Effects of internal limiting membrane peeling on anatomical and functional outcomes in macula-off rhegmatogenous retinal detachment complicated by proliferative vitreoretinopathy: Japan-Retinal Detachment Registry.

PURPOSE: To investigate the effects of internal limiting membrane (ILM) peeling on retinal attachment after a single surgery, and on postoperative visual acuity (VA) at 6 months, in eyes with macula-off rhegmatogenous retinal detachment (RRD) complicated by proliferative vitreoretinopathy (PVR). STUDY DESIGN: Nationwide, multicenter retrospective cohort study. METHODS: The Japan-RD Registry database was used for analysis of patients who had undergone vitrectomy for macula-off RRD complicated by PVR. Multivariate analysis was performed to detect prognostic factors for retinal attachment after a single surgery and for VA at 6 months postoperatively. Retinal attachment after a single surgery or VA at 6 months postoperatively was the objective variable; ILM peeling, preoperative VA, PVR grade, age, and intraocular pressure were explanatory variables. RESULTS: Eighty-nine eyes met the inclusion criteria; ILM peeling was performed in 25 eyes (28%). Preoperative VA was significantly associated with retinal attachment, but ILM peeling did not (odds ratios = 2.1 and 1.3, respectively; p = 0.009 and 0.67, respectively). Poor preoperative VA and younger patient age were significantly associated with poor postoperative VA, but ILM peeling was not (ß-values = 0.37, -0.008, and 0.15, respectively; p < 0.001, p = 0.02, and p = 0.15, respectively. CONCLUSIONS: Preoperative VA was a risk factor associated with retinal attachment. Preoperative VA and patient age were risk factors associated with postoperative poor VA. In eyes with macula-off RRD complicated by PVR, ILM peeling did not have a clear beneficial effect on anatomical and functional outcomes, suggesting that it may be unnecessary for eyes with this condition.

Subtype prevalence and baseline visual acuity by age in Japanese patients with neovascular age-related macular degeneration.

PURPOSE: To investigate age-specific prevalence of disease subtypes and baseline best-corrected visual acuity (BCVA) in Japanese patients with treatment-naïve neovascular age-related macular degeneration (nAMD). STUDY DESIGN: Retrospective multicenter case series. METHODS: We reviewed the records of patients with treatment-naïve nAMD who underwent initial treatment in 14 institutions in Japan sometime during the period from 2006 to 2015. In patients in whom both eyes were treated, only the eye treated first was included for analysis. The patients were stratified by age for the analysis. RESULTS: In total, 3096 eyes were included. The overall prevalence of subtypes was as follows: typical AMD, 52.6%; polypoidal choroidal vasculopathy (PCV), 42.8%; retinal angiomatous proliferation (RAP), 4.6%. The number of eyes in each age group was as follows: younger than 60 years, 199; 60s, 747; 70s, 1308; 80s, 784; 90 years or older, 58. The prevalence of typical AMD in each age group was 51.8%, 48.1%, 52.1%, 57.7%, and 55.2%, respectively. The prevalence of PCV was 46.7%, 49.1%, 44.7%, 34.4%, and 19.0%, respectively. The prevalence of RAP was 1.5%, 2.8%, 3.2%, 7.9%, and 25.9%, respectively. The prevalence of PCV decreased with age, whilst that of RAP increased. The prevalence of RAP was higher than that of PCV in patients aged 90 years or older. The mean baseline BCVA (logMAR) was 0.53. In each age group, the mean baseline BCVA was 0.35, 0.45, 0.54, 0.62, and 0.88, respectively. The mean logMAR BCVA at baseline significantly worsened with age (P < 0.001). CONCLUSION: The prevalence of nAMD subtypes differed according to age in Japanese patients. The baseline BCVA worsened with age.

Duration of Vascular Endothelial Growth Factor Suppression After Intravitreal Injection of Brolucizumab and Aflibercept in Macaque Eyes.

Purpose: To compare the duration of vascular endothelial growth factor (VEGF) suppression in the aqueous humor of macaque eyes after intravitreal injection of brolucizumab and aflibercept. Methods: Clinical dose of intravitreal brolucizumab (IVBr; 6.0 mg/50 µL) or intravitreal aflibercept (IVA; 2 mg/50 µL) was injected into the right eye of each of 8 macaques. Aqueous humor samples (150 µL) from both eyes were obtained just before injection and on days 1, 3, 7, 14, 21, 28, 42, 56, 84, and 112 after IVBr injection or IVA injection. VEGF concentrations were measured using enzyme-linked immunosorbent assays. Results: In the injected eyes, the mean VEGF suppression durations (range) were 4.9 (3-8) weeks for IVBr injection and 6.8 (6-8) weeks for IVA injection (P = 0.04). The VEGF concentrations returned to the preinjection level in the aqueous humor at 12 weeks both after IVBr and IVA injection. In the noninjected fellow eyes, the aqueous VEGF concentrations had decreased least at 1 day after IVBr injection and at 3 days after IVA injection, but were still detectable. The VEGF concentrations in the fellow eyes returned to the preinjection level in the aqueous humor at 1 week after IVBr injection and at 2 weeks after IVA injection. Conclusions: The duration of VEGF suppression in the aqueous humor after IVBr injection may be shorter than that after IVA injection, which may be related with clinical usage.

Assessment of mouse VEGF neutralization by ranibizumab and aflibercept.

PURPOSE: To assess the interaction between ranibizumab, aflibercept, and mouse vascular endothelial growth factor (VEGF), both in vivo and in vitro. METHODS: In vivo, the effect of intravitreal injection of ranibizumab and aflibercept on oxygen induced retinopathy (OIR) and the effect of multiple intraperitoneal injections of ranibizumab and aflibercept on neonatal mice were assessed. In vitro, the interaction of mouse VEGF-A with aflibercept or ranibizumab as the primary antibody was analyzed by Western blot. RESULTS: In both experiments using intravitreal injections in OIR mice and multiple intraperitoneal injections in neonatal mice, anti-VEGF effects were observed with aflibercept, but not with ranibizumab. Western blot analysis showed immunoreactive bands for mouse VEGF-A in the aflibercept-probed blot, but not in the ranibizumab-probed blot. CONCLUSIONS: Aflibercept but not ranibizumab interacts with mouse VEGF, both in vivo and in vitro. When conducting experiments using anti-VEGF drugs in mice, aflibercept is suitable, but ranibizumab is not.

Essential Roles of Exocyst Complex Component 3-like 2 on Cardiovascular Development in Mice.

Angiogenesis is a process to generate new blood vessels from pre-existing vessels and to maintain vessels, and plays critical roles in normal development and disease. However, the molecular mechanisms underlying angiogenesis are not fully understood. This study examined the roles of exocyst complex component (Exoc) 3-like 2 (Exoc3l2) during development in mice. We found that Exoc3l1, Exoc3l2, Exoc3l3 and Exoc3l4 are expressed abundantly in endothelial cells at embryonic day 8.5. The generation of Exoc3l2 knock-out (KO) mice showed that disruption of Exoc3l2 resulted in lethal in utero. Substantial numbers of Exoc3l2 KO embryos exhibited hemorrhaging. Deletion of Exoc3l2 using Tie2-Cre transgenic mice demonstrated that Exoc3l2 in hematopoietic and endothelial lineages was responsible for the phenotype. Taken together, these findings reveal that Exoc3l2 is essential for cardiovascular and brain development in mice.

Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend Regimens in the ALTAIR Study: 96-Week Outcomes in the Polypoidal Choroidal Vasculopathy Subgroup.

INTRODUCTION: To explore the efficacy and safety of intravitreal aflibercept (IVT-AFL) proactive, individualized treat-and-extend (T&E) regimens in exudative age-related macular degeneration (AMD) in the subgroup of patients with polypoidal choroidal vasculopathy (PCV) enrolled in the ALTAIR study. METHODS: This was a PCV subgroup analysis of ALTAIR, a 96-week, randomized, open-label, phase 4 study in treatment-naïve patients with exudative AMD in Japan. Following three initial monthly doses, patients received IVT-AFL at week 16 and were randomized 1:1 to T&E regimens with either 2-week (IVT-AFL-2W) or 4-week (IVT-AFL-4W) adjustments. The primary endpoint of ALTAIR was the mean change in best-corrected visual acuity (BCVA) from baseline to week 52. Endpoints were assessed at weeks 52 and 96. Safety analyses were conducted. RESULTS: A total of 90 patients with PCV were included within the full analysis set. From baseline to week 52, mean [standard deviation (SD)] change in BCVA was + 7.5 (14.7) letters and + 8.2 (11.6) letters in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. From baseline to week 96, 91.3% and 90.9% of patients maintained vision in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. From baseline to week 52, mean (SD) change in central retinal thickness was - 153 (177) µm and -112 (122) µm in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. Overall, 51.1% of patients (IVT-AFL-2W, 43.5%; IVT-AFL-4W, 59.1%) achieved a treatment interval of 16 weeks between weeks 16 and 96. The safety profile of IVT-AFL was consistent with previous studies. CONCLUSION: In treatment-naïve patients with PCV, IVT-AFL administered using two different T&E regimens improved and maintained functional and anatomic outcomes over 96 weeks while minimizing treatment burden. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02305238.

Impact on visual acuity and psychological outcomes of ranibizumab and subsequent treatment for diabetic macular oedema in Japan (MERCURY).

PURPOSE: The MERCURY study aimed to evaluate the effects on visual acuity and psychological symptoms, and safety, of ranibizumab and subsequent treatment in patients with diabetic macular oedema (DME) and impaired visual acuity (VA). We report data from the prespecified 12-month interim analysis. METHODS: This was a 24-month, phase 4, open-label, single-arm, prospective, observational study conducted at 20 specialised retinal centres in Japan. Participants were 209 patients with DME and impaired VA, not previously treated with either intravitreal or systemic anti-vascular endothelial growth factor (anti-VEGF) agents, who initiated ranibizumab 0.5 mg per investigator discretion. Following ranibizumab administration, patients were treated per routine clinical practice. Other treatments were allowed. The main outcome measure was the mean change in best-corrected VA (BCVA) in logarithmic minimum angle of resolution (logMAR) from baseline to month 12. An exploratory objective was to assess patients' psychological status using the Hospital Anxiety and Depression Scale (HADS). RESULTS: The mean ± standard deviation BCVA at baseline was 0.43 ± 0.39 logMAR. The mean number of injections of ranibizumab and anti-VEGF agents from baseline to month 11 was 3.2 ± 2.0 and 3.6 ± 2.4, respectively. The BCVA change from baseline to 12 months was - 0.08 ± 0.34 logMAR (p = 0.011), showing a significant improvement; the HADS-anxiety score also decreased significantly (p = 0.001) and the depression score decreased numerically (p = 0.080). CONCLUSION: MERCURY study data confirm the effectiveness of real-world treatment initiated with ranibizumab in Japanese patients with DME. In addition, treatment was able to positively influence anxiety via VA improvement.

Optical Coherence Tomography Classification Systems for Diabetic Macular Edema and Their Associations With Visual Outcome and Treatment Responses - An Updated Review.

ABSTRACT: Optical coherence tomography (OCT) is an invaluable imaging tool in detecting and assessing diabetic macular edema (DME). Over the past decade, there have been different proposed OCT-based classification systems for DME. In this review, we present an update of spectral-domain OCT (SDOCT)-based DME classifications over the past 5 years. In addition, we attempt to summarize the proposed OCT qualitative and quantitative parameters from different classification systems in relation to disease severity, risk of progression, and treatment outcome. Although some OCT-based measurements were found to have prognostic value on visual outcome, there has been a lack of consensus or guidelines on which parameters can be reliably used to predict treatment outcomes. We also summarize recent literatures on the prognostic value of these parameters including quantitative measures such as macular thickness or volume, central subfield thickness or foveal thickness, and qualitative features such as the morphology of the vitreoretinal interface, disorganization of retinal inner layers, ellipsoid zone disruption integrity, and hyperreflec-tive foci. In addition, we discuss that a framework to assess the validity of biomarkers for treatment outcome is essentially important in assessing the prognosis before deciding on treatment in DME. Finally, we echo with other experts on the demand for updating the current diabetic retinal disease classification.

Effect of intravitreal bevacizumab for retinopathy of prematurity on weight gain.

PURPOSE: To evaluate the short-term effect on body weight (BW) gain after intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP). METHODS: This was a retrospective 1:1 matched case-control study. Infants with ROP treated by IVB or photocoagulation (PC) at Shiga University of Medical Science Hospital between April 2010 and December 2019 were included in the study. To match BWs at treatment between the IVB and PC groups, 1:1 matching for BWs at treatment within 100 g was performed. The BW gains for the 7 days before treatment (pre-treatment week), the 7 days after treatment (first post-treatment week), and the period from 7 to 14 days after treatment (second post-treatment week) were compared between the IVB and PC groups. RESULTS: Following 1:1 matching, 13 infants in both groups were enrolled in the analysis. The weekly BW gain for the first post-treatment week was significantly lower in the IVB group compared with the PC group (86 g vs. 145 g; P = 0.046), whereas the weekly BW gains for the pre-treatment week (173 g vs. 159 g; P = 0.71) and the second post-treatment week (154 g vs. 152 g; P = 0.73) were comparable between the two groups. The short-term inhibitive effect of IVB on BW gain was particularly observed in infants weighing less than 1500 g at treatment (<1500 g: 47 g vs. ≥1500 g: 132 g; P = 0.03). CONCLUSION: IVB could have a short-term inhibitive effect on BW gain in infants with ROP, and this effect is more likely to occur in infants with a lower BW at the time of treatment.

Treat-and-Extend Regimens for the Management of Neovascular Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy: Consensus and Recommendations From the Asia-Pacific Vitreo-retina Society.

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.

Impact of silicone oil tamponade on intravitreally injected vancomycin pharmacokinetics in cynomolgus monkey eyes.

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.

Systemic adverse events after screening of retinopathy of prematurity with mydriatic.

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.

Effect of internal limiting membrane peeling on postoperative visual acuity in macula-off rhegmatogenous retinal detachment.

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.

Relationship between retinal fluid and visual acuity in patients with exudative age-related macular degeneration treated with intravitreal aflibercept using a treat-and-extend regimen: subgroup and post-hoc analyses from the ALTAIR study.

PURPOSE: To explore the relationship between retinal fluid status and best-corrected visual acuity (BCVA) in patients treated with intravitreal aflibercept (IVT-AFL) treat-and-extend (T&E) in the ALTAIR study. METHODS: Outcomes were investigated according to overall fluid status at week 16 (predefined) and the relationship between any fluid, intraretinal fluid (IRF), subretinal fluid (SRF), or pigment epithelial detachment with BCVA at baseline, and weeks 16, 52, and 96 (post-hoc). The analyses involved treatment-naïve patients (N = 246) with exudative age-related macular degeneration (AMD), aged ≥ 50 years with BCVA of 73-25 Early Treatment Diabetic Retinopathy Study letters, who participated in the ALTAIR study. RESULTS: The mean (standard deviation) change in BCVA from baseline to week 52 was + 10.6 (10.9) and + 6.5 (16.0) letters in patients without and with fluid at week 16, respectively; and to week 96 was + 9.1 (14.3) and + 4.3 (16.1) letters in patients without and with fluid at week 16, respectively. The last injection interval was 16 weeks in 33.6% and 2.0% (week 52), and 62.9% and 17.6% (week 96) of patients without or with fluid at week 16, respectively. At baseline, 35.7% of patients had IRF and 85.2% of patients had SRF, which decreased to 11.8% (IRF) and 31.7% (SRF) of patients, 8.5% (IRF) and 18.7% (SRF), and 6.5% (IRF) and 20.7% (SRF) at weeks 16, 52, and 96, respectively. Presence of IRF at all timepoints was associated with poorer BCVA than if IRF was absent, while the presence of SRF was not associated with poorer BCVA compared with the absence of SRF. CONCLUSION: IVT-AFL T&E dosing was effective at clearing fluid regardless of fluid type in ~ 80% of patients with exudative AMD. Patients without fluid at week 16 had numerically better BCVA than those with fluid at week 16. Over 60% of patients without fluid at week 16 achieved the maximum treatment interval of 16 weeks by study end, compared with < 20% of patients with fluid at week 16. IRF (weeks 16, 52, 96), although evident in a small number of patients, was associated with poorer BCVA, whereas SRF was not. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02305238.

Pharmacokinetics of Intravitreal Vancomycin and Ceftazidime in Silicone Oil-Filled Macaque Eyes.

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.

Evaluation of acquired color vision deficiency in retinal vein occlusion using the Rabin cone contrast test.

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.

The systemic antiangiogenic effect of intravitreal aflibercept injection in a mouse model of retinopathy of prematurity.

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.

THE CORRELATION BETWEEN AQUEOUS VASCULAR ENDOTHELIAL GROWTH FACTOR LEVEL AND CLINICAL ACTIVITY IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

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.

Ten-year changes in visual acuity at baseline and at 2 years after treatment in a Japanese population with age-related macular degeneration.

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.

Safety and efficacy of brilliant blue g250 (BBG) for lens capsular staining: a phase III physician-initiated multicenter clinical trial.

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.