injections with pro re nata (76.3 %), whereas 50.0 % responded that the treat-and-extend regimen is ideal., Conclusions: Our survey presents the current views about the DME management and practice patterns of anti-VEGF therapy by one part of the retinal specialists in Japan, and highlights the differences or gaps between evidence and actual clinical practice.

Purpose: Fibrovascular scar formation related to subfoveal type 2 choroidal neovascularization (CNV) often causes severe vision loss in eyes with age-related macular degeneration. The authors assessed additional impacts of intravitreal tissue plasminogen activator (tPA), a fibrinolytic compound, combined with intravitreal ranibizumab (IVR) on subfoveal type 2 CNV., Methods: Eight eyes of eight patients with type 2 CNV underwent intravitreal injections of ranibizumab and tPA (IVR/tPA) (40 kIU). Twelve eyes of 12 patients with type 2 CNV were treated with only IVR injections, as the control group. For retreatment, IVR was performed as needed. The best-corrected visual acuity (BCVA) and the central retinal thickness (CRT) and macular volume (MV) on optical coherence tomography were recorded periodically for 6 months., Results: The subretinal fibrinous and fibrovascular tissue complex regressed or contracted immediately after administration of IVR/tPA in contrast to IVR monotherapy. The total numbers of IVR injections did not differ significantly between the two groups. The mean logarithm of the minimum angle of resolution BCVA in the combination therapy group improved significantly from 0.72 at baseline to 0.51 at month 6 and was superior to that in the monotherapy group (0.70-0.79). The improvements of the mean CRT and MV in the combination therapy group were superior to the monotherapy group. No tPA-related complications developed., Conclusions: tPA may have a specific ability to regress already formed subretinal fibrinous and fibrovascular tissue complexes in eyes with type 2 CNV, potentially increasing the chances of visual improvement through a synergistic relationship with anti-VEGF therapies.

Background: Retinal ischemia in eyes with diabetic retinopathy and retinal vein occlusion leads to local tissue acidosis. Acid-sensing ion channels (ASICs) are expressed in photoreceptors and other neurons in the retina, and may play a role in acid-induced cell injury. The purpose of this study was to investigate the neuroprotective effects of amiloride, an ASIC blocker, on induced retinal ischemia in rats., Methods: Transient retinal ischemia was induced in male Long-Evans rats by the temporary ligation of the optic nerve. Just before the induction of ischemia, the experimental eyes underwent intravitreal injection of amiloride. On day 7, the retinal damage in eyes that underwent amiloride treatment (and in those that did not undergo the treatment) was evaluated by histology and electroretinogram (ERG)., Results: Transient retinal ischemia caused retinal degeneration with thinning of the inner layer of the retina. The blockage of ASICs with amiloride significantly prevented retinal degeneration. ERG demonstrated that the reduction in a- and b-wave amplitudes induced by the transient retinal ischemia was significantly prevented by the application of amiloride., Conclusions: The present study suggests that ASICs might, at least in part, play a pathophysiological role in ischemia-induced neurodegeneration. Blockage of ASICs may have a potential neuroprotective effect in ocular ischemic diseases.

Background: We report a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and the associated spatio-temporal pathologic findings of this disease., Patients: A 29-year-old woman with bilateral recurrent APMPPE., Observations: The patient complained of bilateral blurred vision. The best-corrected visual acuity was 20/13 bilaterally. Slit-lamp examination revealed bilateral, multiple, yellowish-white, flat, placoid lesions over the posterior fundus. A hyperreflective area between the outer nuclear layer (ONL), and the photoreceptor inner and outer segments (IS/OS) visible on the optical coherence tomographic images and a hyperfluorescent area identified on the late-phase fluorescein angiographic images were spatio-temporally consistent with the presence of the placoid lesions. The pattern of juxtafoveal hyperfluorescent spots was accompanied by multiple hypofluorescent, wedge-shaped lesions. The hypofluorescent lesions visible on the indocyanine green angiographic (ICGA) images were irregular in shape and intensity. APMPPE was diagnosed, and the patient was treated with an initial 30 mg dose of oral prednisolone, followed by a 3-week taper. The lesions recurred in an area where hypofluorescent lesions had not occurred previously, while the previous hypofluorescent spots resolved completely without the hyperfluorescence associated with vascular remodeling., Conclusions: These findings suggest that the placoid appearance of APMPPE may correspond to edema between the ONL and the photoreceptor IS/OS and that the hypofluorescent lesions characteristic of this condition visible on ICGA images might reflect infiltration and subsequent blockage of choroidal vasculature-derived fluorescence.

Purpose: To evaluate the incidence and risk factors of intraocular pressure (IOP) elevation following triamcinolone acetonide (TA) administration., Methods: In this retrospective observational case series, patients (224 eyes of 202 patients) with diffuse diabetic macular edema (66 eyes), branch retinal vein occlusion (39 eyes), central retinal vein occlusion (25 eyes), exudative age-related macular degeneration (49 eyes), myopic choroidal neovascularization (10 eyes), uveitis (30 eyes), or other conditions (5 eyes) were administered an intravitreal or posterior sub-Tenon capsule injection, or both, of TA. Sub-Tenon capsule injection was performed on 106 eyes (STTA group). Intravitreal injection was performed on 118 eyes (IVTA group), of which 85 eyes underwent simultaneous intravitreal and sub-Tenon capsule injections. Mean follow-up after TA administration was 15.9 +/- 10.4 (range, 3-39) months. The sub-Tenon capsule injection and intravitreal injection of TA were compared with respect to the frequency of IOP elevation and the time between TA administration and the initial IOP elevation, and the possible risk factors responsible for IOP elevation were identified., Results: There was no significant difference in frequency of IOP > 21 mmHg between the STTA group and the IVTA group (P = 0.0588). There was, however, a significant difference in the frequency of IOP > 30 mmHg between the two groups (P = 0.0004). In the IVTA group, more patients needed antiglaucoma medication than in the STTA group (P = 0.0052). The incidence rate of IOP elevation within 1 week after TA administration in the IVTA group was significantly higher than in the STTA group (P = 0.0154). Risk factors for IOP elevation included higher baseline IOP (P < 0.0001), younger patients (P = 0.0095), and simultaneous administration of sub-Tenon capsule and intravitreal injections (P = 0.0228)., Conclusions: Careful follow-up of IOP is required after TA injections.

Purpose: To evaluate dye retention in the fundus after indocyanine green (ICG)-assisted internal limiting membrane peeling., Methods: Ten eyes with stage 3 or 4 nondiabetic idiopathic macular hole (MH group) and six eyes with diffuse diabetic macular edema (DM group) were studied. The fundus was examined with 780-nm infrared illumination by a scanning laser ophthalmoscope (SLO) after ICG-assisted internal limiting membrane peeling. The postoperative follow-up period ranged from 6 to 12 months (mean+/-SD, 3.7+/-2.6 months)., Results: Fluorescence from ICG was detected in all studied eyes in both groups up to 6 months after surgery. At 9 months after surgery, ICG fluorescence was visible in all eyes of the DM group, but in only one-third of eyes of the MH group. No fluorescence was detected in fellow eyes that had not been operated on., Conclusion: The present study using SLO revealed that ICG remains in the fundus for over 6 months after surgery. The results also suggested that a longer time might be required for dye clearance from the diabetic retina than from the nondiabetic retina., (Copyright (c) Japanese Ophthalmological Society 2006.)

The objective was to describe a new surgical technique to manage a posteriorly dislocated crystalline lens. Four patients with posteriorly dislocated lenses were studied. Two patients had dislocated lenses secondary to trauma, 1 had undergone retinal detachment surgery, and 1 had an idiopathic lens dislocation. Pars plana vitrectomy was carried out on all 4 eyes, followed by an injection of perfluoro-n-octane to float the lens off the retina. The lens was phacoemulsified through a limbal incision, and an intraocular lens was positioned in the ciliary sulcus with suture fixation. Perfluoro-n-octane was replaced by a balanced salt solution. Postoperative visual acuity ranged from 1.0-1.5. Transient choroidal detachment and hypotony were observed in 3 eyes in the early postoperative period. Postoperative ocular hypertension was noted in 2 eyes and was well-controlled with topical antiglaucoma agent. These results indicate that limbal lensectomy of a posteriorly dislocated lens using perfluorocarbon liquids is a beneficial and relatively safe method.

Although cataract extraction with intraocular lens implantation (IOL) is being used for increasing numbers of patients, there is still insufficient information regarding the long-term outcome for these patients. In this retrospective study of 140 eyes of 102 patients, 97 eyes (69%) achieved a best visual acuity of 20/40 or better. After a minimum 6-month postoperative period, 26 eyes (19%) had developed retinopathy: eight eyes progressed from nonproliferative to proliferative retinopathy. Glycosylated hemoglobin levels and fasting blood glucose were significantly higher at time of surgery in the eight that progressed than in those who did not (P = 0.002, P = 0.034). There were 65 unilateral IOL implantations; in 10 (15%) of these eyes, retinopathy progressed. Retinopathy also progressed in 70% of the fellow eyes of these patients. In patients whose retinopathy did not progress, 95% of the fellow eyes also showed no progression. Also, patients with progression in the pseudophakic eye frequently had progression in the fellow unoperated eye. Postoperative progression was symmetrical (P = 0.0001). Our analysis suggests that progression of diabetic retinopathy following IOL implantation can be correlated to diabetic control at the time of surgery.