Different Factors Associated with 2-Year Outcomes in Patients with Branch versus Central Retinal Vein Occlusion Treated with Ranibizumab.

PURPOSE: To investigate characteristics associated with visual and anatomic outcomes in branch and central retinal vein occlusion (BRVO and CRVO) patients treated with ranibizumab. DESIGN: Post hoc analysis of patients with BRVO and CRVO from 2 multicenter clinical trials who completed month 12 of the HORIZON extension trial. PARTICIPANTS: 205 patients with BRVO and 181 patients with CRVO who completed month 12 of the extension trial. METHODS: With the use of logistic regression, covariates with a P value < 0.20 from univariate analysis were included in multivariate models to identify independent factors associated with a given outcome (at P < 0.05), with preset variables of disease duration and original treatment assignment. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) ≥20/40 (≥70 letters), gain ≥15 letters, and central subfield thickness (CST) ≤250 µm at HORIZON month 12. RESULTS: In patients with BRVO, good baseline BCVA (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.30-1.79), male sex (OR, 2.48; 95% CI, 1.20-5.13), and normal hematocrit (low vs. normal, OR, 0.26; 95% CI, 0.12-0.59) predicted BCVA ≥20/40; high central foveal thickness (OR, 1.03; 95% CI, 1.01-1.04) and normal hematocrit (low vs. normal, OR, 0.31; 95% CI, 0.15-0.66) predicted BCVA improvement ≥15 letters; and extensive baseline subretinal fluid modestly predicted CST ≤250 µm (OR, 1.08; 95% CI, 1.00-1.16). In patients with CRVO, good baseline BCVA (OR, 1.59; 95% CI, 1.35-1.89), never smoking (OR, 2.80; 95% CI, 1.27-6.17), and young age (OR, 0.58; 95% CI, 0.41-0.82) predicted BCVA ≥20/40; never smoking (OR, 2.13; 95% CI, 1.03-4.39), young age (OR, 0.41; 95% CI, 0.28-0.59), poor baseline BCVA (OR, 0.82; 95% CI, 0.73-0.93), hypertension (OR, 4.47; 95% CI, 1.70-11.75), and low diastolic ocular perfusion pressure (OPP) throughout the study (OR, 0.39; 95% CI, 0.21-0.72) predicted BCVA improvement ≥15 letters; and young age (OR, 0.65; 95% CI, 0.47-0.90), lower mean hematocrit (low vs. normal, OR, 2.81; 95% CI, 1.06-7.49), high systolic OPP throughout the study (OR, 1.61; 95% CI, 1.14-2.27), large areas of central hemorrhage (OR, 1.44; 95% CI, 1.04-2.00), and no subretinal fluid (OR, 2.15; 95% CI, 1.06-4.40) predicted CST ≤250 µm. CONCLUSIONS: There are substantial differences in good outcome factors in CRVO versus BRVO, suggesting differences in pathophysiology. Young age, never smoking, hemodilution, and hypertension/high systolic perfusion pressure are more beneficial in CRVO, suggesting that avoidance of sluggish blood flow and maintenance of perfusion may be particularly important in CRVO.

Early Detection of Radiation Retinopathy in Pediatric Patients Undergoing External Beam Radiation Using Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVE: Detection of early vascular changes observed on optical coherence tomography angiography (OCTA) in children who have received external beam radiation and are at risk of developing radiation retinopathy (RR). PATIENTS AND METHODS: Eleven pediatric patients (20 eyes) with history of irradiation and nine healthy subjects (14 eyes) were retrospectively studied after dilated fundus exam and imaging. RESULTS: Four eyes of three patients had clinical RR. Eyes with radiation exposure but no RR had worse vision (no RR: logMAR 0.09 ± 0.14, Snellen 20/25) than controls (logMAR 0.01 ± 0.03, Snellen 20/21; P = .04) and increased superficial foveal avascular zone (FAZ) area (radiation: 0.31 ± 0.15 vs. control: 0.18 ± 0.10; P = .005). Eyes with RR had worse vision (RR: logMAR 0.34 ± 0.31, Snellen 20/44) than eyes with no RR (P = .001) and had increased deep FAZ (RR: 1.23 ± 0.40 vs. no RR: 0.68 ± 0.25; P = .01), but similar superficial FAZ (RR: 0.44 ± 0.28 vs. no RR: 0.31 ± 0.15; P = .42). CONCLUSIONS: Eyes with mildly decreased vision but no RR show superficial but not deep plexus changes. Eyes with RR have both superficial and deep plexus changes. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:145-152.].

Short-term effects of intravitreal bevacizumab in contrast sensitivity of patients with diabetic macular edema and optimizing glycemic control.

AIMS: To analyze contrast sensitivity of intravitreal bevacizumab injections with optimizing glycemic control versus optimizing glycemic control (in combination with sham injections) in eyes with Diabetic Macular Edema (DME). DESIGN: Prospective, interventional, masked, randomized controlled trial. METHODS: Forty-one eyes of 34 patients with type 2 diabetes mellitus and DME with glycated hemoglobin (HbA1c) < 11% received either intravitreal bevacizumab injection (Group 1) or sham injection (Group 2) at 0 and 6 weeks along with optimizing glycemic control. Mean change in best-corrected visual acuity (BCVA), contrast sensitivity (CS), optical coherence tomography (OCT)-measured by central macular thickness (CMT) were compared and correlated at baseline, 2, 6 and 12 weeks. RESULTS: The study showed a mean CS improved in group 1 from 1.14 ±â€¯0.36 logCS to 1.32 ±â€¯0.24 logCS and also in group 2 from 1.11 ±â€¯0.29 logCS to 1.18 ±â€¯0.29 logCS at 12 weeks (P = 0.12). CS and CMT promptly decreased in group 1 compared to group 2 at 2 weeks (ΔCS = 0.15 ±â€¯0.25 vs. 0.03 ±â€¯0.15 logCS; P = 0.04; ΔCMT = 116 ±â€¯115 vs. 17 ±â€¯71 µm; P = 0.01). There was a mean reduction of approximately 0.5% in HbA1c levels in both groups at 12 weeks (P = 0.002). CONCLUSION: The use of bevacizumab in combination with optimizing glycemic control results in earlier improvement of contrast sensitivity in type 2 diabetes patients with DME. However, the optimizing glycemic control itself has shown also to be effective at 12 weeks. ClinicalTrials.gov Identifier: NCT02308644.

Pro-permeability Factors in Diabetic Macular Edema; the Diabetic Macular Edema Treated With Ozurdex Trial.

PURPOSE: The Diabetic Macular Edema Treated with Ozurdex (DMEO) Trial measured aqueous pro-permeability factors (PPFs) in diabetic macular edema (DME) patients before and after injection of dexamethasone implant or vascular endothelial growth factor (VEGF)-neutralizing protein and correlated changes in levels with changes in excess foveal thickness (EFT) to identify potential PPFs contributing to DME. DESIGN: Prospective, randomized crossover clinical trial. METHODS: Twenty DME patients randomized to dexamethasone implant or VEGF-neutralizing protein had aqueous taps and spectral-domain optical coherence tomography (SDOCT) at baseline and every 4 weeks for 28 weeks. Aqueous levels of 55 vasoactive proteins were measured with protein array. Crossover at week 16 provided changes in protein levels after each intervention in all 20 patients. RESULTS: After dexamethasone implant there was significant correlation between changes in levels of 13 vasoactive proteins with changes in EFT, including 3 known PPFs: angiopoietin-2 (r = 0.40, P = .001), hepatocyte growth factor (HGF; r = 0.31, P = .02), and endocrine gland-VEGF (EG-VEGF, r = 0.43, P < .001). Reduction of prolactin, insulin-like growth factor binding protein-3, and matrix metalloproteinase-9 correlated with edema reduction after injection of a VEGF-neutralizing protein as well as dexamethasone implant, suggesting their modulation is likely secondary to changes in edema rather than causative. CONCLUSIONS: Correlation of edema reduction with reduction in the PPFs angiopoietin-2, HGF, and EG-VEGF provides potential insight into the multifactorial molecular mechanism by which dexamethasone implants reduce edema and suggest that additional study is needed to investigate the contributions of these 3 factors to chronic DME.

Assessment of estimated retinal atrophy progression in Stargardt macular dystrophy using spectral-domain optical coherence tomography.

AIMS: To estimate disease progression based on analysis of macular volume measured by spectral-domain optical coherence tomography (SD-OCT) in patients affected by Stargardt macular dystrophy (STGD1) and to evaluate the influence of software errors on these measurements. METHODS: 58 eyes of 29 STGD1 patients were included. Numbers and types of algorithm errors were recorded and manually corrected. In a subgroup of 36 eyes of 18 patients with at least two examinations over time, total macular volume (TMV) and volumes of all nine Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields were obtained. Random effects models were used to estimate the rate of change per year for the population, and empirical Bayes slopes were used to estimate yearly decline in TMV for individual eyes. RESULTS: 6958 single B-scans from 190 macular cube scans were analysed. 2360 (33.9%) showed algorithm errors. Mean observation period for follow-up data was 15 months (range 3-40). The median (IQR) change in TMV using the empirical Bayes estimates for the individual eyes was -0.103 (-0.145, -0.059) mm3 per year. The mean (±SD) TMV was 6.321±1.000 mm3 at baseline, and rate of decline was -0.118 mm3 per year (p=0.003). Yearly mean volume change was -0.004 mm3 in the central subfield (mean baseline=0.128 mm3), -0.032 mm3 in the inner (mean baseline=1.484 mm3) and -0.079 mm3 in the outer ETDRS subfields (mean baseline=5.206 mm3). CONCLUSIONS: SD-OCT measurements allow monitoring the decline in retinal volume in STGD1; however, they require significant manual correction of software errors.

Changes in Retinal Nonperfusion Associated with Suppression of Vascular Endothelial Growth Factor in Retinal Vein Occlusion.

PURPOSE: To assess changes in retinal nonperfusion (RNP) in patients with retinal vein occlusion (RVO) treated with ranibizumab. DESIGN: Secondary outcome measure in randomized double-masked controlled clinical trial. PARTICIPANTS: Thirty-nine patients with central RVO (CRVO) and 42 with branch RVO (BRVO). METHODS: Subjects were randomized to 0.5 or 2.0 mg ranibizumab every month for 6 months and then were re-randomized to pro re nata (PRN) groups receiving either ranibizumab plus scatter laser photocoagulation or ranibizumab alone for an additional 30 months. MAIN OUTCOME MEASURES: Comparison of percentage of patients with increased or decreased area of RNP in patients with RVO treated with 0.5 versus 2.0 mg ranibizumab, during monthly injections versus ranibizumab PRN, and in patients treated with ranibizumab PRN versus ranibizumab PRN plus laser. RESULTS: In RVO patients given monthly injections of 0.5 or 2.0 mg ranibizumab for 6 months, there was no significant difference in the percentage who showed reduction or increase in the area of RNP. However, regardless of dose, during the 6-month period of monthly injections, a higher percentage of patients showed a reduction in area of RNP and a lower percentage showed an increase in area of RNP compared with subsequent periods of ranibizumab PRN treatment. After the 6-month period of monthly injections, BRVO patients, but not CRVO patients, randomized to ranibizumab PRN plus laser showed significantly less progression of RNP compared with patients treated with ranibizumab PRN. CONCLUSIONS: Regardless of dose (0.5 or 2.0 mg), monthly ranibizumab injections promote improvement and reduce progression of RNP compared with PRN injections. The addition of scatter photocoagulation to ranibizumab PRN may reduce progression of RNP in patients with BRVO, but a statistically significant reduction was not seen in patients with CRVO.

Scatter Photocoagulation Does Not Reduce Macular Edema or Treatment Burden in Patients with Retinal Vein Occlusion: The RELATE Trial.

PURPOSE: To determine whether scatter and grid laser photocoagulation (laser) adds benefit to ranibizumab injections in patients with macular edema from retinal vein occlusion (RVO) and to compare 0.5-mg with 2.0-mg ranibizumab. DESIGN: Randomized, double-masked, controlled clinical trial. PARTICIPANTS: Thirty-nine patients with central RVO (CRVO) and 42 with branch RVO (BRVO). METHODS: Subjects were randomized to 0.5 mg or 2.0 mg ranibizumab every 4 weeks for 24 weeks and re-randomized to pro re nata ranibizumab plus laser or ranibizumab alone. MAIN OUTCOME MEASURES: Mean change from baseline best-corrected visual acuity (BCVA) at week 24 for BCVA at weeks 48, 96, and 144 for second randomization. RESULTS: Mean improvement from baseline BCVA at week 24 was 15.5 and 15.8 letters in the 0.5-mg and 2.0-mg CRVO groups, and 12.1 and 14.6 letters in the 0.5-mg and 2.0-mg BRVO groups. For CRVO, but not BRVO, there was significantly greater reduction from baseline mean central subfield thickness (CST) in the 2.0-mg versus 0.5-mg group (396.1 vs. 253.5 µm; P = 0.03). For the second randomization in CRVO patients, there was no significant difference from week 24 BCVA in the ranibizumab plus laser versus the ranibizumab only groups at week 48 (-3.3 vs. 0.0 letters), week 96 (+0.69 vs. -1.6 letters), or week 144 (+0.4 vs. -6.7 letters), and a significant increase from week 24 mean CST at week 48 (+94.7 vs. +15.2 µm; P = 0.05) but not weeks 96 or 144. For BRVO, there was a significant reduction from week 24 mean BCVA in ranibizumab plus laser versus ranibizumab at week 48 (-7.5 vs. +2.8; P < 0.01) and week 96 (-2.0 vs. +4.8; P < 0.03), but not week 144, and there were no differences in mean CST change from week 24 at weeks 48, 96, or 144. Laser failed to increase edema resolution or to reduce the ranibizumab injections between weeks 24 and 144. CONCLUSIONS: In patients with macular edema resulting from RVO, there was no short-term clinically significant benefit from monthly injections of 2.0-mg versus 0.5-mg ranibizumab injections and no long-term benefit in BCVA, resolution of edema, or number of ranibizumab injections obtained by addition of laser treatment to ranibizumab.

Pro-Permeability Factors After Dexamethasone Implant in Retinal Vein Occlusion; the Ozurdex for Retinal Vein Occlusion (ORVO) Study.

PURPOSE: To correlate aqueous vasoactive protein changes with macular edema after dexamethasone implant in retinal vein occlusion (RVO). DESIGN: Prospective, interventional case series. METHODS: Twenty-three central RVO (CRVO) and 17 branch RVO (BRVO) subjects with edema despite prior anti-vascular endothelial growth factor (VEGF) treatment had aqueous taps at baseline and 4 and 16 weeks after dexamethasone implant. Best-corrected visual acuity (BCVA) and center subfield thickness were measured every 4 weeks. Aqueous vasoactive protein levels were measured by protein array or enzyme-linked immunosorbent assay. RESULTS: Thirty-two vasoactive proteins were detected in aqueous in untreated eyes with macular edema due to RVO. Reduction in excess foveal thickness after dexamethasone implant correlated with reduction in persephin and pentraxin 3 (Pearson correlation coefficients = 0.682 and 0.638, P = .014 and P = .003). Other protein changes differed among RVO patients as edema decreased, but ≥50% of patients showed reductions in hepatocyte growth factor, endocrine gland VEGF, insulin-like growth factor binding proteins, or endostatin by ≥30%. Enzyme-linked immunosorbent assay in 18 eyes (12 CRVO, 6 BRVO) showed baseline levels of hepatocyte growth factor and VEGF of 168.2 ± 20.1 pg/mL and 78.7 ± 10.0 pg/mL, and each was reduced in 12 eyes after dexamethasone implant. CONCLUSIONS: Dexamethasone implants reduce several pro-permeability proteins providing a multitargeted approach in RVO. No single protein in addition to VEGF can be implicated as a contributor in all patients. Candidates for contribution to chronic edema in subgroups of patients that deserve further study include persephin, hepatocyte growth factor, and endocrine gland VEGF.

Predictors of Functional and Anatomic Outcomes in Patients with Diabetic Macular Edema Treated with Ranibizumab.

OBJECTIVE: To investigate baseline predictors of month 24 best-corrected visual acuity (BCVA) and central foveal thickness (CFT) in patients with diabetic macular edema (DME) treated monthly with ranibizumab or sham. DESIGN: Post hoc analysis of DME patients in 2 identical phase 3 studies. PARTICIPANTS: Patients randomized to ranibizumab (n = 502) or sham (n = 257). METHODS: Multivariate regression on predictors with P < 0.20 in univariate logistic regression using backward selection to retain predictors with P < 0.05. MAIN OUTCOME MEASURES: Patient characteristics correlating with month 24 BCVA in Early Treatment Diabetic Retinopathy Study letter score ≥70 (20/40) or ≤50 (20/100), gain or loss from baseline BCVA of ≥15, or CFT ≤250 µm. RESULTS: Baseline predictors of BCVA ≥20/40 in ranibizumab-treated patients were good BCVA, submacular fluid, no cardiovascular disease, no scatter photocoagulation, and male gender, whereas in sham-treated patients, they were mild increase in CFT, presence of hard exudates in center subfield, and absence of renal disease. Predictors of improvement in BCVA letter score ≥15 in ranibizumab-treated patients were poor BCVA, submacular fluid, young age, and short diabetes duration, and those in sham-treated patients were poor BCVA, young age, and mild increase in CFT. Predictors of resolution of edema (CFT ≤250 µm) in ranibizumab-treated patients were mild foveal thickening and prominent subfoveal fluid, and those in sham-treated patients were poor BCVA, mild foveal thickening, and statin usage. Month 24 BCVA ≤20/100 was predicted by poor baseline BCVA in ranibizumab-treated patients, and by poor baseline BCVA, large intraretinal cystoid spaces, renal disease, and absence of hypercholesterolemia in sham-treated patients. Loss of BCVA ≥15 letters was predicted in sham-treated patients by submacular fluid, intraretinal cystoid spaces, and renal disease. CONCLUSIONS: Patients with DME and submacular fluid, intraretinal cysts, severe thickening, or renal disease respond poorly when untreated and respond well to ranibizumab treatment. Elimination of submacular fluid, intraretinal cysts, and severe thickening are important goals of DME treatment, and in patients with renal disease, treatment should be very aggressive, with a goal of eliminating all macular fluid.

Is There Excess Oxidative Stress and Damage in Eyes of Patients with Retinitis Pigmentosa?

Retinitis pigmentosa (RP) is a group of diseases in which a mutation in one of the large variety of genes causes death of rod photoreceptors. After rods die, cone photoreceptors gradually die resulting in constriction of visual fields and eventual blindness in many patients. Studies in animal models of RP have demonstrated that oxidative damage is a major contributor to cone cell death. In this study, we extended those findings to patients with RP, because compared to control patients, those with RP showed significant reduction in the reduced to oxidized glutathione (GSH/GSSG) ratio in aqueous humor and a significant increase in aqueous protein carbonyl content. In contrast, there was no significant decrease in the serum GSH/GSSG ratio or increase in carbonyl content of serum proteins. These data indicate that patients with RP have ocular oxidative stress and damage in the absence of manifestations of systemic oxidative stress and/or damage indicating that demonstrations of oxidative damage-induced cone cell death in animal models of RP may translate to human RP. These observations lead to the hypothesis that potent antioxidants will promote cone survival and function in patients with RP and that the aqueous GSH/GSSG ratio and carbonyl content on proteins may provide useful biomarkers. Antioxid. Redox Signal. 23, 643-648.

Fixation Stability Measurement Using Two Types of Microperimetry Devices.

PURPOSE: We compared the fixation stability measurements obtained with two microperimeters, the Micro Perimeter 1 (MP-1) and the Spectral OCT/SLO (OCT/SLO), in subjects with and without maculopathies. METHODS: A total of 41 eyes with no known ocular diseases and 45 eyes with maculopathies were enrolled in the study. Both eyes of each participant had a 20-second fixation test using the MP-1 and OCT/SLO. The bivariate contour ellipse area (BCEA) was used for fixation stability evaluation. RESULTS: In the normal group, BCEA was 2.93 ± 0.32 log minarc2 on OCT/SLO and 2.89 ± 0.30 log minarc2 on MP-1. In the maculopathy group, BCEA was 3.05 ± 0.41 log minarc2 on OCT/SLO and 3.15 ± 0.46 log minarc2 on MP-1. There was no statistically significant difference between the BCEA measured by OCT/SLO and by MP-1 in both groups. A moderate correlation was found between the two devices (r = 0.45, P < 0.001). The sample size during the fixation test was 535.5 ± 14.6 pairs of coordinates in the normal group and 530.7 ± 14.9 pairs in the maculopathy group with MP-1, while it was 72.3 ± 6.9 and 59.9 ± 10.1, respectively, with OCT/SLO. This was due to different tracking frequencies between the two microperimeters. CONCLUSION: Fixation stability assessment yields similar results using the OCT/SLO and MP-1. A major difference in sampling rate between the two microperimeters does not significantly affect BCEA measurements. TRANSLATIONAL RELEVANCE: Fixation stability assessments are comparable and interchangeable between the OCT/SLO and the MP-1.

Regression of choroidal neovascularization results in macular atrophy in anti-vascular endothelial growth factor-treated eyes.

PURPOSE: To determine the incidence and progression of macular atrophy in patients with neovascular age-related macular degeneration (AMD) treated with vascular endothelial growth factor (VEGF) antagonists. DESIGN: Retrospective interventional case series. METHODS: All patients with neovascular AMD treated by the same physician during a 12-month period of ascertainment had all images from their entire follow-up period evaluated, and areas of retina that developed atrophy were compared to the same areas prior to the onset of anti-VEGF treatment. Longitudinal measurements of retinal atrophy were made. RESULTS: In 39 patients, 52 eyes with neovascular AMD were identified. We excluded 5 eyes from analysis (4 had retinal pigment epithelium tears, and 1 had a laser scar). Fundus photographs of the remaining eyes showed that 18/47 eyes (38%) contained hypopigmented areas suggestive of atrophy within the macula at some time during follow-up. Spectral-domain optical coherence tomography confirmed that these areas had loss of retinal pigmented epithelium and ellipsoids zones, with or without subretinal material suggestive of subretinal fibrosis. Comparison of fundus photographs with fluorescein angiograms showed that in 13/18 eyes (72%), atrophy developed in areas previously occupied by choroidal neovascularization, and the other 5 eyes had atrophy prior to the onset of anti-VEGF treatment. The mean (± standard deviation) rate of increase in pure atrophic areas (no subretinal material) was 0.7 ± 0.8 mm(2) per year, with a range of 0.01-2.6 mm(2)/year. CONCLUSION: Treatment of neovascular AMD with a VEGF-neutralizing protein can result in regression of choroidal neovascularization, which is sometimes associated with atrophy of overlying retina.

Treatment of diabetic macular edema with an inhibitor of vascular endothelial-protein tyrosine phosphatase that activates Tie2.

PURPOSE: AKB-9778 is a small-molecule competitive inhibitor of vascular endothelial-protein tyrosine phosphatase (VE-PTP) that promotes Tie2 activation and reduces vascular leakage and neovascularization in mouse models. The purpose of this study was to test the safety, tolerability, pharmacokinetics, and biological activity of AKB-9778 in patients with diabetic macular edema (DME). DESIGN: Open-label, dose-escalation clinical trial. PARTICIPANTS: Four dose cohorts of 6 patients with DME self-administered subcutaneous injections of 5 mg, 15 mg, 22.5 mg, or 30 mg AKB-9778 twice daily for 4 weeks. METHODS: Patients were seen weekly during a 4-week treatment period for safety assessments, best-corrected visual acuity (BCVA) assessment by Early Treatment Diabetic Retinopathy Study protocol, and measurement of central subfield thickness (CST) by spectral-domain optical coherence tomography. Additional safety assessments were performed at 6, 8, and 12 weeks. MAIN OUTCOME MEASURES: Safety assessments, change from baseline BCVA, and change from baseline CST. RESULTS: All doses were well tolerated. A modest, transient reduction in blood pressure and adverse events consistent with vasodilatory activity of AKB-9778 emerged at doses of 22.5 mg or more twice daily. At the week 4 primary end point, BCVA improved 5 letters or more from baseline in 13 of the 18 patients receiving 15 mg or more twice daily; 1 patient improved by 10 to 15 letters, and 2 patients improved by more than 15 letters. Among 18 patients receiving 15 mg or more twice daily, CST decreased by more than 100 µm in 5 patients and by 50 to 100 µm in 2 patients. There was a significant correlation between reduction in CST and improvement in BCVA. CONCLUSIONS: No safety concerns were identified after systemic administration of AKB-9778 for 4 weeks in patients with DME, and doses of 15 mg or more twice daily reduced macular edema and improved vision in some patients. This is a preliminary demonstration of clinical safety and efficacy of a VE-PTP inhibitor and Tie2 activator.

A randomized controlled trial of panretinal photocoagulation with and without intravitreal ranibizumab in treatment-naive eyes with non-high-risk proliferative diabetic retinopathy.

PURPOSE: To compare the efficacy of panretinal photocoagulation (PRP) and intravitreal ranibizumab injection with PRP alone in patients with treatment-naive bilateral non-high-risk proliferative diabetic retinopathy. METHODS: Sixty eyes of 30 patients were randomized either to the study group (SG) receiving PRP plus 2 ranibizumab injections or to the control group (CG) receiving PRP alone. Mean change in best-corrected visual acuity and in optical coherence tomography were compared at baseline and 1, 3, and 6 months. RESULTS: Best-corrected visual acuity was significantly better at 6 months in the SG; however, there was decrease in best-corrected visual acuity in the CG. Central macula thickness decreased significantly at 6 months in SG when compared with baseline (-47.6 µm, P < 0.001) and did not reveal significant difference in the CG. In eyes with diabetic macular edema, best-corrected visual acuity increased by 3.6 letters (P = 0.06) in the SG and decreased by 4.4 letters in the CG (P = 0.003). Central macula thickness decreased by 69.3 µm (P = 0.001) in the SG and decreased by 45.5 µm (P = 0.11) in the CG. CONCLUSION: Intravitreal ranibizumab in combination with PRP can be an effective treatment in eyes with non-high-risk proliferative diabetic retinopathy and diabetic macular edema.

Assessment of Central Retinal Sensitivity Employing Two Types of Microperimetry Devices.

PURPOSE: To compare the retinal sensitivity measurements obtained with two microperimeters, the Micro-Perimeter 1 (MP-1) and the Optos optical coherence tomography (OCT)/scanning laser ophthalmoscope (SLO) in subjects with and without maculopathies. METHODS: Forty-five eyes with no known ocular disease and 47 eyes with maculopathies were examined using both microperimeters. A contrast-adjusted scale was applied to resolve the different stimuli and background luminance existing between the two devices. RESULTS: There was a strong ceiling effect with the MP-1 in the healthy group, with 90.1% (1136 of 1260) test points clustered at 20 dB. The mean sensitivity for the corresponding points in the OCT/SLO was 25.8 ± 1.9 dB. A floor effect was also observed with the OCT/SLO in the maculopathy group with 9.7% (128 of 1316) points clustered at 9-dB values. The corresponding mean sensitivity in the MP-1 was 1.7 ± 3.9 dB. A regression equation between the two microperimeters was established in the common 10 to19 dB intervals as: OCT/SLO = 15.6 + 0.564 × MP-1 - 0.009 × MP-12 + k (k is an individual point constant; MP-1 coefficient P < 0.001; MP-12 coefficient P = 0.006). CONCLUSION: The OCT/SLO and the MP-1 provide two different ranges of contrasts for microperimetry examination. Broadening the dynamic range may minimize the constraint of the ceiling and floor effect. There is a significant mathematical relationship in the common interval of the contrast scale. TRANSLATIONAL RELEVANCE: Applying a unified and broadened dynamic range in different types of microperimeters will help to generate consistent clinical reference for measurements.