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.

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.

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.

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.

Long-term outcomes in patients with retinal vein occlusion treated with ranibizumab: the RETAIN study.

OBJECTIVE: To determine long-term outcomes of patients with ranibizumab-treated retinal vein occlusion (RVO). DESIGN: Prospective follow-up of a subset of patients from 2 phase 3 trials. PARTICIPANTS: Thirty-four patients with branch RVO (BRVO) and 32 with central RVO (CRVO) who completed the Genentech-sponsored ranibizumab study RVO trials. METHODS: Patients seen every month in year 1 and at least every 3 months in year 2 were treated with ranibizumab for intraretinal fluid. Patients requiring injections on consecutive visits were treated with ranibizumab plus scatter photocoagulation. MAIN OUTCOME MEASURES: Mean improvement in best-corrected visual acuity (BCVA) and percentage of patients with edema resolution. RESULTS: With a mean follow-up of 49.0 months, 17 of 34 BRVO patients (50%) had edema resolution defined as no intraretinal fluid for 6 months or more after the last injection. The last injection was given within 2 years of treatment initiation in 76%. The mean number of injections required in unresolved patients in year 4 was 3.2. In patients with resolved edema mean improvement in BCVA was 25.9 letters versus 17.1 letters (P = 0.09) in unresolved patients, and in both groups, approximately 80% had a final BCVA of 20/40 or better. With a mean follow-up of 49.7 months, 14 of 32 CRVO patients (44%) had edema resolution, with 71% receiving their last injection within 2 years of treatment initiation. The mean number of injections in unresolved patients in year 4 was 5.9. Compared with patients with unresolved CRVO, patients with resolved disease had greater improvement in BCVA (25.2 vs. 4.3 letters; P = 0.002), and a greater percentage had a final BCVA of 20/40 or better (64.3% vs. 27.8%; P = 0.04). Nine patients with BRVO and 9 with CRVO received scatter photocoagulation, and with mean follow-up of 9 months (BRVO) and 11 months (CRVO) after last laser, only 1 in each group had resolution of edema. CONCLUSIONS: Long-term outcomes in BRVO patients treated with ranibizumab were excellent, and although half still required occasional injections after 4 years, they maintained good visual potential. A substantial minority (44%) of patients with ranibizumab-treated CRVO had edema resolution and a good outcome within 4 years, but most (56%) still required frequent injections, had reduced visual potential, and have a guarded prognosis.

Long-term outcomes in ranibizumab-treated patients with retinal vein occlusion; the role of progression of retinal nonperfusion.

PURPOSE: To determine the percentage of ranibizumab-treated patients with retinal vein occlusion (RVO) who had resolution of edema for at least 6 months after the last injection, along with factors and outcomes that correlate with resolution. DESIGN: Post hoc analysis of open-label clinical trial. METHODS: Twenty patients with branch RVO (BRVO) and 20 with central RVO (CRVO) received ranibizumab monthly for 3 months and as needed for recurrent/persistent macular edema, no more frequently than every 2 months. Patients still requiring injections after month 40 received scatter and grid laser photocoagulation to try to reduce the need for injections. Main outcome measures included the percentage of patients who had resolution of edema, change in best-corrected visual acuity (BCVA) from baseline, and change in area of retinal nonperfusion in central subfields. RESULTS: Nine patients with BRVO (45%) had edema resolution from injections alone after a mean of 20.2 months, 4 resolved after addition of laser, 4 were unresolved through 72 months, and 3 exited prior to resolution. Five patients with CRVO (25%) resolved from injections alone after a mean of 14.0 months, 8 remained unresolved through 72 months despite addition of laser, and 7 exited prior to resolution. For BRVO or CRVO, there was a negative correlation between posterior retinal nonperfusion area and BCVA at months 18, 24, and 36 (P < .05). CONCLUSIONS: In patients with RVO, infrequent ranibizumab injections to control edema may not be sufficient to prevent progression of retinal nonperfusion, which may contribute to loss of visual gains.

Longitudinal spectral domain optical coherence tomography changes in eyes with intraocular lymphoma.

BACKGROUND: Cases of patients with primary intraocular lymphoma (PIOL) were retrospectively analyzed to describe the longitudinal intra-retinal morphological changes in PIOL as visualized on images obtained by spectral domain optical coherence tomography (SD-OCT). RESULTS: In a retrospective case series, Heidelberg Spectralis SD-OCT images obtained in the longitudinal evaluation of patients with biopsy-proven PIOL were analyzed and assessed. The images were graded for the presence of macular edema (ME), pigment epithelial detachment (PED), subretinal fluid (SRF), and hyperreflective signals. SD-OCT scans of five eyes from five patients were assessed. Patients showed signs of inflammation, such as ME and SRF, which were resolved with treatments in some cases. Hyperreflective signals were found in all eyes in the form of nodules or bands across the retina, with the highest frequency of appearance in the ganglion cell layer, inner plexiform layer, photoreceptor layer, and retinal pigment epithelium; such signals increased with the progression of PIOL. CONCLUSION: SD-OCT may be employed to monitor the progression of PIOL. Hyperreflective signals on OCT may correspond with increase in disease activities, along with other findings such as ME, PED, and SRF.

Ranibizumab for edema of the macula in diabetes study: 3-year outcomes and the need for prolonged frequent treatment.

OBJECTIVE: To assess the benefit of increased follow-up and treatment with ranibizumab between months 24 and 36 in the Ranibizumab for Edema of the Macula in Diabetes (READ-2) Study. DESIGN: Prospective, interventional, multicenter follow-up of a randomized clinical trial. METHODS: Patients who agreed to participate between months 24 and 36 (ranibizumab, 28 patients; laser, 22; and ranibizumab + laser, 24) returned monthly and received ranibizumab, 0.5 mg, if foveal thickness (FTH, center subfield thickness) was 250 µm or greater. Main outcome measures were improvement in best-corrected visual acuity (BCVA) and reduction in FTH between months 24 and 36. RESULTS: Mean improvement from the baseline BCVA in the ranibizumab group was 10.3 letters at month 36 vs 7.2 letters at month 24 (ΔBCVA letters = 3.1, P = .009), and FTH at month 36 was 282 µm vs 352 µm at month 24 (ΔFTH = 70 µm, P = .006). Changes in BCVA and FTH in the laser group (-1.6 letters and -36 µm, respectively) and the ranibizumab + laser group (+2.0 letters and -24 µm) were not statistically significant. The mean number of ranibizumab injections was significantly greater in the ranibizumab group compared with the laser group (5.4 vs 2.3 injections, P = .008) but not compared with the ranibizumab + laser group (3.3, P = .11). CONCLUSIONS: More aggressive treatment with ranibizumab during year 3 resulted in a reduction in mean FTH and improvement in BCVA in the ranibizumab group. More extensive focal/grid laser therapy in the other 2 groups may have reduced the need for more frequent ranibizumab injections to control edema. APPLICATION TO CLINICAL PRACTICE: Long-term visual outcomes for treatment of diabetic macular edema with ranibizumab are excellent, but many patients require frequent injections to optimally control edema and maximize vision. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00407381

Association of retinal sensitivity to integrity of photoreceptor inner/outer segment junction in patients with diabetic macular edema.

PURPOSE: To evaluate the relationship between retinal sensitivity and the photoreceptor inner segment/outer segment (IS/OS) layer status in patients with diabetic macular edema (DME). DESIGN: Cross-sectional study. PARTICIPANTS: Twenty-five adult patients (37 eyes) diagnosed with DME and managed at the Wilmer Eye Institute, Johns Hopkins University (Baltimore, MD). METHODS: We obtained simultaneous fundus microperimetry (MP) and optical coherence tomography (OCT) of patients with DME using a combined MP/OCT system. The device recorded retinal sensitivity and retinal thickness on a 3-dimensional tomography map, and we performed a point-by-point analysis of the IS/OS layer integrity at every MP point. We also reviewed OCT scans to determine the type of DME, cystoid macular edema, or diffuse macular edema (absence of any cysts). In addition, fixation stability and fixation location were analyzed. MAIN OUTCOME MEASURES: Retinal point sensitivity measured by MP. RESULTS: Twenty-five patients (37 eyes: 29 male and 8 female; mean age, 64.16 years) with DME were enrolled. Fixation was centric in 30 eyes (81%), paracentric in 3 eyes (8%), and eccentric in 4 eyes (11%). Twenty-seven eyes had cystoid macular edema, and 10 eyes had diffuse macular edema. Mean central subfield thickness was 325 µm. We analyzed a total of 1036 individual MP points. Mean point sensitivity was 10.51 dB. A total of 793 points (76.5%) had IS/OS layer present, and 243 points (23.5%) had IS/OS layer disrupted. A mixed linear model, constructed to adjust for potential confounders and account for dependence between retinal points, revealed that the absence of the IS/OS junction was significantly associated with a 3.28-dB decrease in retinal point sensitivity (P<0.001). CONCLUSIONS: This novel index study demonstrates that disruption of the IS/OS junction is correlated with a significant decrease in point sensitivity in eyes with DME. Further studies are indicated to confirm and validate this relationship. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Accuracy of computed tomography in diagnosing malignancy in solitary pulmonary lesions.

OBJECTIVE: To evaluate accuracy of Computed Tomography (CT) for diagnosing malignancy in solitary pulmonary lesions (SPLs). METHODS: A prospective cross-sectional study was conducted from 20-01-2007 to 30-06-2008 at the Radiology department, Aga Khan University Hospital (AKUH) Karachi. Fifty-three patients with solitary pulmonary lesions (SPLs) seen in prior chest x-rays or chest CT scans were referred to radiology department for CT guided biopsy. CT scan was performed for each patient prior to biopsy and CT evaluation of the SPLs was performed followed by CT guided Biopsy. Histopathological diagnosis of the lesion was taken as the gold standard. RESULTS: CT was found to be 100% sensitive, 30% specific and 87% accurate for diagnosing malignancy in solitary pulmonary lesions while PPV and NPV were 86% and 100% respectively. CONCLUSION: CT scan is highly sensitive yet non-specific and cannot be used as the definitive diagnostic modality for diagnosing malignancy in solitary pulmonary lesions.