Efficacy, durability, and safety of faricimab with extended dosing up to every 16 weeks in diabetic macular edema: 2-year results from the Japan subgroup of the phase 3 YOSEMITE trial.

PURPOSE: To evaluate the 2-year efficacy, durability, and safety of faricimab in patients with diabetic macular edema (DME) in the YOSEMITE Japan subgroup. STUDY DESIGN: YOSEMITE/RHINE (NCT03622580/NCT03622593) subgroup analysis: global, multicenter, randomized, double-masked, active-comparator-controlled, phase 3 faricimab trials. METHODS: Patients were randomized 1:1:1 to intravitreal faricimab 6.0 mg every 8 weeks (Q8W) and per treat-and-extend (T&E) dosing, or aflibercept 2.0 mg Q8W. Outcomes were assessed through year 2 for the YOSEMITE Japan subgroup (N = 60) and the pooled YOSEMITE/RHINE global cohort (N = 1891). RESULTS: In the YOSEMITE Japan subgroup, 21, 19, and 20 patients were randomized to faricimab Q8W, faricimab T&E, and aflibercept Q8W, respectively (632, 632, and 627 patients in the pooled YOSEMITE/RHINE cohort). Vision gains and anatomic improvements with faricimab at year 1 were maintained over 2 years and were generally consistent between groups. Mean best-corrected visual acuity changes from baseline at year 2 (weeks 92-100 average) for the YOSEMITE Japan subgroup were +12.5, +9.0, and +5.0 letters in the faricimab Q8W, faricimab T&E and aflibercept Q8W arms, respectively (+10.8, +10.4, and +10.3 letters in the pooled YOSEMITE/RHINE cohort). At week 96, 61.1% of the YOSEMITE Japan subgroup and 78.1% of the pooled YOSEMITE/RHINE cohort were on ≥ Q12W dosing. Faricimab was well-tolerated with a safety profile comparable with aflibercept. CONCLUSION: Faricimab up to Q16W offered durable vision gains and anatomic improvements up to 2 years in patients with DME in the YOSEMITE Japan subgroup. Outcomes were generally consistent with the pooled YOSEMITE/RHINE cohort.

Æ©excessA1C index, the sum of yearly excess HbA1c values during the total period of diabetes, may have the potential to predict retinopathy by a linear regression setting regardless of duration in type 1 diabetes: a subgroup analysis of DCCT/EDIC data.

Aims: To find an index of glycemic exposure that predicts retinopathy by a simple regression setting regardless of duration in type 1 diabetes which might be useful for the care of diabetes. Materials and methods: To exclude the possible disturbing effect of metabolic memory, we examined a subgroup of patients with glycohemoglobin A1c (A1C) data for the total period of type 1 diabetes selected from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications data. Three indices-(1) mean value of yearly A1C (mA1C), (2) sum of yearly A1C values (Æ©A1C), and (3) sum of yearly A1C values above 6.5% (Æ©excessA1C)-were assessed as potential candidates. Development of retinopathy was defined by ≥ 3-steps' progression of retinopathy from baseline. Results: The areas under the receiver operating characteristics curves of the indices for development of retinopathy at years 5, 9, and 13 after the onset of diabetes were the same: 0.8481, 0.8762, and 0.8213, respectively, indicating that each index was substantially capable of predicting development of retinopathy at each timepoint. Linear regression analyses showed that each index had significant and substantial linear relations to retinopathy at each timepoint: all P < 0.0001 for slopes; contribution rate R2 = 0.21 (year 5), 0.46 (year 9), and 0.48 (year 13) for each index. But only Æ©excessA1C index appeared to have similar linear relations to retinopathy at all three timepoints (interactions by timepoint: for slopes: P = 0.1393; for intercepts: P = 0.9366). Conclusion: Æ©excessA1C may have the potential to predict retinopathy by just one linear regression setting regardless of duration in type 1 diabetes.

Correction: Æ©excessA1C index, the sum of yearly excess HbA1c values during the total period of diabetes, may have the potential to predict retinopathy by a linear regression setting regardless of duration in type 1 diabetes: a subgroup analysis of DCCT/EDIC data.

[This corrects the article DOI: 10.1007/s13340-023-00654-w.].

Efficacy, durability, and safety of faricimab with extended dosing up to every 16 weeks in Japanese patients with diabetic macular edema: 1-year results from the Japan subgroup of the phase 3 YOSEMITE trial.

PURPOSE: To evaluate efficacy, durability, and safety of faricimab in Japanese patients with diabetic macular edema (DME). STUDY DESIGN: Subgroup analysis of 2 global, multicenter, randomized, double-masked, active-comparator-controlled, phase 3 trials (YOSEMITE, NCT03622580; RHINE, NCT03622593). METHODS: Patients with DME were randomized 1:1:1 to intravitreal faricimab 6.0 mg every 8 weeks (Q8W), faricimab 6.0 mg per personalized treatment interval (PTI), or aflibercept 2.0 mg Q8W through week 100. Primary endpoint was best-corrected visual acuity (BCVA) change from baseline at 1 year, averaged over weeks 48, 52, and 56. This is the first time 1-year outcomes between Japanese patients (only enrolled into YOSEMITE) and the pooled YOSEMITE/RHINE cohort (N = 1891) have been compared. RESULTS: The YOSEMITE Japan subgroup included 60 patients randomized to faricimab Q8W (n = 21), faricimab PTI (n = 19), or aflibercept Q8W (n = 20). Consistent with global results, the adjusted mean (95.04% confidence interval) BCVA change at 1 year in the Japan subgroup was comparable with faricimab Q8W (+11.1 [7.6-14.6] letters), faricimab PTI (+8.1 [4.4-11.7] letters), and aflibercept Q8W (+6.9 [3.3-10.5] letters). At week 52, 13 (72%) patients in the faricimab PTI arm achieved ≥ Q12W dosing, including 7 (39%) patients receiving Q16W dosing. Anatomic improvements with faricimab were generally consistent between the Japan subgroup and pooled YOSEMITE/RHINE cohort. Faricimab was well tolerated; no new or unexpected safety signals were identified. CONCLUSION: Consistent with global results, faricimab up to Q16W offered durable vision gains and improved anatomic and disease-specific outcomes among Japanese patients with DME.

Comparison of the Effect of Bromfenac versus Betamethasone Ophthalmic Solutions in Patients with Diabetic Macular Edema.

PURPOSE: To examine the effect of 0.1% bromfenac (BF) ophthalmic solution and 0.1% betamethasone (BM) ophthalmic solution on diabetic macular edema (DME). METHODS: This was a prospective trial. Nineteen patients (mean age of 66.6 ± 10.1 years) with DME and mean retinal thickness within a diameter of 1 mm from the fovea (central subfield thickness: CST) of 250-500 µm were randomized and instilled with BF or BM. CST, best-corrected visual acuity (BCVA), and intraocular pressure (IOP) were measured at 4, 8, and 12 weeks after administration. RESULTS: CST at baseline (p = .128) and that at 4, 8, and 12 weeks of administration was not significantly different between the BF (10 patients) and BM groups (9 patients). In patients with glycated hemoglobin (HbA1c) <8.0%, CST, compared with baseline, was significantly decreased in the BF group (seven patients) at 8 (p = .025) and 12 weeks (p = .043) of administration. When compared with the baseline, no significant changes in BCVA were observed at any point in time in either group. Baseline IOP was comparable between the groups. In the BM group, the values of change in IOP from baseline significantly increased at 8 (p = .025) and 12 weeks (p = .044) of administration, with no significant changes in IOP over the 12 weeks of administration in the BF group. CONCLUSIONS: BF did not affect IOP even after 12 weeks of administration, suggesting its effect in reducing CST in DME with good glycemic control. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN-CTR); UMIN000026201, February 18, 2017; Japan Registry of Clinical Trials; jRCTs031180308, March 15, 2019.

Correction: Sugimoto et al. Trends in the Prevalence and Progression of Diabetic Retinopathy Associated with Hyperglycemic Disorders during Pregnancy in Japan. J. Clin. Med. 2022, 11, 165.

In the original publication [...].

Treatment of diabetic macular edema in real-world clinical practice: The effect of aging.

AIMS/INTRODUCTION: In older patients, the management of diabetic macular edema (DME) can be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME. MATERIALS AND METHODS: This is a real-world clinical study including 1,552 patients with treatment-naïve center-involved DME. The patients were categorized into 4 categories by age at baseline (C1, <55; C2, 55-64; C3, 65-74; and C4, ≥75 years). The outcomes were the change in logarithm of the minimum angle of resolution best-corrected visual acuity (logMAR BCVA) and central retinal thickness (CRT), and the number of treatments from baseline to 2 years. RESULTS: From baseline to 2 years, the mean changes in logMAR BCVA from baseline to 2 years were -0.01 in C1, -0.06 in C2, -0.07 in C3, and 0.01 in C4 (P = 0.016), and the mean changes in CRT were -136.2 µm in C1, -108.8 µm in C2, -100.6 µm in C3, and -89.5 µm in C4 (P = 0.008). Treatments applied in the 2 year period exhibited decreasing trends with increasing age category on the number of intravitreal injections of anti-VEGF agents (P = 0.06), selecting local corticosteroid injection (P = 0.031), vitrectomy (P < 0.001), and laser photocoagulation outside the great vascular arcade (P < 0.001). CONCLUSIONS: Compared with younger patients with DME, patients with DME aged ≥75 years showed less frequent treatment, a lower BCVA gain, and a smaller CRT decrease. The management and visual outcome in older patients with DME would be unsatisfactory in real-world clinical practice.

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.

Is Chronic Kidney Disease Affecting the Postoperative Complications of Vitrectomy for Proliferative Diabetic Retinopathy?

Chronic kidney disease (CKD) is a well-known risk factor for postoperative complications in several surgical fields. However, although prevalent among diabetic candidates for vitrectomy, the effect of CKD on vitrectomy outcomes remains unclear. This study aimed at clarifying the relationship between CKD and the occurrence of vitrectomy-related complications in patients with proliferative diabetic retinopathy (PDR). The 6-month incidences of vitreous hemorrhage (VH) and neovascular glaucoma (NVG) following vitrectomy for PDR were compared among the following groups: stages 1-2 CKD (60 patients), stages 3-5 CKD (70 patients not on hemodialysis), and hemodialysis (HD; 30 patients). We also determined whether the deterioration of the estimated glomerular filtration rate (eGFR) was associated with post-vitrectomy events. The incidence of VH was significantly higher in the stages 3-5 CKD group (43%) than in the stages 1-2 CKD (10%) and HD (10%) groups. NVG was more common in the stages 3-5 CKD group (17%) than in the stages 1-2 CKD (2%) and HD (0%) groups. The reduced estimated glomerular filtration rate (eGFR) was the only significant variable associated with post-vitrectomy VH and NVG. Patients with PDR and CKD, particularly those with lower eGFR, might be at risk for post-vitrectomy VH and NVG.

Potential bias of preoperative intravitreal anti-VEGF injection for complications of proliferative diabetic retinopathy.

PURPOSE: Intravitreal anti-VEGF injection (IVI) is administered before vitrectomy to assist management of proliferative diabetic retinopathy (PDR)-related complications. In the clinical setting, retinal surgeons determine the use of preoperative IVI based on individual criteria. In this study, we investigated factors related to the potential bias of retinal surgeons in using IVI prior to vitrectomy for PDR-related complications, and evaluated the real-world outcomes of surgeon-determined preoperative IVI. METHODS: Medical records of 409 eyes of 409 patients who underwent 25-gauge vitrectomy for PDR complications at seven Japanese centers (22 surgeons) were retrospectively reviewed. Ocular factors, demographic and general clinical factors, surgical procedures, and postoperative complications were compared between IVI group (patients who received preoperative IVI; 87 eyes, 21.3%) and non-IVI group (patients who did not receive preoperative IVI; 322 eyes, 78.7%). In addition, baseline HbA1c in IVI group and non-IVI group was compared between eyes with and without postoperative complications. RESULTS: At baseline, IVI group was younger (P<0.001), had shorter duration of diabetes treatment (P = 0.045), and higher frequencies of neovascular glaucoma [NVG] (P<0.001) and tractional retinal detachment [TRD] (P<0.001) compared to non-IVI group. Although IVI group had higher frequencies of intraoperative retinal break and tamponade procedure, there were no significant differences in postoperative complications and additional treatments between two groups. Baseline HbA1c levels were also not correlated with postoperative complications of VH, NVG, and RD both in IVI group and non-IVI group. Logistic regression analysis identified age (P<0.001, odds ratio [OR] 0.95), presence of NVG (P<0.001, OR 20.2), and presence of TRD (P = 0.0014, OR 2.44) as preoperative factors in favor of IVI. CONCLUSIONS: In this multicenter real-world clinical study, younger age and presence of NVG and TRD were identified as potential biases in using IVI before vitrectomy for PDR complications. Eyes that received preoperative IVI had more intraoperative retinal breaks requiring tamponade than eyes not receiving IVI, but postoperative outcome was not different between the two groups.

Trends in the Prevalence and Progression of Diabetic Retinopathy Associated with Hyperglycemic Disorders during Pregnancy in Japan.

The aim of this study was to determine the prevalence and progression of diabetic retinopathy (DR) with hyperglycemic disorders during pregnancy (HDPs) in Japan between 2013 and 2018 using two cohorts. The patients with HDPs were classified as those with pre-existing DM (pexD), gestational DM (GDM), and overt DM (ODM). Cohort 1 was obtained from the health claims database whose diseases were classified by the International Classification of Diseases-10. Cohort 2 was derived from a retrospective, multicenter analysis of the medical records of 225 patients from 10 ophthalmological institutions. In Cohort 1, there were 5268 patients with an HDP prevalence of 8.4%. Among them, 73 of 1139 patients had pexD (6.4%) and 61 of 4129 patients with GDM (1.5%) had DR; the overall prevalence of DR was 2.5%. In Cohort 2, 36 of 225 patients (16.0%) had DR, and 149 patients were followed at the early and late stages of pregnancy. Moreover, 10 of the 102 patients with pexD (9.8%) and two of five patients with ODM (40.0%) had a progression of DR. In conclusion, the prevalence and progression of DR in patients with pexD is lower than previously reported. More attention should be given to pexD and ODM.

Real-world management of treatment-naïve diabetic macular oedema: 2-year visual outcome focusing on the starting year of intervention from STREAT-DMO study.

BACKGROUND/AIMS: To investigate the yearly change of real-world outcomes for best corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve diabetic macular oedema (DMO). METHODS: Retrospective analysis of aggregated, longitudinal medical records obtained from 27 retina specialised institutions in Japan from Survey of Treatment for DMO database. A total of 2049 treatment-naïve centre involving DMO eyes of which the initial intervention started between 2010 and 2015, and had been followed for 2 years, were eligible. As interventions, antivascular endothelial growth factor (VEGF) agents, local corticosteroids, macular photocoagulation and vitrectomy were defined. In each eye, baseline and final BCVA, the number of each intervention for 2 years was extracted. Each eye was classified by starting year of interventional treatment. RESULTS: Although baseline BCVA did not change by year, 2-year improvement of BCVA had been increased, and reached to +6.5 letters in the latest term. There is little difference among starting year about proportions of eyes which BCVA gained >15 letters, in contrast to those which lost >15 letters were decreased by year. The proportion of eyes receiving anti-VEGF therapy was dramatically increased, while those receiving the other therapies were gradually decreased. The proportion of eyes which maintained socially good vision of BCVA>20/40 has been increased and reached to 59.0% in the latest term. CONCLUSION: For recent years, treatment patterns for DMO have been gradually but certainly changed; as a result, better visual gain, suppression of worsened eyes and better final BCVA have been obtained. Anti-VEGF therapy has become the first-line therapy and its injection frequency has been increasing.

Real-world management of treatment-naïve diabetic macular oedema in Japan: two-year visual outcomes with and without anti-VEGF therapy in the STREAT-DME study.

BACKGROUND/AIMS: To investigate real-world outcomes for best-corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve, centr-involving diabetic macular oedema (DME). METHODS: Retrospective analysis of longitudinal medical records obtained from 27 institutions specialising in retinal diseases in Japan. A total of 2049 eyes with treatment-naïve DME commencing intervention between 2010 and 2015 who were followed for 2 years were eligible. Interventions for DME included anti-vascular endothelial growth factor (VEGF) therapy, local corticosteroid therapy, macular photocoagulation and vitrectomy. Baseline and final BCVA (logMAR) were assessed. Eyes were classified by the treatment pattern, depending on whether anti-VEGF therapy was used, into an anti-VEGF monotherapy group (group A), a combination therapy group (group B) and a group without anti-VEGF therapy (group C). RESULTS: The mean 2-year improvement of BCVA was -0.04±0.40 and final BCVA of >20/40 was obtained in 46.3% of eyes. Based on the treatment pattern, there were 427 eyes (20.9%) in group A, 807 eyes (39.4%) in group B and 815 eyes (39.8%) in group C. Mean improvement of BCVA was -0.09±0.39, -0.02±0.40 and -0.05±0.39, and the percentage of eyes with final BCVA of >20/40 was 49.4%, 38.9%, and 52.0%, respectively. CONCLUSION: Following 2-year real-world management of treatment-naïve DME in Japan, BCVA improved by 2 letters. Eyes treated by anti-VEGF monotherapy showed a better visual prognosis than eyes receiving combination therapy. Despite treatment for DME being selected by specialists in consideration of medical and social factors, a satisfactory visual prognosis was not obtained, but final BCVA remained >20/40 in half of all eyes.

Vitreous hemorrhage in diabetes patients with proliferative diabetic retinopathy undergoing hemodialysis.

AIMS/INTRODUCTION: For diabetes patients undergoing hemodialysis, vitreous hemorrhage seems to be a hemodialysis-induced hemorrhagic complication because of the effect of systemic anticoagulation. However, it is unclear whether hemodialysis is associated with vitreous hemorrhage in diabetes patients. We therefore carried out this cohort study to clarify the relationship between hemodialysis and vitreous hemorrhage in diabetes patients with proliferative diabetic retinopathy. MATERIALS AND METHODS: This was a single-center, retrospective, cohort study. We compared the incidence of vitreous hemorrhage in non-vitrectomized proliferative diabetic retinopathy eyes between the hemodialysis group (145 eyes) and peritoneal dialysis group (36 eyes), which does not require the use of systemic anticoagulation (parallel-group study), and in hemodialysis patients in the 12-month period before and after the start of hemodialysis (before-after study). We also determined the risk factors for vitreous hemorrhage after the start of hemodialysis based on the patients' systemic and ophthalmic characteristics. RESULTS: There was no significant difference in the first-year incidence of vitreous hemorrhage between the hemodialysis (23.4%) and peritoneal dialysis groups (22.2%, P = 1.000). The incidence of vitreous hemorrhage in the dialysis period (23.4%) was significantly lower than that in the predialysis period (35.2%, P = 0.008). Only application of panretinal photocoagulation within the 6 months immediately before hemodialysis was significantly associated with the incidence of vitreous hemorrhage after the start of hemodialysis (P < 0.001). CONCLUSIONS: Hemodialysis therapy does not seem to be associated with a higher risk of vitreous hemorrhage in diabetes patients with proliferative diabetic retinopathy.

Prognostic factors of revitrectomy for complications in eyes with proliferative diabetic retinopathy: a retrospective multicentre study.

PURPOSE: To identify prognostic factors for revitrectomy in patients who underwent vitrectomy for complications with proliferative diabetic retinopathy (PDR) in multicentre study. METHODS: Consecutive 452 eyes of 452 patients with PDR undergoing 25-gauge microincision vitrectomy system (MIVS) in seven centres were retrospectivity reviewed. Preoperative ocular factors (baseline visual acuity [VA], vitreous haemorrhage [VH], tractional retinal detachment [TRD] and retinal photocoagulation), general factors (sex, age, diabetes duration, HbA1c level, hypertension, anti-coagulant medication and estimated glomerular filtration rate), surgical procedures (preoperative anti-vascular endothelial growth factor injection, internal limiting membrane peeling, combined cataract surgery, retinal break, and tamponade), postoperative complications for revitrectomy and postoperative VA at 6 months were evaluated. RESULTS: In the follow-up period of 6 months, revitrectomy was performed in 56 eyes (26.3%), and postoperative complications for revitrectomy were VH in 31 eyes (15%), TRD in 13 eyes (6.2%) and membrane proliferation in 12 eyes (5.2%). The mean LogMAR improvement from baseline to 6 months in revitrectomy group (0.39) was significantly worse than in single vitrectomy group (0.74). Diabetic duration, low baseline VA, less simple VH, TRD and air tamponade were statistical risk factors of revitrectomy, and logistic regression analysis identified low baseline VA and air tamponade also as prognostic factors of revitrectomy. CONCLUSION: Our results indicated that prognosis of VA was worse in PDR patients with revitrectomy and low baseline VA and air as the tamponade material were the potential prognostic factors of revitrectomy.

Intraocular pressure elevation after subtenon triamcinolone acetonide injection; Multicentre retrospective cohort study in Japan.

PURPOSE: To evaluate real-world evidence for intraocular pressure (IOP) elevation after subtenon triamcinolone acetonide injection (STTA) in 1252 Japanese patients (1406 eyes) in the Japan Clinical REtina STudy group (J-CREST). METHODS: This was a multicentre retrospective study of the medical records of 1252 patients (676 men (758 eyes); mean age: 63.8 ± 12.9 years) who received STTA in participating centres between April 2013 and July 2017. RESULTS: IOP elevation was observed in 206 eyes (14.7%) and IOP increase ≥ 6 mmHg was found in 328 eyes (23.3%). In total, 106 eyes (7.5%) needed medication and two eyes (0.14%) needed surgical procedures. Younger age, higher baseline IOP, and steroid dose were risk factors associated with IOP elevation. Risk factors associated with IOP increase ≥ 6 mmHg were younger age, lower baseline IOP, steroid dose, and higher incidences of diabetic macular oedema (DME) and uveitis. In contrast, with steroid dose fixed at 20 mg, a lower incidence of DME was a risk factor for increased IOP, suggesting that STTA had dose-dependent effects on IOP increase, especially in patients with DME. CONCLUSION: Our real-world evidence from a large sample of Japanese patients who received STTA showed that the incidence of IOP elevation after STTA was 14.7%, and was associated with younger age, higher baseline IOP, and steroid dose. Thus, IOP should be monitored, especially in patients with younger age, higher baseline IOP, and higher incidences of DME and uveitis.

Outcomes of 25-Gauge Vitrectomy for Tractional and Nontractional Diabetic Macular Edema with Proliferative Diabetic Retinopathy.

The benefit of pars plana vitrectomy with internal limiting membrane peeling for tractional macular edema and diffuse nontractional macular edema in diabetic retinopathy has been reported. Although these studies had included various stages, use of conventional 20-gauge vitrectomy system, small number of cases, single-center study, and lack of retinal structure measurements were limitations. We compared one-year outcomes of 25-gauge vitrectomy for refractory diabetic macular edema with or without the tractional proliferative membrane in proliferative diabetic retinopathy (PDR) eyes and examined the prognostic factors for postoperative visual acuity. A total of consecutive 116 PDR eyes of 116 patients that underwent 25-gauge vitrectomy for tractional macular edema (TME group: 56 eyes) or nontractional macular edema (nTME group: 60 eyes) at six centers were retrospectively reviewed. Visual acuity (VA), central macular thickness (CMT), complications, and postoperative treatments before and 12 months after vitrectomy were compared. Mean VA improved significantly in each group (both P < 0.01), and mean CMT decreased significantly in each group (both P < 0.01). Thirteen eyes underwent additional vitrectomy, six eyes developed neovascular glaucoma, six eyes received intravitreal anti-VEGF injection, and thirteen eyes received subtenon triamcinolone acetonide injection. Multiple linear regression analysis showed that baseline VA and CMT in the TME group and kidney function in the nTME group were the predictable factors of the 12-month postoperative VA. Twenty-five-gauge vitrectomy effectively improved VA and macular structure both in TME and nTME groups. Baseline VA, CMT, and kidney function are important factors affecting postoperative VA.

Risk Factors of Neovascular Glaucoma After 25-gauge Vitrectomy for Proliferative Diabetic Retinopathy with Vitreous Hemorrhage: A Retrospective Multicenter Study.

Neovascular glaucoma (NVG) is a terminal severe complication in eyes with proliferative diabetic retinopathy (PDR), and PDR eyes with vitreous hemorrhage (VH) which undergo vitrectomy may have higher risk of postoperative NVG. The incidence and the prognostic factor of postoperative NVG after 25-gauge vitrectomy with advanced surgical options remain unclear. We retrospectively reviewed medical records of 268 eyes of 268 consecutive PDR patients with VH who underwent 25-gauge vitrectomy and 12 months follow-up at seven centers. Preoperative ocular factors (visual acuity, tractional retinal detachment, panretinal photocoagulation [PRP]), demographics and clinical factors (sex, age, diabetic duration, HbA1c, hypertension, anticoagulant medication, and kidney function), surgical procedures, and postoperative complications were compared between patients who developed postoperative NVG (9.3%) and those who did not. NVG eyes was significantly younger (P = 0.026), had shorter diabetic duration (P = 0.022), higher HbA1c (P = 0.028), absence of PRP (P = 0.039) and higher frequency of postoperative VH (P = 0.0075) than non-NVG eyes. Logistic regression analysis identified postoperative VH (P = 0.014), shorter diabetic duration (P = 0.029), and no PRP (P = 0.028) as prognostic factors for postoperative NVG. This multicenter study indicates that younger age, uncontrolled diabetes, no PRP, and postoperative VH are risk factors of post-vitrectomy NVG.

Elevation of the vitreous body concentrations of oxidative stress-responsive apoptosis-inducing protein (ORAIP) in proliferative diabetic retinopathy.

PURPOSE: Oxidative stress has been implicated in the pathogenesis of various disorders, including diabetic retinopathy (DR). Oxidative stress-responsive apoptosis-inducing protein (ORAIP; a tyrosine-sulfated secreted form of eukaryotic translation initiation factor 5A [eIF5A]) is a recently discovered pro-apoptotic ligand that is secreted from cells in response to oxidative stress and induces apoptosis in an autocrine fashion. This study aimed to determine if ORAIP plays a role in DR. METHODS: To investigate the role of ORAIP in DR, we analyzed the levels of ORAIP in the vitreous body and their relationship with the extent of proliferative diabetic retinopathy (PDR). Enzyme-linked immunosorbent assay was used to quantify the levels of ORAIP, vascular endothelial growth factor (VEGF), C-C motif chemokine ligand 2 (CCL2), interleukin-6 (IL-6), and IL-8 in the vitreous body of 40 eyes from 28 patients with PDR and 11 patients with non-PDR (NPDR). We also analyzed the expression of ORAIP in insoluble proliferative tissues from vitreous body samples by immunofluorescent staining. RESULTS: The vitreous body concentration of ORAIP was significantly (P = 0.0433) higher in the PDR group (52.26 ± 8.68 [mean ± SE] ng/mL, n = 29) than in the NPDR group (28.21 ± 7.30 ng/mL, n = 11). However, there were no significant correlations between the concentration of ORAIP and those of VEGF, IL-6, CCL2, or IL-8. ORAIP expression was observed in the insoluble proliferative tissues in vitreous body samples of most patients in the PDR group, whereas almost no expression of ORAIP was observed in patients in the NPDR group. CONCLUSIONS: Our findings strongly suggest that ORAIP plays a role in oxidative stress-induced retinal injury and may be a sensitive diagnostic marker and a promising therapeutic target for oxidative stress-induced cytotoxicity.

Factors associated with non-proliferative diabetic retinopathy in patients with type 1 and type 2 diabetes: the Japan Diabetes Complication and its Prevention prospective study (JDCP study 4).

AIMS: This study aims to identify associations of non-proliferative diabetic retinopathy (NPDR) in the Japan Diabetes Complication and its Prevention prospective (JDCP) study, a nation-wide study capturing real-world practice for diabetes in Japan. METHODS: We recruited patients with type 1 and type 2 diabetes mellitus aged between 40 and 75 years from 464 hospitals and clinics. Seven thousand and seven hundred patients fulfilled the inclusion criteria, and 5852 patients were included for this specific analysis. Multiple logistic regression models were used to identify associated factors of NPDR. RESULTS: Of the 363 patients with type 1 diabetes, 83 patients (22.8%) had NPDR; there were significant associations of duration of diabetes and high-density lipoprotein cholesterol with the presence of NPDR. Of the 5489 patients with type 2 diabetes, 1515 (27.6%) had NPDR. Female, duration of diabetes, lifetime maximum body weight, treatment types, systolic blood pressure, and the number of oral hypoglycemic agents (OHA) and antihypertensive drug were associated with increased odds of having NPDR. Diastolic BP, body mass index, alcohol intake, and the number of lipid-lowering drugs were associated with lower odds of having NPDR. Statin and fibrate use was associated with lower odds of having NPDR; this association was confirmed in the model adjusting for the propensity score for taking fibrate or statin (odds ratio 0.80, 95% confidence interval 0.70-0.92; p = 0.002). CONCLUSIONS: There was a potential protective association of lipid-lowering medication (statin or fibrate) and statin use and the presence of NPDR in patients with type 2 diabetes in the JDCP study.