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Purpose: Review and provide consensus recommendations on use of treat-and-extend (T&E) regimens for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) management with relevance for clinicians in the Asia-Pacific region., Methods: A systematic search of MEDLINE, EMBASE, and Cochrane databases, and abstract databases of the Asia-Pacific Vitreo-retina Society, European Society of Retina Specialists, American Academy of Ophthalmology, and Controversies in Ophthalmology: Asia-Australia congresses, was conducted to assess evidence for T&E regimens in nAMD. Only studies with ≥100 study eyes were included. An expert panel reviewed the results and key factors potentially influencing the use of T&E regimens in nAMD and PCV, and subsequently formed consensus recommendations for their application in the Asia-Pacific region., Results: Twenty-seven studies were included. Studies demonstrated that T&E regimens with aflibercept, ranibizumab, or bevacizumab in nAMD, and with aflibercept in PCV, were efficacious and safe. The recommendation for T&E is, after ≥3 consecutive monthly loading doses, treatment intervals can be extended by 2 to 4 weeks up to 12 to 16 weeks. When disease activity recurs, the recommendation is to reinject and shorten intervals by 2 to 4 weeks until fluid resolution, after which treatment intervals can again be extended. Intraretinal fluid should be treated until resolved; however, persistent minimal subretinal fluid after consecutive treatments may be tolerated with treatment intervals maintained or extended if the clinical condition is stable., Conclusions: T&E regimens are efficacious and safe for nAMD and PCV, can reduce the number of visits, and minimize the overall burden for clinicians and patients., Competing Interests: Conflicts of interest: VC: honoraria from Bayer, Novartis, Roche for lecture fees and research grants from Bayer, Roche; MS: honoraria from Allergan, Bayer, Novartis, Roche for lecture fees, consultancy and board membership, research grants from Allergan, Bayer, Novartis; TL: honoraria from Allergan, Bayer, Boehringer Ingelheim, Novartis, Roche for consultancy, research grants from Novartis and Roche; GT: honoraria from Allergan, Bayer, Roche, Novartis, Topcon, and research grant from Leica and Santen; NF: honoraria from Bayer, Novartis, and Allergan for lecture fees; MO: honoraria from Bayer, Novartis, Santen, Kowa, Otsuka for lecture fees, research grants from Alcon, Bayer, Hoya, Novartis, Otsuka, Santen, Senju, and consultancy fees from Allergan, Bayer, Chengdu Kanghong Biotechnology, Chugai, Novartis; PM: N/A;, (Copyright © 2021 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

Intravitreal injections of vancomycin (VCM) and ceftazidime (CAZ) are commonly used to treat infectious endophthalmitis. When patient cases require retinal detachment with silicone oil (SO) tamponade, the antibiotic doses are empirically reduced to 25 %. Currently, there is no scientific evidence for these empirical dose reductions. The purpose of the present study is to determine the quantitative impact that SO tamponades have on intraocular VCM pharmacokinetics. Because of high invasiveness of frequent sampling of intraocular VCM concentrations in human, this pharmacokinetic study was performed in cynomolgus monkey's eyes. Population pharmacokinetic modeling and simulation were performed using 75 different intraocular VCM concentrations obtained from 8 male cynomolgus monkeys. A one-compartment model with a first-order diffusion rate was used as a structural pharmacokinetic model. From the covariate analysis, SO tamponade significantly decreased the volume of distribution while pars plana vitrectomy with lensectomy (PPV) significantly increased the clearance and diffusion rate constants. From the Monte Carlo simulation (n = 1,000), the median time above minimum inhibitory concentration (T >MIC , a therapeutic effect index) durations of SO and normal eyes at clinical doses of 1,000 µg were 2.6 and 11.0 days, respectively. Using intravitreal injections of VCM with SO tamponade or PPV may reduce the therapeutic effect., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To investigate acquired color vision deficiency (CVD) using the Rabin cone contrast test (RCCT) in patients with retinal vein occlusion (RVO)., Methods: We retrospectively evaluated 39 patients with macular edema due to RVO who were treated with intravitreal injections of anti-VEGF agents and demonstrated improvement of best-corrected visual acuity to 20/20 Snellen VA or better. The acquired CVD was evaluated by the RCCT and standard pseudo-isochromatic plates-part 2 (SPP-2)., Results: Mean L, M, and S color contrast test (CCT) scores were significantly lower in RVO eyes than in the fellow eyes (L CCTs, 70.0 ± 13.3 vs. 90.0 ± 8.0, respectively, P < 0.01; M CCTs, 85.0 ± 16.6 vs. 95.0 ± 5.7, respectively, P < 0.01; S CCTs, 80.0 ± 21.5 vs. 95.0 ± 7.1, respectively, P < 0.01). Acquired CVD was diagnosed in 25 eyes of 39 patients by the RCCT and in 15 eyes of 39 patients by SPP-2. The RCCT was performed on two different days in 21 patients. It revealed acquired CVD in 17 eyes on the first day and in 10 eyes on the second day. Acquired CVD was improved in 9 eyes, unchanged in 8 eyes, and worsened in 2 eyes., Conclusions: The RCCT revealed eyes with RVO had acquired CVD. Acquired CVD caused by RVO can be improved further in some cases even after recovery of vision to 20/20. The RCCT may be able to quantitatively diagnose acquired CVD status., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To evaluate systemic adverse events after screening for retinopathy of prematurity (ROP) performed with mydriatic., Methods: This was a retrospective case series study. Medical records of consecutive patients who underwent screening for ROP with 0.5% phenylephrine and 0.5% tropicamide eyedrops were retrospectively reviewed. The score of abdominal distention (0-5), volume of milk sucked and volume of stool, along with systemic details (pulse and respiration rates, blood pressure and number of periods of apnea) were collected at 1 week and 1 day before ROP examination, and at 1 day after examination. Results were compared between the days before and after examination. Correlation between body weight at the time of examination and the score of abdominal distention was examined. The numbers of infants with abdominal and/or systemic adverse events were compared between pre- and post-examination periods., Results: Eighty-six infants met the inclusion criteria. The score of abdominal distention increased from 2.0 at 1 day before examination to 2.3 at 1 day after examination (p = 0.005), and the number of infants who had worsened abdominal distension increased after examination (p = 0.01). Infants with lower body weight had a higher score of abdominal distention (p < 0.0001, r = -0.57). The number of infants with reduced milk consumption increased after examination (p = 0.0001), as did the number of infants with decreased pulse rate (p = 0.0008)., Conclusions: Screening for ROP with mydriatic may have adverse effects on systemic conditions. Infants should be carefully monitored after ROP screening with mydriatic., Competing Interests: M.O. reports personal fees from Santen Pharmaceutical, unrelated to the submitted work. We used Midorin-PTM eye drop marketed by Santen Pharmaceutical, a mixture of 0.5% phenylephrine and 0.5% tropicamide, as mydriatics which is commonly used in Japan. The other authors declare that they have no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: To investigate the effects of internal limiting membrane (ILM) peeling on visual acuity (VA) after rhegmatogenous retinal detachment (RRD) surgery., Methods: This retrospective analysis examined the medical records of patients with RRD who underwent vitrectomy at 26 institutions. To detect prognostic factors of VA at 6 months postoperatively (post-VA), multivariate linear regression was performed with post-VA as the objective variable; ILM peeling, sex, age, preoperative VA (pre-VA), intraocular pressure, axial length, duration of RRD, and cataract surgery served as explanatory variables. Recurrence of RRD and epiretinal membrane formation within 6 months postoperatively were compared between groups of patients with and without ILM peeling, among patients with macula-on and macula-off RRD., Results: The inclusion criteria were met by 523 eyes with a macula-on RRD and 364 eyes with a macula-off RRD. ILM peeling was performed in 85 eyes with a macula-on RRD and 57 eyes with a macula-off RRD. In eyes with a macula-on RRD, ILM peeling did not affect post-VA (p = 0.72). Vitrectomy without cataract surgery and poor pre-VA were significantly associated with poor post-VA (p = 0.01 and p < 0.001, respectively). In eyes with a macula-off RRD, ILM peeling, long duration of RRD, and poor pre-VA were significantly associated with poor post-VA (p = 0.037, p = 0.007, and p < 0.001, respectively). Recurrence of RRD and epiretinal membrane formation were similar between groups of patients with and without ILM peeling, among patients with macula-on and macula-off RRD. Retina sensitivity was not evaluated by microperimetry., Conclusion: ILM peeling did not affect post-VA in eyes with a macula-on RRD, whereas post-VA was worse in eyes with ILM peeling than in eyes without peeling, among eyes with a macula-off RRD., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To report the 2-year efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) compared with monthly ranibizumab in patients with treatment-naïve neovascular age-related macular degeneration (nAMD)., Design: Two multicenter, randomized, phase 3 clinical trials with identical protocols (CEDAR and SEQUOIA). Analyses used pooled trial data., Participants: The trials enrolled 1888 patients (1 eye/patient) with active choroidal neovascularization secondary to age-related macular degeneration and best-corrected visual acuity (BCVA) of 24 to 73 Early Treatment Diabetic Retinopathy Study letters., Methods: At enrollment, patients were assigned to study eye treatment with abicipar 2 mg every 8 weeks after initial doses at baseline and weeks 4 and 8 (abicipar Q8, n = 630), abicipar 2 mg every 12 weeks after initial doses at baseline and weeks 4 and 12 (abicipar Q12, n = 628), or ranibizumab 0.5 mg every 4 weeks (ranibizumab Q4, n = 630)., Main Outcome Measures: Efficacy measures included stable vision (<15-letter loss in BCVA from baseline) and change from baseline in BCVA and central retinal thickness (CRT). Safety measures included adverse events (AEs)., Results: For patients who completed the study, efficacy of abicipar after initial doses was maintained through week 104. At week 104, the proportion of patients with stable vision was 93.0% (396/426), 89.8% (379/422), and 94.4% (470/498); mean change in BCVA from baseline was +7.8 letters, +6.1 letters, and +8.5 letters, and mean change in CRT from baseline was -147 μm, -146 μm, and -142 μm in the abicipar Q8 (14 injections), abicipar Q12 (10 injections), and ranibizumab Q4 (25 injections) groups, respectively. The overall incidence of intraocular inflammation (IOI) AEs was 15.4%, 15.3%, and 0.3% from baseline through week 52 and 16.2%, 17.6%, and 1.3% from baseline through week 104 in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively., Conclusions: Two-year results show efficacy of abicipar Q8 and Q12 in nAMD. First onset of IOI events with abicipar was much reduced in the second year and comparable with ranibizumab (0.8% and 2.3% vs. 1.0%). The extended duration of effect of abicipar allows for quarterly dosing and reduced treatment burden., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: We investigated 10-year changes in baseline best-corrected visual acuity (BCVA), as well as functional and anatomical changes at 1 and 2 years after initial treatment, in eyes with treatment-naïve neovascular age-related macular degeneration (nAMD)., Methods: This retrospective, multicenter, case series reviewed patients with treatment-naïve nAMD who underwent initial treatment from 2006 to 2015, using photodynamic therapy (PDT), anti-vascular endothelial growth factor (VEGF), or a combination of PDT and anti-VEGF. BCVA and central retinal subfield thickness (CRST), were measured at baseline and at 1 or 2 years of follow-up., Results: In total, 3096 eyes of 3096 patients were included from 14 hospitals. Mean BCVA at baseline became significantly better over the 10-year study period (P < 0.001). BCVA at 1 year significantly improved from baseline in patients who underwent initial treatment from 2009 to 2015 (P = 0.001, 2009; P = 0.004, 2010; P = 0.01, 2011; P < 0.001, 2012-2015). BCVA at 2 years significantly improved from baseline in patients who underwent initial treatment from 2012 to 2015 (P < 0.001, 2012; P < 0.001, 2013-2015). CRST at 1 year decreased significantly from CRST at baseline, each year from 2006 to 2015 (P < 0.001, 2006-2015). CRST at 2 years decreased significantly from CRST at baseline, each year from 2006 to 2015 (P = 0.03, 2006; P < 0.001, 2007-2015)., Conclusion: Baseline BCVA with treatment-naïve nAMD tended to become better during the study period. BCVA at 1 year improved in the era of anti-VEGF; BCVA at 2 years improved in patients who underwent initial treatment in 2012 or later; and CRST decreased in each year during the study period.

Bacterial endophthalmitis is an intraocular infection that causes rapid vison loss. Pathogens can infect the intraocular space directly (exogenous endophthalmitis (ExE)) or indirectly (endogenous endophthalmitis (EnE)). To identify predictive factors for the visual prognosis of Japanese patients with bacterial endophthalmitis, we retrospectively examined the bacterial endophthalmitis characteristics of 314 Japanese patients and performed statistics using these clinical data. Older patients, with significantly more severe clinical symptoms, were prevalent in the ExE group compared with the EnE group. However, the final best-corrected visual acuity (BCVA) was not significantly different between the ExE and EnE groups. Bacteria isolated from patients were not associated with age, sex, or presence of eye symptoms. Genus Streptococcus , Streptococcus pneumoniae, and Enterococcus were more prevalent in ExE patients than EnE patients and contributed to poor final BCVA. The presence of eye pain, bacterial identification, and poor BCVA at baseline were risk factors for final visual impairment.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness and intravitreal anti-vascular endothelial growth factor (VEGF) injection is becoming a first-line choice for treatment of ROP. However, there is a major concern that intravitreally injected anti-VEGF agents could escape from the eye into the systemic circulation and impair systemic development. Moreover, escaped anti-VEGF agents could have an effect on the retina of the fellow eye. In this study, we investigated the hematogenous effect of a single intravitreal anti-VEGF injection in a mouse model of ROP. Here, we showed that single intravitreal aflibercept injection to one eye can affect body weight gain, the fellow eye, and renal vessels, although no apparent effect was observed in brain vessels. Furthermore, this hematogenous effect was dose-dependent. Our results provide very important insights into the clinical use of anti-VEGF agents for ROP treatment., (© 2021 Federation of American Societies for Experimental Biology.)

Purpose: This study evaluated the pharmacokinetics of intravitreal vancomycin and ceftazidime in the aqueous humor of macaque eyes filled with silicone oil in the vitreous cavity., Methods: Intravitreal vancomycin (1 mg/0.1 mL) and ceftazidime (2 mg/0.1 mL) were injected into four normal macaque eyes, four vitrectomized aphakic macaque eyes, and four previously vitrectomized aphakic macaque eyes filled with silicone oil (silicone oil-filled eyes). Aqueous humor samples (0.1 mL) were obtained just before injection and at 2 and 5 hours and 1, 2, 3, 5, 7, and 10 days after injection. In each group, corneal endothelial cell density (ECD) measurements and electroretinogram (ERG) recordings were obtained before injection and after 1 month., Results: The half-lives of vancomycin in the aqueous humor of normal, vitrectomized, and silicone oil-filled eyes were 29.4, 21.1, and 6.8 hours, respectively, and those of ceftazidime were 20.4, 5.2, and 3.1 hours, respectively. The maximum vancomycin aqueous humor concentrations of normal, vitrectomized, and silicone oil-filled eyes were 151.4, 205.6, and 543.5 µg/mL, respectively, and the maximum ceftazidime aqueous humor concentrations are 64.6, 260.0, and 1176.3 µg/mL, respectively. There was no change in ECD, and ERG was not declined after intravitreal injection in all groups., Conclusions: The half-lives of vancomycin and ceftazidime in the aqueous humor were shorter in silicone oil-filled eyes than in normal and vitrectomized eyes. High antibiotic concentrations in silicone oil-filled eyes seemed to be well tolerated., Translational Relevance: This study aids in estimating how often an antibiotic should be intravitreally injected for endophthalmitis of silicone oil-filled eyes.

Purpose: To determine the characteristics of fundus autofluorescence (FAF) images and visual functions in eyes with Stickler syndrome using ultra-widefield FAF images., Methods: Forty-six eyes of 26 patients with mutations in the COL2A1 gene underwent ultra-widefield FAF imaging. The eyes were categorized into three types; no signs of abnormal AF, predominantly hyperfluorescent AF (hyper-AF), and predominantly hypofluorescent AF (hypo-AF). Goldmann perimetry was performed on 34 eyes, and line-scan images of the abnormal AF lesions were obtained by swept-source optical coherence tomography in 4 eyes., Results: Abnormal AF lesions were found in 37 eyes of 21 (80.7%) of the 26 patients. Hyper-AF was found in 15 eyes and hypo-AF was found in 22 eyes. The FAF changes corresponded with the funduscopically observed radial paravascular retinal degeneration. The average age at the examination was significantly younger in patients who had eyes with hyper-AF or no abnormal AF than in those with hypo-AF (12.8 vs. 28.4 years; P = 0.009). Abnormal AF-associated visual field defects were found in 5/10 (50%) eyes with hyper-AF and 17/18 (94%) eyes with hypo-AF. Hyper-AF changes tended to appear before retinal changes were detectable by fluorescein angiography. An absence of the ellipsoid zone and the outer nuclear layer and a thinning of the overall retinal thickness were found corresponding to the hypo-AF lesions in the swept source optical coherence tomography images., Conclusion: Abnormal FAF is characteristic of eyes with Stickler syndrome. Age-related alterations of the FAF was associated with visual field defects and disruption of the photoreceptors and retinal pigment epithelial cells., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: The aim of the current study was to investigate the correlation between the pretreatment aqueous level of vascular endothelial growth factor (VEGF) and clinical activity in neovascular age-related macular degeneration., Methods: Patients with neovascular age-related macular degeneration treated by intravitreal ranibizumab injections and followed for 12 months were included in the current study. The treatment regimen consisted of three consecutive monthly intravitreal ranibizumab injections (loading treatment) followed by a pro re nata (PRN) treatment regimen. The aqueous VEGF levels were measured by enzyme-linked immunosorbent assay using aqueous humor samples obtained just before the first intravitreal ranibizumab injections., Results: Sixty-four eyes of 64 patients were included in the current study. The mean number of intravitreal ranibizumab injections during 12 months was 4.6 ± 1.4, and 17 eyes had no recurrence after loading treatment. The mean aqueous VEGF level was significantly higher in eyes with recurrence after loading treatment than in eyes without recurrence (107.6 vs. 83.8 pg/mL, respectively; P = 0.04) and significantly higher in eyes with recurrence within 3 months after loading treatment than in other eyes (114.9 vs. 86.7 pg/mL, respectively; P < 0.01)., Conclusion: Pretreatment aqueous VEGF level was significantly correlated with the likelihood of recurrence in neovascular age-related macular degeneration. The measurement of pretreatment aqueous VEGF level may be useful to determine the best treatment options for patients with neovascular age-related macular degeneration.

Purpose: To compare the efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) versus ranibizumab every 4 weeks in treatment-naïve patients with neovascular age-related macular degeneration (AMD)., Design: Two randomized, multicenter, double-masked, parallel-group, active-controlled, phase 3 clinical trials (CEDAR, SEQUOIA) with identical protocols were conducted. Data from both trials were pooled for analysis., Participants: Patients with active choroidal neovascularization secondary to AMD and best-corrected visual acuity (BCVA) of 24-73 Early Treatment Diabetic Retinopathy Study letters in the study eye were enrolled., Methods: Patients (n = 1888) were randomized in a 1:1:1 ratio to study eye treatment with abicipar 2 mg every 8 weeks after 3 initial doses at baseline and weeks 4 and 8 (Q8), abicipar 2 mg every 12 weeks after 3 initial doses at baseline and weeks 4 and 12 (Q12), or ranibizumab 0.5 mg every 4 weeks (Q4)., Main Outcome Measures: The primary efficacy end point was proportion of patients with stable vision (defined as <15-letter loss in BCVA from baseline) in the study eye at week 52. Secondary end points included change from baseline in BCVA and central retinal thickness (CRT) at week 52. Safety measures included adverse events (AEs)., Results: The proportion of patients with stable vision at week 52 was 93.2%, 91.3%, and 95.8% in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively, with both abicipar Q8 and Q12 noninferior to ranibizumab Q4. Week 52 mean change from baseline in BCVA was 7.5, 6.4, and 8.4 letters and in CRT was -144, -145, and -144 μm in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively. Incidence of intraocular inflammation (IOI) AEs was 15.4%, 15.3%, and 0.3%, respectively. The IOI AEs were typically mild or moderate in severity and treated with topical corticosteroids; 62 of 192 patients (32.3%) received oral and/or injectable corticosteroids., Conclusions: Abicipar Q8 and Q12 were both noninferior to ranibizumab Q4 in the primary end point of stable vision at week 52. Intraocular inflammation was more frequent with abicipar. Quarterly and Q8 abicipar reduce nAMD disease and treatment burden compared with monthly treatment., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: To evaluate the safety and efficacy of BBG (Brilliant Blue G250) for lens capsular staining during cataract surgery with continuous curvilinear capsulorhexis., Study Design: Prospective clinical study., Methods: This clinical trial enrolled 30 eyes of 30 patients who underwent cataract surgery with BBG (0.25 mg/mL Brilliant Blue G250) for capsular staining. Visualization of the lens capsule and the ease of capsulorhexis with BBG staining were evaluated in five grades (grade 0 to 4) by the Independent Data Monitoring Committee and the surgeons. The safety of BBG was also evaluated in terms of ocular and systemic tolerance for 7 days after surgery., Results: The use of BBG improved visualization of the lens capsule and complete capsulorhexis was performed in all patients. The major endpoint (Independent Data Monitoring Committee evaluation) showed that use of BBG improved visualization of the lens capsule and the ease of capsulorhexis (grades 2 to 4); the committee's grading results were similar to those of the surgeons. Frequent complications observed in more than two eyes were conjunctival injection, corneal edema and intraocular pressure elevation. No severe complications were observed in ocular and systemic evaluations., Conclusion: BBG staining contributed to improved visualization of the lens capsule and aided in the completion of capsulorhexis during cataract surgery. The use of BBG for capsular staining also exhibited favorable safety results.

Purpose: To evaluate the effectiveness, safety, and treatment patterns of ranibizumab 0.5 mg in treatment-naive patients with neovascular age-related macular degeneration enrolled in LUMINOUS study., Methods: This 5-year, prospective, multicenter, observational study recruited 30,138 adult patients (treatment-naive or previously treated with ranibizumab or other ocular treatments) who were treated according to the local ranibizumab label., Results: Six thousand two hundred and forty-one treatment-naive neovascular age-related macular degeneration patients were recruited. Baseline (BL) demographics were, mean (SD) age 75.0 (10.2) years, 54.9% females, and 66.5% Caucasian. The mean (SD) visual acuity (VA; letters) gain at 1 year was 3.1 (16.51) (n = 3,379; BLVA, 51.9 letters [Snellen: 20/92]) with a mean (SD) of 5.0 (2.7) injections and 8.8 (3.3) monitoring visits. Presented by injection frequencies <3 (n = 537), 3 to 6 (n = 1,924), and >6 (n = 918), visual acuity gains were 1.6 (14.93), 3.3 (16.57), and 3.7 (17.21) letters, respectively. Stratified by BLVA <23 (n = 382), 23 to <39 (n = 559), 39 to <60 (n = 929), 60 to <74 (n = 994), and ≥74 (n = 515), visual acuity change was 12.6 (20.63), 6.7 (17.88), 3.6 (16.41), 0.3 (13.83), and -3.0 (11.82) letters, respectively. The incidence of ocular/nonocular adverse events was 8.2%/12.8% and serious adverse events were 0.9%/7.4%, respectively., Conclusion: These results demonstrate the effectiveness and safety of ranibizumab in treatment-naive neovascular age-related macular degeneration patients.

Purpose: To compare visual outcomes and treatment burden between intravitreally administered aflibercept (IVT-AFL) and ranibizumab (RBZ) treat-and-extend (T&E) regimens in patients with wet age-related macular degeneration (wAMD) at 2 years., Methods: A systematic literature review was carried out in Medline, EMBASE, and CENTRAL in October 2018. Matching-adjusted indirect comparison (MAIC) and/or individual patient data meta-regression was used to connect ALTAIR (assessing IVT-AFL T&E) with other studies, adjusting for between-trial differences in baseline visual acuity and age or baseline visual acuity, age, and polypoidal choroidal vasculopathy (PCV) status. Sensitivity analyses were conducted to test the robustness of the results, including direct MAIC between IVT-AFL T&E (ALTAIR) and RBZ T&E (CANTREAT and TREX-AMD trials)., Results: Six randomized controlled trials (RCTs) (ALTAIR, VIEW 1 and 2, CATT, CANTREAT, and TREX) were included in the analysis. IVT-AFL T&E was assessed in one study, ALTAIR (n = 255), while RBZ T&E was assessed in two trials (n = 327). At 2 years, the median difference (95% credibility interval) between IVT-AFL T&E and RBZ T&E regarding the numbers of Early Treatment Diabetic Retinopathy Study (ETDRS) letters gained was not significant (M1: - 2.29 [- 8.10, 3.58]; M2: - 0.55 [- 6.34, 5.29]). IVT-AFL T&E was associated with significantly fewer injections than RBZ-T&E (M1: - 6.12 [- 7.60, - 4.65]; M2: - 5.93 [- 7.42, - 4.45]). Results of the sensitivity analyses were consistent with the main scenarios., Conclusion: Patients with wAMD receiving an IVT-AFL T&E regimen achieved and maintained improvement in visual acuity with fewer injections over 2 years compared with RBZ T&E. IVT-AFL T&E may therefore serve as the optimal therapy for wAMD, as it was associated with clinical efficacy and minimized treatment burden.

Purpose: To evaluate efficacy and safety of intravitreal injections of aflibercept (IVT-AFL) treat-and-extend (T&E) dosing regimens in treatment-naïve patients with exudative age-related macular degeneration (AMD)., Methods: Adults aged at least 50 years old with exudative AMD and best-corrected visual acuity (BCVA) of 73-25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters were included. Patients received three monthly doses of IVT-AFL 2 mg. At week 16, patients were randomized 1:1 to IVT-AFL T&E with either 2- or 4-week adjustments. The primary endpoint was mean change in BCVA from baseline to week 52. Outcomes were assessed at weeks 52 and 96., Results: Baseline characteristics were comparable between the groups (n = 123 each). Over 52 weeks, mean number of injections was 7.2 and 6.9 and mean last injection interval was 10.7 and 11.8 weeks, for the 2- and 4-week groups, respectively. From baseline, mean change in BCVA was + 9.0 and + 8.4 letters (week 52) and + 7.6 and + 6.1 letters (week 96); mean change in central retinal thickness was - 134.4 µm and - 126.1 µm (week 52) and - 130.5 µm and - 125.3 µm (week 96). Last injection interval before week 52 was at least 12 weeks in 42.3% and 49.6% of patients and 56.9% and 60.2% before week 96. Over 96 weeks, mean number of injections was 10.4 (both groups). The safety profile of IVT-AFL was consistent with previous reports., Conclusions: IVT-AFL administered using two different T&E regimens for treatment-naïve exudative AMD improved functional and anatomic outcomes at week 52 and outcomes were maintained to week 96. Outcomes were similar between the 2- and 4-week groups., Trial Registration: ClinicalTrials.gov identifier, NCT02305238.

Purpose: This article evaluates the clinical usefulness of an attachment involving a +20-D lens to gain extended field images on wide-angle optical coherence tomography angiography (OCTA)., Methods: An attachment with a +20-D lens was developed to take OCTA images of anterior segments, and it was used to obtain extended field images of the posterior segment in this study. Ten eyes of 5 individuals who did not have a history of ocular or systemic disease underwent wide-angle OCTA with a 12 × 12-mm center field using the PLEX Elite 9000 with and without the attachment. The ratio of the area of the center field to the area of the extended field with the attachment was calculated., Results: The mean area of the center image was 125 disc areas and that of the field extended by the attachment was 210 disc areas. The mean ratio between the center field and the extended field was 1.67., Conclusions: The attachment involving the +20-D lens seems to be clinically useful to gain extended field images on wide-angle OCTA., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Purpose: To investigate surgical outcomes of macular hole retinal detachment (MHRD) in highly myopic eyes., Design: Multicenter, retrospective case study., Participants: One hundred ten eyes with retinal detachment resulting from macular hole (MH) were evaluated., Methods: The medical records of consecutive patients who underwent vitrectomy between January 2010 and December 2015, inclusive, to treat MHRD in 10 hospitals of the Japan Clinical Retinal Study Team were reviewed., Main Outcome Measures: Retinal reattachment rate and MH closure rate after the initial surgery., Results: One hundred ten eyes of 110 patients were studied. The retina was reattached in 85% of eyes and MH was closed in 52% of eyes after the initial surgery. Eyes with gas tamponade achieved higher reattachment rate than those with silicone oil tamponade., Conclusions: The gas tamponade group achieved better retinal reattachment rate than silicone oil tamponade group. Gas tamponade could be the first choice for MHRD., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy and safety of intravitreal aflibercept injection (IAI) in Japanese patients with diabetic macular edema (DME)., Methods: VIVID-DME was a Phase 3 study comprising patients with DME randomized 1:1:1 to IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 4 weeks until Week 16 then 8-week dosing (2q8), and laser. A total of 403 patients (76 Japanese) were included in this study. VIVID-Japan (72; all Japanese patients) was a nonrandomized, open-label study comprising Japanese patients with DME receiving IAI 2q4 until Week 16, then 2q8. Primary efficacy endpoint (Week 52) of VIVID-DME was mean change from baseline in best-corrected visual acuity; VIVID-Japan evaluated safety and tolerability., Results: Mean change in best-corrected visual acuity (letters) for 2q4, 2q8, and laser groups was +10.6, +10.9, and +1.2 and +9.8, +9.5, and +1.1 in the non-Japanese and Japanese populations of VIVID-DME, respectively. In VIVID-Japan, it was +9.3 for IAI 2q8. Intravitreal aflibercept injection also provided consistently greater benefits for anatomical outcomes versus laser. Adverse events were consistent with the known safety profile of IAI., Conclusion: In Japanese patients with DME, IAI treatment was superior to laser for visual and anatomical outcomes and resulted in efficacy and safety outcomes similar to those in a non-Japanese patient population.

We quantitatively determined the relation between the decrease in orbital fat and enophthalmos due to bimatoprost using magnetic resonance imaging (MRI). Nine orbits in nine patients were treated unilaterally with bimatoprost for glaucoma or ocular hypertension. The contralateral orbits were used as controls. The volumes of the orbital tissues and the enophthalmos were measured using MRI. The mean volumes on the treated and untreated sides were, respectively, 14.6 ± 2.1 and 17.0 ± 4.3 cm3 for orbital fat (P = 0.04) and 3.4 ± 0.5 and 3.3 ± 0.5 cm3 for total extraocular muscles (P = 0.85). The mean enophthalmos values were 14.7 ± 2.5 and 16.0 ± 2.3 mm on the treated and untreated sides, respectively (P = 0.002). The data acquired by quantitatively measuring the volumes of orbital fat and enophthalmos on MRI showed that each might be reduced by bimatoprost administration. The enophthalmos could be caused by the bimatoprost-induced decrease in orbital fat., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Higashiyama: grants from JSPS KAKENHI; personal fees from Senju Pharmaceutical, personal fees from Pfizer Japan, grants from Alcon Japan, grants from Novartis Pharmaceutical Company, outside the submitted work. Minamikawa: personal fees from Alcon Japan, personal fees from Pfizer Japan, personal fees from Kowa Pharmaceutical Company, outside the submitted work. Kakinoki: grants and personal fees from Alcon Japan, grants from Novartis Pharmaceutical Company, outside the submitted work. Sawada: personal fees from Santen Pharmaceutical Company, personal fees from Bayer, personal fees from Kowa Pharmaceutical Company, grants from Alcon Japan, grants and personal fees from Novartis Pharmaceutical Company, outside the submitted work. Ohji: grants from JSPS KAKENHI; grants and personal fees from Alcon Japan, grants and personal fees from Novartis Pharmaceutical Company, grants and personal fees from Santen Pharmaceutical Company, grants and personal fees from Otsuka Pharmaceutical Company, grants and personal fees from Pfizer Japan, grants and personal fees from HOYA Corporation, grants and personal fees from Senju Pharmaceutical Company, personal fees from Allergan Japan, personal fees from Bayer, personal fees from Kowa Pharmaceutical Company, personal fees from Chuo Sangio Company, personal fees from Topcon Corporation, personal fees from RE Medical Inc., personal fees from Carl Zeiss Japan, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aims/introduction: To determine the current clinical preferences of anti-vascular endothelial growth factor (VEGF) treatment protocols for diabetic macular edema (DME) in Japan., Materials and Methods: This was a descriptive cross-sectional study. Answers to a questionnaire consisting of 16 questions were obtained from 176 of 278 (63.3%) surveyed ophthalmologists., Results: The results showed that 81.2% preferred intravitreal injections of anti-VEGF antibodies as the first-line therapy. The most important indicators for beginning anti-VEGF therapy were: the best-corrected visual acuity in 44.3% and the retinal thickness in 30.7%. In the loading phase, 53.4% preferred a single injection, and in the maintenance phase, 75.0% preferred the pro re nata regimen. Financial limitation (85.8%) was reported as the most important difficulty in the treatment. For combination therapy with anti-VEGF treatment, panretinal photocoagulation, focal photocoagulations and a sub-Tenon steroid injection were preferred. The contraindications for anti-VEGF therapy were: prior cerebral infarction (72.7%). Regarding the use of both approved anti-VEGF agents in Japan, ranibizumab and aflibercept, 39.8% doctors used them appropriately., Conclusions: Our results present the current clinical preferences of anti-VEGF treatment for DME in Japan. The best-corrected visual acuity and the retinal thickness are important indicators to institute this therapy. The majority of the ophthalmologists use anti-VEGF treatment as first-line therapy and prefer the 1 + pro re nata regimen., (© 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background and Objective: To evaluate comparability of abicipar pegol (abicipar) effects in patients with treatment-naïve neovascular age-related macular degeneration (nAMD) in Japan and the United States., Patients and Methods: Phase 2, multicenter, randomized, double-masked, 20-week studies (BAMBOO, Japan; CYPRESS, United States). Patients (n = 25 each study) received three monthly intravitreal injections of abicipar 1 mg or 2 mg or five monthly intravitreal injections of ranibizumab 0.5 mg., Results: Mean best-corrected visual acuity change from baseline at week 16 (primary endpoint) for abicipar 1 mg, abicipar 2 mg, and ranibizumab was +7.8 letters, +8.9 letters, and +17.4 letters (BAMBOO); +4.4 letters, +10.1 letters, and +15.2 letters (CYPRESS). Mean central retinal thickness change from baseline was -187.3 μm, -196.5 μm, and -230.4 μm (BAMBOO); -106.5 μm, -112.8 μm, and -124.4 μm (CYPRESS). Uveitis or vitritis was reported in three abicipar-treated patients., Conclusion: Abicipar demonstrated extended duration of effect and safety that were comparable between Japanese and non-Japanese patients with nAMD. Abicipar effectively treated Japanese patients with polypoidal choroidal vasculopathy. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e10-e22.]., (© 2019 Kunimoto, Ohji, Maturi, et al.)

Blue cone monochromacy (BCM) is characterized by loss of function of both OPN1LW (the first) and OPN1MW (the downstream) genes on the X chromosome. The purpose of this study was to investigate the first and downstream genes in the OPN1LW/OPN1MW array in four unrelated Japanese males with BCM. In Case 1, only one gene was present. Abnormalities were found in the promoter, which had a mixed unique profile of first and downstream gene promoters and a -71A > C substitution. As the promoter was active in the reporter assay, the cause of BCM remains unclear. In Case 2, the same novel mutation, M273K, was present in exon 5 of both genes in a two-gene array. The mutant pigments showed no absorbance at any of the wavelengths tested, suggesting that the mutation causes pigment dysfunction. Case 3 had a large deletion including the locus control region and entire first gene. Case 4 also had a large deletion involving exons 2-6 of the first gene. As an intact LCR was present upstream and one apparently normal downstream gene was present, BCM in Case 4 was not ascribed solely to the deletion. The deletions in Cases 3 and 4 were considered to have been caused by non-homologous recombination.

Purpose: To compare the ability of wide-angle optical coherence tomography angiography (OCTA) with that of ultra-wide field fluorescein angiography (UWFFA) to detect non-perfusion areas (NPAs) or retinal neovascularization (NV) in eyes with diabetic retinopathy (DR)., Methods: Patients with DR underwent UWFFA using the Optos® panoramic 200Tx imaging system and wide-angle OCTA with 12 × 12 mm fields of five visual fixations using the PLEX Elite 9000®. We compared the abilities of UWFFA and OCTA to detect NPAs and NV., Results: Fifty-eight eyes of 33 patients (mean age, 60.0 years old; female/male, 16/17) with DR were evaluated. NPAs were detected in 47 out of 58 eyes using UWFFA and in 48 eyes using OCTA. NVs were detected in 25 out of the 58 eyes using UWFFA and in 26 eyes using OCTA. The sensitivity for detection of NPA using OCTA was 0.98, and the specificity was 0.82. The sensitivity for detection of NV was 1.0, and the specificity was 0.97., Conclusion: The wide-angle OCTA seems to be clinically useful for the detection of NPAs or NV.

Background: Three eyes of 2 cases had repeating recurrences and spontaneous closures of macular holes (MHs) after vitrectomy., Cases: A 66-year-old man had rhegmatogenous retinal detachment (RRD) in his left eye and underwent vitrectomy with successful retinal reattachment. A full-thickness MH developed 1 year after the vitrectomy and spontaneously closed 1 month later. Opening and spontaneous closure of the MH recurred an additional 4 times over 7 years. An 80-year-old man had suffered intraocular lens (IOL) dislocation and underwent vitrectomy in his left eye. An MH developed in the eye 6 years and 3 months after the vitrectomy. Repeated opening and spontaneous closure of the MH occurred twice in the left eye. The same patient also suffered IOL dislocation and underwent vitrectomy in his right eye. An MH also developed in the right eye 2 years and 9 months after the vitrectomy. Repeated opening and spontaneous closure of the MH occurred 3 times in the right eye., Observations: The visual acuity was maintained at the last visit in both cases., Conclusions: MHs in vitrectomized eyes can show repeated recurrence and spontaneous closure.

The aim of this study was to compare the axial lengths (ALs) using a new biometer with swept-source optical coherence tomography (Argos) versus ALs using a conventional biometer with partial coherence interferometry (IOL Master, version 5). The ALs in 48 eyes of 48 cataract patients were measured with Argos using refractive indexes that correspond to the particular tissue and with IOL Master using a single refractive index. The eyes were divided into three subgroups by AL length: short-AL group (n = 16), <23.27 mm; intermediate-AL group (n = 16), 23.27-24.03 mm; long-AL group (n = 16), ≥24.04 mm. The ALs (mm) measured with the Argos and IOL Master biometers, respectively, were 22.77 ± 0.43 and 22.74 ± 0.44, 23.63 ± 0.21 and 23.62 ± 0.21, and 26.00 ± 1.61 and 26.05 ± 1.64 in the short-, intermediate-, and long-AL groups, respectively. The mean ALs with the Argos biometer were longer than those with the IOL Master biometer in the short-AL group (P = 0.002) There was no significant difference in the intermediate-AL groups (P = 0.14). In contrast, the mean ALs with the Argos biometer were shorter than those with the IOL Master biometer in the long-AL group (P < 0.001). Differences between the ALs measured with the two biometers were statistically significant in short- and long-AL subgroups. However, the differences might not be clinically significant.

Purpose: To evaluate the clinical validity of the Rabin cone contrast test (RCCT; Innova Systems, Inc.) in patients with normal phakic/pseudophakic eyes and severe dichromatic colour vision deficiency (CVD)., Methods: We evaluated age-related changes in the RCCT scores in 166 phakic eyes and 34 pseudophakic eyes and the RCCT sensitivity and specificity in 28 men with severe dichromatic CVD (10 with protanopia, 18 with deutanopia) and nine age-matched controls. All participants had 20/20 or better Snellen best-corrected visual acuity (BCVA). The RCCT was used to measure the L, M and S-CCT scores (range, 0-100)., Results: In normal phakic eyes, the mean L, M and S-CCT scores decreased gradually with ageing, with normal levels in patients in the second to seventh decades of life and some below normal in the eighth and ninth decades of life. In normal pseudophakic eyes, the mean L, M and S-CCT scores were normal in patients in the seventh to ninth decades of life. In eyes with severe CVD, the mean L, M and S-CCT scores were, respectively, 31.5 ± 18.3, 86.0 ± 12.6 and 98.0 ± 6.3 in patients with protanopia; 92.8 ± 10.5, 50.8 ± 19.6 and 97.8 ± 5.2 in patients with deutanopia; and 99.4 ± 1.7, 98.3 ± 5.0 and 99.4 ± 1.7 in controls. The RCCT sensitivity and specificity were 100% for diagnosing the CVD type., Conclusion: The RCCT can be used in non-visually impaired patients up to the seventh decade of life and after cataract surgery in elderly patients. The RCCT is available for CVD screening and typing and the score has a wide distribution range even in patients with severe CVD., (© 2017 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Importance: Clinical evidence supports the efficacy of bimonthly aflibercept injection for age-related macular degeneration., Background: The study aimed to evaluate aqueous vascular endothelial growth factor and aflibercept concentrations and the efficacy of bimonthly aflibercept in patients with age-related macular degeneration., Design: This study is a prospective, interventional case series., Participants: Enrolled were 35 eyes with exudative age-related macular degeneration from 35 patients., Methods: Patients received three bimonthly intravitreal aflibercept without loading doses. We collected the aqueous humor just before each injection, measured vascular endothelial growth factor and aflibercept concentrations by enzyme-linked immunosorbent assay and measured best-corrected visual acuity and central retinal subfield thickness before and after the injections., Main Outcome Measures: Aqueous vascular endothelial growth factor and aflibercept concentrations were measured., Results: The vascular endothelial growth factor concentration was 135.4 ± 60.5 pg/mL (mean ± standard deviation, range 60.6-323.4) at baseline and below the lowest detectable limit in all eyes at month 2 and in 32 eyes at month 4 (P < 0.001 [month 2] and P < 0.001 [month 4]). The mean aflibercept concentration was 20.3 ng/mL at month 2 and 28.0 ng/mL at month 4. The mean logarithm of the minimum angle of resolution visual acuity improved from 0.50 ± 0.36 at baseline to 0.36 ± 0.40 at month 6 (P < 0.001). The mean central retinal subfield thickness decreased from 353 ± 100 μm at baseline to 236 ± 45 μm at month 6 (P < 0.001)., Conclusions and Relevance: Bimonthly aflibercept injections without loading doses may be considered a treatment option for age-related macular degeneration., (© 2017 Royal Australian and New Zealand College of Ophthalmologists.)

We quantitatively analyzed inflammation in orbital fat from cases of thyroid-associated ophthalmopathy (TAO) using short-tau inversion recovery (STIR) sequences from magnetic resonance imaging. The signal intensity ratios (SIRs) of orbital fat as well as the superior rectus (SR), inferior rectus (IR), lateral rectus (LR), medial rectus (MR), and superior oblique (SO) muscles on STIR images were measured in 70 eyes from 70 treatment-naive TAO patients (active TAO group, 19 patients; inactive TAO group, 51 patients) and 20 eyes from 20 controls. The mean SIR in the active TAO group was significantly higher than that in the inactive TAO group and controls (P < 0.001). The SIR of orbital fat in all TAO patients was significantly (P < 0.001) positively correlated with that of the extraocular muscles: SR (r = 0.64), IR (r = 0.55), LR (r = 0.58), MR (r = 0.71), and SO (r = 0.65). The SIR of orbital fat had a significant positive correlation with the CAS (r = 0.53, P < 0.001). The measurements of SIRs in orbital fat may be useful in evaluating the activity in tissues of TAO patients.

The aim of this study was to investigate changes in the anterior segment of the eye after cycloplegia. A biometer combined with swept-source optical coherence tomography (SSOCT) was used for measurements. Patients with strabismus or amblyopia who underwent cycloplegia were included. The axial length, central corneal thickness, anterior chamber depth, and lens thickness were measured with the biometer-SSOCT system before and after cycloplegia. Altogether, 10 eyes of 10 patients (mean age 7.20 ± 3.08 years, range 4-14 years) were evaluated. The mean measurements before cycloplegia were 22.75 ± 0.96 mm axial length, 516 ± 33 μm central corneal thickness, 3.40 ± 0.21 mm anterior chamber depth, and 3.77 ± 0.26 mm lens thickness. The corresponding values after cycloplegia were 22.75 ± 0.95 mm, 519 ± 34 μm, 3.68 ± 0.16 mm, and 3.42 ± 0.20 mm, respectively. The mean lens thickness had significantly decreased (P < 0.001) after cycloplegia, and the mean anterior chamber depth had significantly increased (P < 0.001). The means of the axial length (P = 0.66) and central corneal thickness (P = 0.17) had not changed significantly. The change in lens thickness was significantly correlated with the change in anterior chamber depth (r = -0.73, P = 0.02). The new biometer-SSOCT combination proved useful for accurately detecting changes in the anterior segment of the eye after cycloplegia in pediatric patients. The biometer's measurements indicated increased anterior chamber depth and decreased lens thickness after cycloplegia. The anterior chamber depth increased relative to the decrease in lens thickness.

Japanese killifish Oryzias latipes were exposed to three levels (0, 1, and 10 µg l -1 ) of copper pyrithione (CuPT 2 ), zinc pyrithione (ZnPT 2 ), six of their degradation products, and the organotin compounds tributyltin (TBT) and triphenyltin (TPT) for 48 h at 20 °C. All individual fish exposed to 1 and 10 µg l -1 of CuPT 2 or 10 µg l -1 of ZnPT 2 were dead within 12 h, respectively, and at 24 h the survival rate of the fish exposed to 1 µg l -1 of ZnPT 2 was 50%. All fish exposed to 10 µg l -1 of ZnPT 2 showed morphological abnormalities in the form of vertebral deformity. None of the fish exposed to six of the degradation products of PTs, TBT, and TPT died during a 48-h exposure period, but various biological effects were observed in the fish exposed to these chemicals: abnormalities of respiration and swimming behavior, and decreased hatchability. Our findings suggest that O. latipes has a higher ecological risk of CuPT 2 and ZnPT 2 exposure than of TBT and TPT exposure during their life history. Because these antifouling biocides have been used in both freshwater and marine environments, our results highlight these biocides' deleterious effects on the freshwater fish as well as marine fish, and they indicate freshwater and marine pollution.

Purpose: To determine the microstructure of the fovea in patients with Stickler syndrome using imaging by spectral-domain optical coherence tomography (SD OCT) and swept-source OCT., Design: Retrospective case series study., Participants: A total of 39 eyes of 25 patients with genetically confirmed Stickler syndrome were studied., Methods: All of the patients had mutations in the COL2A1 gene and were diagnosed with Stickler syndrome. Cross-sectional OCT images, OCT angiography (OCTA), and en face OCT images were assessed. The ratio of the foveal inner retinal layer (fIRL) thickness to the parafoveal inner retinal layer (pIRL) thickness, the ratio of the foveal outer retinal layer (fORL) thickness to the parafoveal outer retinal layer (pORL) thickness, and the size of the foveal avascular zone (FAZ) were determined., Main Outcome Measures: The degree of foveal hypoplasia and the best-corrected visual acuity in patients with Stickler syndrome., Results: A persistence of the inner retinal layers in the fovea with an fIRL/pIRL ratio >0.2 was present in 32 of the 39 eyes (82%). Optical coherence tomography angiography showed that the FAZ was smaller, 0 to 0.19 mm 2 , than that of normal eyes, in 25 eyes of 17 patients who underwent OCTA. There was no significant correlation between the visual acuities and the fIRL/pIRL ratios., Conclusions: A mild foveal hypoplasia with a persistence of the IRL is characteristic of eyes with Stickler syndrome. The visual acuities were not correlated with the fIRL/pIRL ratios., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the microvasculature changes of retinal nerve fiber layer (RNFL) defects in glaucoma., Design: The study design is a case report., Patients and Methods: Four glaucomatous eyes were included in this observational cross-sectional study. The microvasculature changes of RNFL defects were examined using optical coherence tomography (OCT) angiography., Results: Three eyes had apparent wedge-shaped capillary dropout on OCT angiography. In the fourth eye, detection of wedge-shaped capillary loss was difficult because of overall capillary drop out due to advanced glaucoma. Capillary dropout detection by OCT angiography was correlated with visual field loss and RNFL defect detection by regular OCT. Compared with regular OCT used to obtain retinal thickness maps, OCT angiography is often better at visualizing the borders of lesions in the RNFL., Conclusions: OCT angiography can detect capillary dropout in RNFL defects in glaucomatous eyes, and therefore could be a useful glaucoma examination tool.

Purpose: The aim of the study was to investigate blood flow in choroidal neovascular membrane in remission phase of neovascular age-related macular degeneration using optical coherence tomography (OCT) angiography., Methods: OCT angiography was obtained in eyes with remission phase of neovascular age-related macular degeneration after treatments, defined as no exudative change (such as macular edema, subretinal fluid, and subretinal hemorrhage) observed in eyes without any treatment for neovascular age-related macular degeneration within the previous 6 months. Irregular blood flows shown in the segmentation of outer retina detected by OCT angiography were considered as blood flows in choroidal neovascular membrane. The vascular area and vessel density were obtained from OCT angiography images., Results: Twenty eyes of 20 patients were included in this analysis. The blood flows in choroidal neovascular membrane were observed in all eyes (100%) using OCT angiography. The mean vascular area was 3.81 ± 3.41 mm and the mean vessel density of lesion was 28.9 ± 8.2%. The vessel density was significantly correlated with best-corrected visual acuity and duration of remission (best-corrected visual acuity: P = 0.008, r = -0.576; duration of remission: P = 0.017, r = -0.525, respectively)., Conclusion: Optical coherence tomography angiography revealed that blood flows in choroidal neovascular membrane remained in eyes with clinically inactive neovascular age-related macular degeneration.

Objective: To evaluate the retinal perfusion using optical coherence tomography (OCT) angiography in eyes with good visual acuity recovery after treatment for optic neuritis (ON)., Methods: Seven eyes of seven patients with good visual acuity recovery after treatment for monocular ON and seven eyes of each fellow eye used as controls were studied. Retinal perfusion around the disc and at the macula was evaluated using OCT angiography. The retinal nerve fiber layer thickness was measured around the disc. The ganglion cell layer complex thickness or the ganglion cell layer plus the inner plexiform layer thickness were measured at the macula., Results: The retinal perfusions in all eyes with ON decreased around the disc and at the macula compared with those of the fellow eyes, as shown by OCT angiography (disc, P = 0.003; macula, P = 0.001). The retinal thicknesses in all eyes with ON also decreased around the disc and at the macula compared with those of the fellow eyes (disc, P < 0.001; macula, P = 0.003)., Conclusions: Optic neuritis may cause not only retinal structural damage but also decreased retinal perfusion, even after the visual acuity recovered well after treatment., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Higashiyama: Senju Pharmaceutical: Lecture Fee, Pfizer Japan: Lecture Fee. Nishida: None. Ohji: Alcon Japan: Consultant, Lecture Fee, Novartis Pharmaceutical Company: Consultant, Lecture Fee, Santen Pharmaceutical Company: Consultant, Lecture Fee, Bayer: Consultant, Lecture Fee, Shionogi & CO.: Consultant, Lecture Fee, Pfizer Japan: Consultant, Sanwa Kagaku Institute: Consultant, Carl Zeiss Japan: Lecture Fee, Otsuka Pharmaceutical Company: Lecture Fee, MSD: Lecture, and Kowa Pharmaceutical Company: Lecture Fee. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: We compared the efficacy of bimonthly intravitreal injections of ranibizumab (IVR) with that of bimonthly intravitreal injections of aflibercept (IVA) in two prospective, consecutive groups of patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO)., Patients and Methods: Eyes with ME after CRVO received either bimonthly IVR (ranibizumab group; n = 13) or IVA (aflibercept group; n = 13) injections and were followed monthly for 6 months. Three patients in the ranibizumab group and two in the aflibercept group were lost to follow-up and excluded from the study. The best-corrected visual acuity (BCVA), central foveal thickness (CFT) on optical coherence tomography, and aqueous vascular endothelial growth factor (VEGF) concentrations were evaluated before and after treatment., Results: From baseline to month 6, significant improvements occurred in mean logMAR BCVA (ranibizumab group: 0.78-0.47; p < 0.05; aflibercept group: 0.74-0.54; p < 0.05) and mean CFT (ranibizumab group: 685-311 µm; p < 0.05; aflibercept group: 695-230 µm; p < 0.05). Fluctuations in CFT were seen at months 2, 4, and 6 in the ranibizumab group. Mean aqueous VEGF concentration decreased from baseline to month 2 in the ranibizumab group (509.9-348.2 pg/ml) and aflibercept group (412.1 pg/ml to undetectable limits in eight of 11 eyes and to 13.6, 15.6, and 24.1 pg/ml in the other three eyes, respectively)., Conclusions: There was no significant improvement of visual acuity in one group compared with another; VEGF may not be completely neutralized by bimonthly injections of ranibizumab.

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: To investigate anatomic changes in retinal thickness (RT) and functional changes after vitrectomy for idiopathic epiretinal membranes (ERMs) with and without internal limiting membrane (ILM) peeling., Methods: The medical records of 100 eyes of 96 patients with ERM who underwent vitrectomy and ERM removal were reviewed retrospectively. The RT was measured by optical coherence tomography, and the area was divided into 9 sections. The best-corrected visual acuity (BCVA), 9 RT areas, and incidence rates of recurrent ERM were compared between the groups with and without ILM peeling before the operation and 12 months postoperatively., Results: Thirty-nine eyes that underwent vitrectomy with ILM peeling and 61 eyes that underwent vitrectomy without ILM peeling met the inclusion criteria. There were no significant differences between the groups in the BCVA and any of the RTs before the operation and 12 months postoperatively. The ERMs recurred in 8 (20.5%) of 39 eyes and 26 (42.6%) of 61 eyes in the groups with and without ILM peeling, respectively, with a difference that reached significance (p = 0.02) 12 months postoperatively., Conclusions: Vitrectomy for ERM affects the BCVA or the RTs 12 months postoperatively. Additional ILM peeling does not affect them, but it might reduce the ERM recurrence rate., (© 2016 S. Karger AG, Basel.)

Purpose: To investigate the predictive factors for postoperative best-corrected visual acuity (BCVA) in patients with vitreomacular traction syndrome treated with vitrectomy., Methods: The records of 21 patients with 21 eyes that underwent vitrectomy for vitreomacular traction syndrome and followed for at least 12 months were retrospectively reviewed. The BCVA and spectral domain optical coherence tomography findings were investigated preoperatively and at 1, 3, 6, and 12 months postoperatively. Axial length was measured preoperatively. The correlations between 12-month postoperative BCVA and preoperative parameters, including BCVA, age, axial length, central foveal thickness, outer foveal thickness, and photoreceptor outer segment length, were evaluated., Results: Twelve-month postoperative BCVA was significantly negatively correlated with preoperative outer foveal thickness and photoreceptor outer segment length (outer foveal thickness: P = 0.029, r = -0.501; photoreceptor outer segment length: P = 0.022, r = -0.523, respectively) but not correlated with age, axial length, preoperative BCVA, and preoperative central foveal thickness (age: P = 0.346, r = 0.216; axial length: P = 0.333, r = 0.242; BCVA: P = 0.202, r = 0.290; central foveal thickness: P = 0.065, r = -0.410, respectively)., Conclusion: Preoperative outer foveal thickness and photoreceptor outer segment length could be good predictive factors of postoperative BCVA in patients with vitreomacular traction syndrome.

Background: To investigate the effectiveness of vitrectomy for diffuse diabetic macular edema (DDME) and its dependence on optical coherence tomography (OCT) findings., Methods: The records of 65 patients and 81 eyes who received vitrectomy for DDME and followed up for at least 6 months were retrospectively reviewed. All eyes were classified according to their morphological characteristics on OCT including sponge-like diffuse retinal thickening (SDRT: n = 13), cystoid macular edema (CME: n = 42), serous retinal detachment (SRD: n = 13), and the combination of all morphological characteristics (FULL: n = 13). The best-corrected visual acuity (BCVA) and spectral domain OCT were investigated preoperatively and at 1, 3, and 6 months postoperatively., Results: At six months after surgery, BCVA in logMAR units was significantly improved in all groups except the SDRT group. The improvement was -0.04 ± 0.20 in the SDRT group (P = 0.504), -0.16 ± 0.24 in the CME group (P < 0.01), -0.32 ± 0.32 in the SRD group (P < 0.01), and -0.26 ± 0.19 in the FULL group (P < 0.01), and significantly better in eyes with subretinal fluid (SRF; the SRD and FULL groups) than in eyes without SRF (the SDRT and CME groups, P = 0.003)., Conclusions: Vitrectomy can be a useful treatment option for DDME, particularly for eyes with SRF.

Background and Objective: To evaluate the retinal perfusion in patients with chiasmal compression using optical coherence tomography angiography (OCTA)., Patients and Methods: Retinal perfusion was evaluated using OCT angiograms in eight eyes of four patients with visual field (VF) defects due to chiasmal compression treated by tumor resection. The retinal perfusion in the area corresponding to the quadrants of the VF defects was investigated in each image. The vessel density was defined as the percentage area occupied by the vessels in the image., Results: The decreased peripapillary retinal perfusion correlated with the quadrants of the VF defects on OCT angiograms in all patients. The binarized vessel density decreased, corresponding to the degree of VF defects in all patients., Conclusions: A decrease in peripapillary retinal perfusion correlates with the quadrants of the VF defects due to chiasmal compression. This decrease can be noninvasively measured by OCTA. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:724-729.]., (Copyright 2016, SLACK Incorporated.)

Stickler syndrome is an inherited connective tissue disorder that affects the eyes, cartilage and articular tissues. The phenotypes of Stickler syndrome include congenital high myopia, retinal detachment, premature joint degeneration, hearing impairment and craniofacial anomalies, such as cleft palate and midline facial hypoplasia. The disease is genetically heterogeneous, and the majority of the cases are caused by mutations in the COL2A1 gene. We examined 40 Japanese patients with Stickler syndrome from 23 families to determine whether they had mutations in the COL2A1 gene. This analysis was conducted by examining each patient's genomic DNA by Sanger sequencing. Five nonsense, 4 splicing and 8 deletion mutations in the COL2A1 gene were identified, accounting for 21 of the 23 families. Different mutations of the COL2A1 gene were associated with similar phenotypes but with different degrees of expressivity.