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Purpose: To determine the outcomes of intravenous (IV) tocilizumab (TCZ) in patients with non-infectious uveitis who failed with conventional immunomodulatory and anti-TNFα therapies., Methods: Records of seven patients with non-infectious uveitis treated with monthly IV TCZ (4-10 mg/kg) or biweekly IV TCZ (8 mg/kg) were reviewed. Outcome measures were changes in visual acuity, anterior chamber cell and flare grade, vitreous haze, central subfield thickness (CST), and fluorescein angiography (FA) score., Results: Ten eyes of seven patients received TCZ therapy. Median age of patients was 14 (range, 7-24) years. Median duration of TCZ therapy was 15 (range, 5-32) months. Mean CST reduced from 373 ± 101.0 μm to 298.2 ± 40.3 μm. Mean FA score reduced from 12.5 ± 4.3 to 3.6 ± 2.6. One patient developed elevated liver transaminases., Conclusion: IV TCZ is a potentially effective and safe therapeutic option for the management of refractory non-infectious uveitis.

Objective: To evaluate the safety and efficacy of BI 1467335 in patients with non-proliferative diabetic retinopathy (NPDR)., Methods: ROBIN is a Phase IIa, double-masked, randomised, placebo-controlled study (NCT03238963). Patients with NPDR and without centre-involved diabetic macular oedema were included; all had a best corrected visual acuity letter score of ≥70 Early Treatment Diabetic Retinopathy Study letters in the study eye at screening. Patients received oral BI 1467335 10 mg or placebo once daily for 12 weeks. Post-treatment follow-up was 12 weeks. The primary endpoint was the proportion of patients over the 24 weeks with ocular adverse events (AEs). Secondary endpoints were the proportion of patients with ≥2-step improvement from baseline in DRSS severity level at Week 12 and the proportion of patients with non-ocular AEs at 24 weeks., Results: Seventy-nine patients entered the study (BI 1467335, n = 40; placebo, n = 39). The proportion of patients with ocular AEs over 24 weeks was greater in the BI 1467335 versus the placebo group (35.0% vs 23.1%, respectively). Treatment-related AEs were reported for similar numbers of patients in the placebo and BI 1467335 group (7.7% vs 7.5%, respectively). At Week 12, 5.7% (n = 2) of patients in the BI 1467335 group had a 2-step improvement in DRSS severity level from baseline, compared with 0% in the placebo group., Conclusions: BI 1467335 was well tolerated by patients with NPDR. There was a high variability in DRSS levels for individual patients over time, with no clear efficacy signal., (© 2024. The Author(s).)

Background: This analysis evaluated aqueous humour (AH) interleukin (IL)-6 concentrations and the association between AH IL-6 and visual outcomes in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular oedema (DMO) receiving anti-vascular endothelial growth factor (VEGF) monotherapy., Methods: Post hoc analysis of the multicentre, double-masked, randomised HARBOR (NCT00891735) and READ-3 (NCT01077401) trials. HARBOR enrolled treatment-naïve nAMD patients. READ-3 enrolled treatment-naïve/previously treated DMO patients. HARBOR patients received ranibizumab 0.5 or 2.0 mg monthly or as needed; AH samples were collected at month 2, after two previous intravitreal injections. READ-3 patients received ranibizumab 0.5 or 2.0 mg as needed; AH samples were collected at baseline and months 3, 6, 9, and 12., Main Outcome Measure: association between AH IL-6 concentrations and month 24 best-corrected visual acuity (BCVA)., Results: In both trials (HARBOR, N = 36; READ-3, N = 137), patients with higher AH IL-6 concentrations had worse visual outcomes. HARBOR patients with low AH IL-6 concentrations at month 2 had a mean (95% CI) BCVA change at month 24 of +2.9 (-2.6, 8.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of -9.0 (-22.7, 4.7) letters. READ-3 patients with low AH concentrations at baseline had a mean (95% CI) BCVA change at month 12 of +9.3 (7.4, 11.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of +5.6 (2.2, 9.1) letters., Conclusions: Higher IL-6 AH concentrations may predict suboptimal visual responses to anti-VEGF monotherapy in patients with nAMD/DMO., (© 2024. The Author(s).)

Purpose: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis., Design: Open-label, multicenter, phase 3 extension study (VISUAL III)., Participants: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or who discontinued the study after meeting treatment failure criteria (active uveitis)., Methods: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤ 362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose., Main Outcome Measures: Long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related systemic corticosteroids., Results: At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry. Mean daily dose of systemic corticosteroids was reduced from 9.4 ± 17.1 mg/day at week 0 (n = 359) to 1.5 ± 3.9 mg/day at week 150 (n = 181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest were infections (n = 275; 79 events/100 patient-years [PY]); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively., Conclusions: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Improving or maintaining visual acuity is the main goal for the treatment of neovascular age-related macular degeneration (nAMD). Current nAMD standard of care dictates frequent intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) injections, which places a substantial burden on patients, caregivers, and physicians. Brolucizumab, a newly developed anti-VEGF molecule for nAMD treatment, has demonstrated longer durability and improvement in visual and anatomic outcomes in clinical studies in a q12-week regimen, indicating its potential to reduce treatment burden as an important therapeutic tool in nAMD management. This review focuses on the development of brolucizumab and the preclinical and clinical studies evaluating its efficacy, tolerability, and safety. Brolucizumab (also known as "RTH258" and "ESBA1008") is a humanized, single-chain variable fragment (scFv) antibody with a molecular mass of approximately 26 kDa that inhibits VEGF-A. Preclinical studies show that brolucizumab readily penetrates the retina to reach the retinal pigment epithelium (RPE)/choroid with minimal subsequent systemic exposure. The safety, tolerability, and efficacy of a single IVT brolucizumab administration in patients with treatment-naïve nAMD were first demonstrated in the SEE Phase 1/2 study. The OSPREY Phase 2 study showed brolucizumab to be as efficacious as aflibercept in a q8-week regimen with regard to best-corrected visual acuity (BCVA) and brolucizumab achieving greater fluid resolution. Brolucizumab-treated patients in the OSPREY study were subsequently challenged with a q12-week dosing interval, and the outcomes provided key information for the study design and end points of the Phase 3 studies. In the HAWK and HARRIER Phase 3 studies, after 3 monthly loading injections, brolucizumab treatment regimen (q12-week or q8-week) was guided by individual disease activity assessment using functional and anatomic parameters (central subfield thickness [CST], intraretinal fluid [IRF], or subretinal fluid [SRF]) versus aflibercept (q8-week). Fewer brolucizumab 6-mg treated eyes had disease activity versus aflibercept, and anatomic outcome results at weeks 16 and 48 demonstrate brolucizumab as a potent drying agent. Moreover, of patients treated with 6 mg brolucizumab, 55.6% and 51.0% maintained a q12-week dosing interval immediately after the loading phase until week 48 in HAWK and HARRIER, respectively. These Phase 3 studies demonstrated that the brolucizumab q12-week regimen maintains efficacy and safety while reducing treatment burden associated with regular IVT injections for patients with nAMD., (Copyright © 2020 American Academy of Ophthalmology. All rights reserved.)

Purpose: To investigate the half-life of aflibercept in aqueous humor after a single intravitreal injection in patients with neovascular age-related macular degeneration., Methods: Prospective, noncomparative, interventional case series of five eyes with neovascular age-related macular degeneration naive to anti-vascular endothelial growth factor therapy were enrolled and treated with intravitreal aflibercept. At baseline, best-corrected visual acuity, optical coherence tomography imaging, and aqueous humor (treatment eye) and blood/plasma samples were taken. Patients underwent best-corrected visual acuity, optical coherence tomography imaging, and sampling of aqueous humor from the eye and blood/plasma at six additional post-treatment time points of 4 hours and Days 1, 3, 7, 14, and 28. Concentrations of aflibercept were quantified using an enzyme-linked immunosorbent assay., Results: Median peak concentration (Cmax) of free aflibercept in the aqueous was 122 mg/L. The median half-life of free aflibercept was 11 days in the eye. In plasma, the concentrations of free aflibercept were low and transient, reaching undetectable levels during the first week after injection, and undetectable in all patients at time points beyond 7 days., Conclusion: The pharmacokinetic profile in the aqueous humor described here together with the previously reported affinity of aflibercept for vascular endothelial growth factor is consistent with and adds to our understanding for the duration of its clinical efficacy.

Purpose: To evaluate the thickness of individual retinal layers in eyes with resolved diabetic macular edema (DME) after treatment with ranibizumab (RBZ)., Methods: Spectral-domain optical coherence tomography (OCT) scans of 25 eyes (25 patients) with DME that had been treated with RBZ (and shown resolution of edema as evident by the absence of fluid in a high-resolution grid placed on the fovea) were acquired using Spectralis HRA + OCTTM. Thickness measurements of individual layers were calculated using papillomacular bundle (PMB), central subfield, and inner- and outer-ring Early Treatment Diabetic Retinopathy Study (ETDRS) grids. Measurements were compared to 45 normal eyes with no known retinal disease. A post-hoc analysis was done correlating visual acuity (VA) with individual retinal layer thickness., Results: Full retinal thickness (FRT) was thinner than normal individuals across all 4 grids. There were similarities and differences among the 4 grids; however, PMB and inner-ring ETDRS grids displayed the most resemblance. The VA significantly correlated with the FRT measured in PMB (p = 0.004), central subfield (p = 0.02), and inner-ring (p = 0.006) ETDRS., Conclusions: Segmentation of OCT scans revealed significant differences in the overall thickness of the retina and of individual retinal layers in patients with resolved DME. PMB grid showed a stronger correlation between affected retinal layers and VA compared to ETDRS. PMB also showed significance with VA in layers that were shown to be not significant in ETDRS grid., (© 2019 S. Karger AG, Basel.)

Macular edema is a leading cause of functional visual loss in retinal vascular or ocular inflammatory diseases. Because persistent macular edema can lead to irreversible retinal damage, multi-approached treatment should be considered to achieve complete resolution of macular edema. With an enhanced understanding of its pathophysiology, numerous therapeutic options have been developed for the management of macular edema over the decades. Although medical therapies account for the mainstay of treatment, surgical approaches with vitrectomy can play an important role in the management of macular edema, depending on its mechanism of fluid accumulation. The index review focuses on the efficacy of surgical therapy for macular edema secondary to various ocular diseases including diabetic retinopathy, uveitis, and retinal vein occlusion, and consequently provides the evidences that may expand the knowledge and support the employment of surgical options.

Importance: In a subset of patients with retinal vasculitis, there is occlusion of blood flow through the retinal vessels. These eyes are at high risk of sight-threatening complications., Background: To characterize epidemiology, clinical course, treatment and outcomes of occlusive retinal vasculitis (ORV)., Design: Retrospective study PARTICIPANTS: Seventy-seven uveitis patients with ORV at two large tertiary-care institutions (the USA and India)., Methods: Out of 2438 patients screened, 346 patients were diagnosed with retinal vasculitis of which 77 patients (96 eyes) were diagnosed with ORV. Patients with ORV (capillary, arteriolar and/or venular) were further analysed. Diagnostic criteria for occlusive vasculitis included (i) absence of blood flow in vessels (arterioles, venules and/or capillaries), (ii) capillary non-perfusion areas and/or arteriolar-venous anastomosis and (iii) intraretinal haemorrhages, cotton-wool spots or vitreous haemorrhage., Main Outcome Measures: Best-corrected visual acuity, treatment and complications., Results: The mean age was 32.09 ± 13.51 years. Most common aetiologies were tuberculosis and Adamantiades-Behçet's disease in India and systemic lupus erythematosus in the USA. Best-corrected visual acuity improved from 0.38 ± 0.30 logMAR (20/48 Snellen equivalent) (baseline) to 0.25 ± 0.30 (20/35 Snellen equivalent) at final visit (P < 0.0001). Vitreous haemorrhage was seen in 31.08% eyes. Pars plana vitrectomy was performed in 12.16% eyes. Therapy with systemic steroids was required in 78.48% patients. In addition, 46.75% patients required immunomodulators and/or biologics., Conclusions: Occlusive retinal vasculitis is caused by heterogeneous group of uveitides depending upon the geographic location. It is imperative to identify eyes with ORV as they are predisposed to complications requiring aggressive therapy., (© 2017 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: To report the primary endpoint analyses of the safety and efficacy of 2 different doses of intravenous (IV) infusions of tocilizumab (TCZ), an IL-6 inhibitor, in eyes with noninfectious intermediate uveitis, posterior uveitis, or panuveitis., Design: Randomized, controlled, multicenter clinical trial., Methods: STOP-Uveitis is a randomized, open-label safety, efficacy, and bioactivity clinical trial conducted at 5 clinical centers across the United States. The study evaluated the role of TCZ in patients with noninfectious uveitis (NIU). Thirty-seven patients with NIU were randomized into one of 2 treatment groups in a ratio of 1:1. Group 1 received IV infusions of 4 mg/kg TCZ and group 2 received IV infusions of 8 mg/kg TCZ. Infusions were given every 4 weeks in both groups until month 6 (primary endpoint). Primary outcome measure was incidence and severity of systemic and ocular adverse events through month 6. Secondary outcome measures included mean change in visual acuity (VA), vitreous haze (VH), and central macular thickness (CMT) at month 6., Results: A total of 37 patients were randomized in the study. At month 6, 43.5% of patients who had the potential for a 2-step decrease in VH demonstrated a 2-step decrease (40% in Group 1 and 46.1% in Group 2). Mean change in CMT was -83.88 ± 136.1 μm at month 6 (-131.5 ± 41.56 μm in Group 1 and -38.92 ± 13.7 μm in Group 2). Mean change in VA was +8.22 ± 11.83 ETDRS letters at month 6 (10.9 ± 14.6 in Group 1 and 5.5 ± 7.8 in Group 2). Repeated infusions of TCZ were well tolerated., Conclusions: Repeated IV administrations of TCZ are well tolerated. TCZ (both 4 and 8 mg/kg) is effective in improving VA and reducing VH and CMT in eyes with noninfectious intermediate uveitis, posterior uveitis, and panuveitis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The purpose of this study is to describe an association of unilateral multifocal choroiditis (MFC), retinal vasculitis, optic neuropathy, and bilateral keratoconus in a young Saudi male. A 27-year-old male patient with stable bilateral keratoconus presented with a painless vision loss in his left eye. Ophthalmic examinations revealed multiple foci of idiopathic chorioretinitis, retinal vasculitis, and mild optic disc leakage on fluorescein angiography, all of which resolved on systemic therapy with mycophenolate mofetil and prednisone after 3 months. Systemic medication was stopped after 8 months. One year after presentation, patient's visual acuity has improved and remained stable. Systemic immunomodulatory therapy can be effective in managing and leading to resolution of MFC, retinal vasculitis, and optic disc leak in young patients., Competing Interests: There are no conflicts of interest.

Purpose: To investigate the structure of vitreomacular traction (VMT), specifically, if a correlation exists between 1) the VMT type/grade and the central foveal thickness (CFT) and subfoveal and adjacent choroidal thickness, 2) the vitreomacular/foveal angle (VMFA) and the CFT and subfoveal and adjacent choroidal thickness, and 3) the diameter of vitreomacular adhesion (VMA) and CFT and subfoveal and adjacent choroidal thickness., Materials and Methods: Retrospective, multicenter image analysis study. We analyzed raster scans of the macula taken with spectral-domain optical coherence tomography (SD-OCT) of 61 eyes of 55 patients with VMT. Conventional scans of the vitreoretinal interface were analyzed to measure CFT and the degree of VMFA. Enhanced depth imaging (EDI) scans were analyzed to measure the choroidal thickness in the macula. The multivariate test of means and the t-test were used for statistical comparisons., Results: There was no statistically significant difference in CFT between focal vs broad and concurrent vs isolated type VMT. Central (p = 0.009), nasal (p = 0.004), and temporal (p = 0.007) subfoveal choroidal thickness was significantly higher in broad VMT compared to focal VMT. There was difference in both CFT (p = 0.035) and central (p = 0.005), nasal (p = 0.01), and temporal (p = 0.001) choroidal thickness between moderate and severe VMT. There was a correlation between VMFA and CFT, where a wider angle was associated with increased CFT (p = 0.026). The broader VMA was associated with increased central subfoveal (p = 0.032), nasal (p = 0.05), and temporal (p = 0.01) choroidal thickness., Conclusions: Eyes with broad VMT have thicker choroid than eyes with focal VMT, which have a more open vitreomacular angle. The angle of VMT is related to distinct CFTs.

Purpose: To evaluate the efficacy and safety of intravitreal sirolimus in the treatment of noninfectious uveitis (NIU) of the posterior segment (i.e., posterior, intermediate, or panuveitis)., Design: Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus., Participants: Adults with active NIU of the posterior segment (intermediate, posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects discontinued NIU medications before baseline, except for systemic corticosteroids, which were allowed only for those already receiving them at baseline and were rapidly tapered after baseline per protocol., Methods: Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 μg, administered on Days 1, 60, and 120., Main Outcome Measures: The primary efficacy outcome was the percentage of subjects with VH 0 response at Month 5 (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH 0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to a prednisone-equivalent dosage of ≤5 mg/day), and changes in best-corrected visual acuity (BCVA). Adverse events during the double-masked treatment period are presented., Results: A total of 347 subjects were randomized. Higher proportions of subjects in the intravitreal sirolimus 440 μg (22.8%; P = 0.025) and 880 μg (16.4%; P = 0.182) groups met the primary end point than in the 44 μg group (10.3%). Likewise, higher proportions of subjects in the 440 μg (52.6%; P = 0.008) and 880 μg (43.1%; P = 0.228) groups achieved a VH score of 0 or 0.5+ than in the 44 μg group (35.0%). Mean BCVA was maintained throughout the study in each dose group, and the majority of subjects receiving corticosteroids at baseline successfully tapered off corticosteroids (44 μg [63.6%], 440 μg [76.9%], and 880 μg [66.7%]). Adverse events in the treatment and active control groups were similar in incidence, and all doses were well tolerated., Conclusions: Intravitreal sirolimus 440 μg demonstrated a significant improvement in ocular inflammation with preservation of BCVA in subjects with active NIU of the posterior segment., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare efficacy and safety of intravitreal aflibercept injection (IAI) with macular laser photocoagulation for diabetic macular edema (DME) over 3 years., Design: Two similarly designed phase 3 trials: VISTA DME and VIVID DME ., Participants: Patients (eyes; n = 872) with central-involved DME., Methods: Eyes received IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or laser control. From week 24, if rescue treatment criteria were met, IAI patients received active laser, and laser control patients received IAI 2q8. From week 100, laser control patients who had not received IAI rescue treatment received IAI as needed per retreatment criteria., Main Outcome Measures: The primary end point was the change from baseline in best-corrected visual acuity (BCVA) at week 52. We report the 148-week results., Results: Mean BCVA gain from baseline to week 148 with IAI 2q4, IAI 2q8, and laser control was 10.4, 10.5, and 1.4 letters (P < 0.0001) in VISTA and 10.3, 11.7, and 1.6 letters (P < 0.0001) in VIVID, respectively. The proportion of eyes that gained ≥15 letters from baseline at week 148 was 42.9%, 35.8%, and 13.6% (P < 0.0001) in VISTA and 41.2%, 42.2%, and 18.9% (P < 0.0001) in VIVID, respectively. Greater proportions of eyes treated with IAI 2q4 and IAI 2q8 versus those treated with laser control had an improvement of ≥2 steps in the Diabetic Retinopathy Severity Scale (DRSS) score in both VISTA (29.9% and 34.4% vs. 20.1% [P = 0.0350, IAI 2q4; P = 0.0052, IAI 2q8]) and VIVID (44.3% and 47.8% vs. 17.4% [P < 0.0001 for both]). In an integrated safety analysis, the most frequent ocular serious adverse event was cataract (3.1%, 2.1%, 0.3% for 2q4, 2q8, and control)., Conclusions: Visual improvements observed with both IAI regimens (over laser control) at weeks 52 and 100 were maintained at week 148, with similar overall efficacy in the IAI 2q4 and IAI 2q8 groups. Treatment with IAI also had positive effects on the DRSS score. Over 148 weeks, the incidence of adverse events was consistent with the known safety profile of IAI., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate changes in macular sensitivity, as measured with microperimetry, among patients with maculopathy and stable visual acuity (VA)., Methods: Macular sensitivity was assessed using the Spectral OCT/SLO™ microperimetry (OCT/SLO, Optos Plc., Dunfermline, UK) in 25 eyes (16 patients) with maculopathy and stable VA (<5 letters change in ETDRS score) at two consecutive clinic visits. To take the limits of the test-retest repeatability of the OCT/SLO into account, coefficient of repeatability (CoR) was employed to estimate the probability of the sensitivity changes being secondary to measurement noise., Results: The point sensitivity changes were statistically significant (Wilcoxon signed-rank test, P < 0.001). Seventy-seven points (11 %) out of a total of 700 sensitivity points had a genuine sensitivity change, with a mean increase of 8.6 ± 2.6 dB in 35 points and a mean decrease of 7.9 ± 2.2 dB in 42 points., Conclusions: Point-to-point change in macular sensitivity can be used as a biomarker of changes in disease activity in patients with maculopathy, and can be more accurate than either mean sensitivity or BCVA in detection of changes in macular function. The measurement variability should be considered when observing the local sensitivity changes.

Purpose: To determine bioactivity and duration of effect of intravitreal aflibercept injection (also known as vascular endothelial growth factor Trap-Eye) for neovascular age-related macular degeneration (AMD)., Methods: In this double-masked, phase 1 study, 28 patients with lesions ≤12 disc areas, ≥50% active choroidal neovascularization (CNV), and best corrected visual acuity (BCVA) ≤20/40 were randomized 1:1 to a single intravitreal injection of aflibercept 0.15 or 4 mg. The primary end point was the change from baseline in central retinal/lesion thickness (CR/LT) at week-8. Secondary outcomes were the change from baseline BCVA, the change in CNV lesion size and area of leakage, and proportion of patients requiring repeat injection at 8 weeks., Results: Mean percent decrease in CR/LT for the 4-mg and 0.15-mg groups was, respectively, 34.2 versus 13.3 at week 4 (P=0.0065), 23.8 versus 5.9 at week 6 (P=0.0380), and 25.2% versus 11.3% at week 8 (P=0.150). The 4-mg group gained a mean of 4.5 letters in BCVA (6/14 patients gaining ≥10 letters) versus 1.1 letters in 0.15-mg group (1/14 gaining ≥10 letters) at week 8. Fewer patients needed retreatment in the 4-mg group at week 8. No serious adverse event or ocular inflammation was reported in either group., Conclusions: Intravitreal aflibercept 4 mg had a safety profile similar to that of the very low dose 0.15 mg, and was well-tolerated. The 4-mg dose significantly reduced foveal thickening at weeks 4 and 6, significantly improved BCVA at weeks 6, and reduced the need for repeat injection after 8 weeks compared with intravitreal aflibercept 0.15 mg in neovascular AMD patients.

Purpose: To investigate relationship between macular sensitivity and retinal thickness in diabetic macular edema (DME)., Design: Prospective observational study., Methods: settings: University-based retina practice. patients: Twenty-two eyes of 11 patients with DME. procedure: Fundus microperimetry and retinal thickness tomography were performed simultaneously using an automatic fundus perimetry/tomography system. main outcome measures: Quantification of macular sensitivity, fixation pattern, and relationship between macular sensitivity and retinal thickness., Results: Fixation stability revealed that 21 eyes (95.4%) had stable fixation (>75% within central 2 degrees of point of fixation) and 1 eye (4.5%) had relatively unstable fixation (<75% of fixation points located within 2 degrees, >75% located within 4 degrees). Evaluation of fixation location revealed that 15 eyes (68.2%) had central (>50% of fixation points within 0.5 mm of fovea), 3 eyes (13.6%) pericentral (25% to 50% within 0.5 mm of fovea), and 4 eyes (18.2%) eccentric (<25% of fixation points within 0.5 mm of fovea) fixation location. Macular sensitivity increased by an average of 0.03 decibel (dB) (95% confidence interval [CI]: 0.00, 0.06) per 1-micron (μm) increase in retinal thickness for thickness values ≤280 μm measured with the OPKO/OTI spectral-domain OCT. The macular sensitivity decreased by an average 0.05 dB (95% CI: -0.08, -0.02) per 1-μm increase in thickness for thickness values >280 μm., Conclusions: In this pilot study, the majority of eyes with DME had stable, central fixation. Macular sensitivity varied depending on the thickness of the retina. Additional studies are needed to determine the role of microperimetry in eyes with DME., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To compare optical coherence tomography (OCT)-measured retinal thickness and visual acuity in eyes with diabetic macular edema (DME) both before and after macular laser photocoagulation., Design: Cross-sectional and longitudinal study., Participants: Two hundred ten patients (251 eyes) with DME enrolled in a randomized clinical trial of laser techniques., Methods: Retinal thickness was measured with OCT and visual acuity was measured with the electronic Early Treatment of Diabetic Retinopathy procedure., Main Outcome Measures: Optical coherence tomography-measured center point thickness and visual acuity., Results: The correlation coefficients for visual acuity versus OCT center point thickness were 0.52 at baseline and 0.49, 0.36, and 0.38 at 3.5, 8, and 12 months after laser photocoagulation. The slope of the best fit line to the baseline data was approximately 4.4 letters (95% confidence interval, 3.5-5.3) of better of visual acuity for every 100-mum decrease in center point thickness at baseline with no important difference at follow-up visits. Approximately one third of the variation in visual acuity could be predicted by a linear regression model that incorporated OCT center point thickness, age, hemoglobin A1C, and severity of fluorescein leakage. The correlation between change in visual acuity and change in OCT center point thickening 3.5 months after laser treatment was 0.44, with no important difference at the other follow-up times. A subset of eyes showed paradoxical improvements in visual acuity with increased center point thickening (7%-17% at the 3 time points) or paradoxical worsening of visual acuity with a decrease in center point thickening (18%-26% at the 3 time points)., Conclusions: There is modest correlation between OCT-measured center point thickness and visual acuity, and modest correlation of changes in retinal thickening and visual acuity after focal laser treatment for DME. However, a wide range of visual acuity may be observed for a given degree of retinal edema. Thus, although OCT measurements of retinal thickness represent an important tool in clinical evaluation, they cannot substitute reliably as a surrogate for visual acuity at a given point in time. This study does not address whether short-term changes on OCT are predictive of long-term effects on visual acuity.

To evaluate the correlation between longitudinal changes in aqueous flare measured by laser flare photometer (LFP), best-corrected visual acuity (BCVA), and clinical grade using both Standardization of Uveitis Nomenclature (SUN) and modified SUN (MSUN) scales uveitis patients. Patients were classified according to both SUN and MSUN grading scales. LFP measurements were acquired (Kowa FM-700) at each visit. Mean change in LFP was assessed longitudinally, comparing with those in visual acuity, SUN, and MSUN grading scales. Mean change in LFP was correlated to those in BCVA (p =.018), SUN scale (p <.001), and MSUN scale (p =.008). Cases within same initial SUN (0 and 1+) and MSUN (0.5+ and 1+) grades and different longitudinal flare prognosis (decreased/unchanged/increased) had significantly different initial LFP values (all p <.05). LFP measurement is beneficial in monitoring inflammatory activity. Cases of identical clinical flare scores with different clinical prognosis may be predicted by LFP. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between initial diabetic retinopathy (DR) severity/risk of blindness in patients with newly diagnosed DR/good vision in the U.S.Research Design and Methods: This retrospective cohort study evaluated adult patients with good vision (20/40 or better) and newly diagnosed DR between 1 January 2013 and 31 December 2017 (index date) in the American Academy of Ophthalmology's Intelligent Research in Sight (IRIS) Registry. The primary exposure of interest was DR severity at index: mild nonproliferative DR (NPDR), moderate NPDR, severe NPDR, and proliferative DR (PDR). The main outcome measure was development of sustained blindness (SB), defined as study eyes with Snellen visual acuity readings of 20/200 or worse at two separate visits ≥3 months apart that did not improve beyond 20/100.Results: Among 53,535 eligible eyes (mean follow-up 662.5 days), 678 (1.3%) eyes developed SB. Eyes with PDR at index represented 10.5% (5,629 of 53,535) of the analysis population but made up 26.5% (180 of 678) of eyes that developed SB. Kaplan-Meier analysis revealed that eyes with moderate NPDR, severe NPDR, and PDR at index were 2.6, 3.6, and 4.0 times more likely, respectively, to develop SB after 2 years of DR diagnosis versus eyes with mild DR at index. In a Cox proportional hazards model adjusted for index characteristics/development of ocular conditions during follow-up, eyes with PDR had an increased risk of developing SB versus eyes with mild NPDR at index (hazard ratio 2.26 [95% CI 2.09-2.45]).Conclusions: In this longitudinal ophthalmologic registry population involving eyes with good vision, more advanced DR at first diagnosis was a significant risk factor for developing SB. [ABSTRACT FROM AUTHOR]

The purpose of the study was to assess both anatomic and functional outcomes between short-pulse continuous wavelength and infrared micropulse lasers in the treatment of DME. This was a prospective interventional study from tertiary care eye hospital—King Khaled Eye Specialist Hospital (Riyadh, Saudi Arabia). Patients with center-involving diabetic macular edema were treated with subthreshold laser therapy. Patients in the micropulse group were treated with the 810-nm diode micropulse scanning laser TxCell (IRIDEX Corporation, Mountain View, CA, USA) (subthreshold micropulse—STMP group). Laser was applied according to recommendations for MicroPulse (125 microns spot size, 300 ms pulse duration and power adjustment following barely visible testing burn) in a confluent mode (low intensity/high density) to the entire area of the macular edema. Patients in the short-pulse group were treated with grid pattern laser with 20 ms pulse PASCAL laser 532 nm (TopCon Medical Laser Systems, Tokyo, Japan) with EndPoint algorithm, which was either 30% or 50% of testing burn (EndPoint 30% and EndPoint 50% groups, respectively). Main outcome measures included best-corrected visual acuity (BCVA in logMAR) and foveal thickness at baseline and the last follow-up visit at 6 months. There were 44 eyes in the micropulse group, 54 eyes in the EndPoint 50% group and 18 eyes in the EndPoint 30% group. BCVA for the whole cohort (logMAR) was 0.451 (Snellen equivalent 20/56) at baseline, 0.495 (Snellen equivalent 20/62) (p = 0.053) at 3 months, and 0.494 (Snellen equivalent 20/62) at the last follow-up (p = 0.052). Foveal thickness for the whole cohort was 378.2 ± 51.7 microns at baseline, 347.2 ± 61.3 microns (p = 0.002) at 3 months, and 346.0 ± 24.6 microns at the final follow-up (p = 0.027). As such the short-pulse system yields more temporary reduction in edema. Comparison of BCVA between baseline and 6 months for EndPoint 30%, EndPoint 50% and STMP groups was p = 0.88, p = 0.76 and p = 0.003, respectively. Comparison of foveal thickness between baseline and 6 months for EndPoint 30%, EndPoint 50% and STMP groups was p = 0.38, p = 0.22 and p = 0.14, respectively. We conclude that the infrared micropulse system seems to improve functional outcomes. When applied according to previously published reports, short-pulse system may yield more temporary reduction in edema while infrared micropulse system may yield slightly better functional outcomes. [ABSTRACT FROM AUTHOR]

Background: The current article is a short review of an Alimera Sciences-sponsored symposium held during The 15th International Ocular Inflammation Society Congress in Taiwan on the 14th November 2019 entitled, 'Preventing relapse of non-infectious uveitis effecting the posterior segment of the eye – evaluating the 0.2 μg/day fluocinolone acetonide intravitreal implant.' Main text: The fluocinolone acetonide intravitreal implant was approved in Europe for the prevention of relapse in recurrent non-infectious uveitis affecting the posterior segment of the eye and offers a systemic therapy-sparing treatment option by providing low daily dose of corticosteroid into the vitreous for up to 3 years. In the symposium, the presenters reported clinical outcomes from patients with non-infectious uveitis effecting the posterior segment of the eye to support the effectiveness and safety of the implant for up to 3 years in both randomised controlled trials and real-world practices. Conclusions: Data showed that over a 36 month period, treatment with the fluocinolone acetonide intravitreal implant was associated with significantly fewer episodes of uveitic recurrence, a significantly longer time to uveitic recurrence, greater improvement in visual acuity, a lower need for adjunctive therapy, and an acceptable safety profile. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate changes in macular sensitivity, as measured with microperimetry, among patients with maculopathy and stable visual acuity (VA). Methods: Macular sensitivity was assessed using the Spectral OCT/SLO™ microperimetry (OCT/SLO, Optos Plc., Dunfermline, UK) in 25 eyes (16 patients) with maculopathy and stable VA (<5 letters change in ETDRS score) at two consecutive clinic visits. To take the limits of the test-retest repeatability of the OCT/SLO into account, coefficient of repeatability (CoR) was employed to estimate the probability of the sensitivity changes being secondary to measurement noise. Results: The point sensitivity changes were statistically significant (Wilcoxon signed-rank test, P < 0.001). Seventy-seven points (11 %) out of a total of 700 sensitivity points had a genuine sensitivity change, with a mean increase of 8.6 ± 2.6 dB in 35 points and a mean decrease of 7.9 ± 2.2 dB in 42 points. Conclusions: Point-to-point change in macular sensitivity can be used as a biomarker of changes in disease activity in patients with maculopathy, and can be more accurate than either mean sensitivity or BCVA in detection of changes in macular function. The measurement variability should be considered when observing the local sensitivity changes. [ABSTRACT FROM AUTHOR]

Purpose: To report 36-month outcomes of RIDE (NCT00473382) and RISE (NCT00473330), trials of ranibizumab in diabetic macular edema (DME). Design: Phase III, randomized, multicenter, double-masked, 3-year trials, sham injection–controlled for 2 years. Participants: Adults with DME (n=759), baseline best-corrected visual acuity (BCVA) 20/40 to 20/320 Snellen equivalent, and central foveal thickness (CFT) ≥275 μm on optical coherence tomography. Methods: Patients were randomized equally (1 eye per patient) to monthly 0.5 mg or 0.3 mg ranibizumab or sham injection. In the third year, sham patients, while still masked, were eligible to cross over to monthly 0.5 mg ranibizumab. Macular laser was available to all patients starting at month 3; panretinal laser was available as necessary. Main Outcome Measures: The proportion of patients gaining ≥15 Early Treatment Diabetic Retinopathy Study letters in BCVA from baseline at month 24. Results: Visual acuity (VA) outcomes seen at month 24 in ranibizumab groups were consistent through month 36; the proportions of patients who gained ≥15 letters from baseline at month 36 in the sham/0.5 mg, 0.3 mg, and 0.5 mg ranibizumab groups were 19.2%, 36.8%, and 40.2%, respectively, in RIDE and 22.0%, 51.2%, and 41.6%, respectively, in RISE. In the ranibizumab arms, reductions in CFT seen at 24 months were, on average, sustained through month 36. After crossover to 1 year of treatment with ranibizumab, average VA gains in the sham/0.5 mg group were lower compared with gains seen in the ranibizumab patients after 1 year of treatment (2.8 vs. 10.6 and 11.1 letters). Per-injection rates of endophthalmitis remained low over time (∼0.06% per injection). The incidence of serious adverse events potentially related to systemic vascular endothelial growth factor inhibition was 19.7% in patients who received 0.5 mg ranibizumab compared with 16.8% in the 0.3 mg group. Conclusions: The strong VA gains and improvement in retinal anatomy achieved with ranibizumab at month 24 were sustained through month 36. Delayed treatment in patients receiving sham treatment did not seem to result in the same extent of VA improvement observed in patients originally randomized to ranibizumab. Ocular and systemic safety was generally consistent with the results seen at month 24. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Purpose: To compare different doses and dosing regimens of Vascular Endothelial Growth Factor (VEGF) Trap-Eye with laser photocoagulation in eyes with diabetic macular edema (DME). Design: Randomized, double-masked, multicenter, phase 2 clinical trial. Participants: Diabetic patients (n = 221) with center-involved DME. Methods: Participants were assigned randomly to 1 of 5 treatment regimens: VEGF Trap-Eye 0.5 mg every 4 weeks (0.5q4); 2 mg every 4 weeks (2q4); 2 mg every 8 weeks after 3 initial monthly doses (2q8); or 2 mg dosing as needed after 3 initial monthly doses (2PRN), or macular laser photocoagulation. Main Outcome Measures: The change in best-corrected visual acuity (BCVA) at 24 weeks (the primary end point) and at 52 weeks, proportion of eyes that gained 15 letters or more in Early Treatment of Diabetic Retinopathy Study (ETDRS) BCVA, and mean changes in central retinal thickness (CRT) from baseline. Results: As previously reported, mean improvements in BCVA in the VEGF Trap-Eye groups at week 24 were 8.6, 11.4, 8.5, and 10.3 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus 2.5 letters for the laser group (P ≤ 0.0085 versus laser). Mean improvements in BCVA in the VEGF Trap-Eye groups at week 52 were 11.0, 13.1, 9.7, and 12.0 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus −1.3 letters for the laser group (P ≤ 0.0001 versus laser). Proportions of eyes with gains in BCVA of 15 or more ETDRS letters at week 52 in the VEGF Trap-Eye groups were 40.9%, 45.5%, 23.8%, and 42.2% versus 11.4% for laser (P = 0.0031, P = 0.0007, P = 0.1608, and P = 0.0016, respectively, versus laser). Mean reductions in CRT in the VEGF Trap-Eye groups at week 52 were −165.4 μm, −227.4 μm, −187.8 μm, and −180.3 μm versus −58.4 μm for laser (P < 0.0001 versus laser). Vascular Endothelial Growth Factor Trap-Eye generally was well tolerated. The most frequent ocular adverse events with VEGF Trap-Eye were conjunctival hemorrhage, eye pain, ocular hyperemia, and increased intraocular pressure, whereas common systemic adverse events included hypertension, nausea, and congestive heart failure. Conclusions: Significant gains in BCVA from baseline achieved at week 24 were maintained or improved at week 52 in all VEGF Trap-Eye groups. Vascular Endothelial Growth Factor Trap-Eye warrants further investigation for the treatment of DME. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Purpose: To describe visual acuity (VA) and inflammation following cataract surgery in eyes with noninfectious posterior uveitis (NIPU) that were being treated with a fluocinolone acetonide (FA) intravitreal implant compared with those that were not. Design: Post hoc, subgroup analysis of data from a 3-year, dose-masked, randomized, multicenter trial evaluating the FA implant for the treatment of NIPU. Participants and controls: The subset of eyes that underwent cataract surgery during the 3-year trial. Eyes were either implanted with a 0.59- or a 2.1-mg FA implant, or, in the case of affected fellow eyes, received standard-of-care local treatment. Main outcome measures: VA, anterior and posterior chamber inflammation at 1 and 3 months after surgery, and rate of uveitis recurrence and serious postoperative ocular adverse events. Results: Of 278 patients enrolled in the main trial, 132/142 phakic implanted eyes and 39/186 phakic non-implanted eyes underwent cataract surgery. Mean improvement in VA was significantly greater in implanted than non-implanted eyes at 1 (P = 0.0047) and 3 months (P = 0.0015) postoperatively; significantly fewer anterior chamber cells were seen in implanted than nonimplanted eyes at 1 (P = 0.0084) and 3 months (P = 0.0002). Severity of vitreous haze was less in implanted than non-implanted eyes at 3 months postoperatively (P = 0.0005). The postsurgical uveitis recurrence rate was lower in implanted than non-implanted eyes (26.5% vs 44.4%; P = 0.0433). Glaucoma was reported in 19.7% of implanted eyes and no non-implanted eyes (P = 0.0008) postoperatively. Conclusion: In this post hoc subgroup analysis, eyes with NIPU treated with the FA intravitreal implant demonstrated better vision and less intraocular inflammation following cataract surgery than non-implanted eyes. Recurrent uveitic inflammation did not appear to be triggered by cataract surgery. Glaucoma occurred more frequently in implanted eyes. [ABSTRACT FROM AUTHOR]

Objectives: To determine the long-term effects of ranibizumab (RBZ) in patients with diabetic macular edema (DME). Design: Prospective, randomized, interventional, multicenter clinical trial. Participants: One hundred twenty-six patients with DME. Methods: Subjects were randomized 1:1:1 to receive 0.5 mg RBZ at baseline and months 1, 3, and 5 (group 1), focal or grid laser photocoagulation at baseline and month 3 if needed (group 2), or a combination of 0.5 mg RBZ and focal or grid laser at baseline and month 3 (group 3). Starting at month 6, if retreatment criteria were met, all subjects could be treated with RBZ. Main Outcome Measures: The mean change from baseline in best-corrected visual acuity (BCVA) at month 24. Results: After the primary end point at month 6, most patients in all groups were treated only with RBZ, and the mean number of injections was 5.3, 4.4, and 2.9 during the 18-month follow-up period in groups 1, 2, and 3, respectively. For the 33 patients in group 1, 34 patients in group 2, and 34 patients in group 3 who remained in the study through 24 months, the mean improvement in BCVA was 7.4, 0.5, and 3.8 letters at the 6-month primary end point, compared with 7.7, 5.1, and 6.8 letters at month 24, and the percentage of patients who gained 3 lines or more of BCVA was 21, 0, and 6 at month 6, compared with 24, 18, and 26 at month 24. The percentage of patients with 20/40 or better Snellen equivalent at month 24 was 45% in group 1, 44% in group 2, and 35% in group 3. Mean foveal thickness (FTH), defined as center subfield thickness, at month 24 was 340 μm, 286 μm, and 258 μm for groups 1, 2, and 3, respectively, and the percentage of patients with center subfield thickness of 250 μm or less was 36%, 47%, and 68%, respectively. Conclusions: Intraocular injections of RBZ provided benefit for patients with DME for at least 2 years, and when combined with focal or grid laser treatments, the amount of residual edema was reduced, as were the frequency of injections needed to control edema. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Purpose: To investigate the safety, tolerability, and bioactivity of intravenous infusions of bevacizumab in patients with choroidal neovascularization (CNV) attributable to causes other than age-related macular degeneration.Design: Nonrandomized clinical trial.Methods: Ten patients with CNV received infusions of 5 mg/kg of bevacizumab. The primary efficacy outcome measure was change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study letters read at 4 meters) at 24 weeks and secondary measures were changes from baseline in excess foveal thickness (center subfield thickness), area of fluorescein leakage, and area of CNV.Results: Infusions were well tolerated and there were no ocular or systemic adverse events. At baseline, median VA was 25.5 letters read at 4 meters (20/80) and median foveal thickness was 346 mum. At the primary endpoint (24 weeks), median VA was 48.5 letters (20/32), representing four lines of improvement from baseline (P = .005), median foveal thickness was 248 mum representing a 72% reduction in excess foveal thickness (P = .007). Four of nine patients had complete elimination of fluorescein leakage, three had near complete elimination (reductions of 91%, 88%, and 87%), two had modest reductions, and one had no reduction. All patients except one showed a reduction in area of CNV with a median reduction of 43%.Conclusions: Despite the small number of patients studied, the marked improvement in VA accompanied by prominent reductions in foveal thickness, fluorescein leakage, and area of CNV suggest a beneficial effect. It may be worthwhile to consider further evaluation of systemic bevacizumab in young patients with CNV. [ABSTRACT FROM AUTHOR]

Purpose: The role of vascular endothelial growth factor (VEGF) in diabetic macular edema (DME) was tested with ranibizumab, a specific antagonist of VEGF. Design: A nonrandomized clinical trial. Methods: Ten patients with chronic DME received intraocular injections of 0.5 mg of ranibizumab at baseline and at one, two, four, and six months. The primary outcome was change in foveal thickness between baseline and seven months, and the secondary outcome measures were changes from baseline in visual acuity and macular volume. Results: Mean values at baseline were 503 μm for foveal thickness, 9.22 mm3 for macular volume, and 28.1 letters (20/80) read on an Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart. At seven months (one month after the fifth injection), the mean foveal thickness was 257 μm, which was a reduction of 246 μm (85% of the excess foveal thickness present at baseline; P = .005 by Wilcoxon signed-rank test for likelihood that this change is due to ranibizumab rather than chance). The macular volume was 7.47 mm3, which was a reduction of 1.75 mm3 (77% of the excess macular volume at baseline; P = .009). Mean visual acuity was 40.4 letters (20/40), which was an improvement of 12.3 letters (P = .005). The injections were well-tolerated with no ocular or systemic adverse events. Conclusion: Intraocular injections of ranibizumab significantly reduced foveal thickness and improved visual acuity in 10 patients with DME, which demonstrated that VEGF is an important therapeutic target for DME. A randomized, controlled, double-masked trial is needed to test whether intraocular injections of ranibizumab provide long-term benefit to patients with DME. [Copyright &y& Elsevier]

We report the clinical course and pathologic findings in a case of intraocular sclerosing inflammatory pseudotumor in a 21-year-old man. The patient initially had a unilateral right interstitial keratitis, scleritis, uveitis, ciliary body mass, and retinal detachment. Scleral and vitreous biopsy specimens revealed an inflammatory process. The eye was eventually enucleated despite therapy with high doses of prednisone and ciprofloxacin hydrochloride. Histologic examination of the globe showed nongranulomatous, acute (neutrophils) and chronic (lymphocytes and histiocytes) inflammation with proliferation of fibrous tissue within the vitreous cavity, uvea, sclera, and contiguous orbital fibroadipose tissue. The contralateral eye later developed a similar mass that resolved following aggressive and prolonged immunosuppressive therapy with retention of 20/16 visual acuity. [ABSTRACT FROM AUTHOR]

Purpose: To report a case of intraocular non-Hodgkin lymphoma (NHL) manifesting as persistent intermediate uveitis, facial mass, and Bell palsy. Design: Retrospective, interventional case report. Methods: A 51-year-old patient with persistent intermediate uveitis for 4 years is diagnosed with intraocular NHL after developing Bell palsy and a facial mass. Initial diagnostic vitrectomy was inconclusive. Results: Subsequent treatment with cyclophosphamide, adriamycin, vincristine, prednisone, and rituximab resulted in regressed facial mass and improved visual acuity. Conclusion: NHL can manifest as latent Bell palsy and facial mass in addition to the more common symptoms of uveitis. Intraocular NHL should be suspected in any patient of any age with persistent uveitis. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of intravitreal sirolimus in the management of noninfectious uveitis of the posterior segment (NIU-PS). Combined analysis of 2 phase 3, randomized, double-masked, multinational, 6-month studies. Adults with active NIU-PS (intermediate uveitis, posterior uveitis, or panuveitis; defined as vitreous haze [VH] ≥1.5+ on modified Standardization of Uveitis Nomenclature scale). Patients were randomized 1:1:1 to receive intravitreal sirolimus 44 μg (n = 208), 440 μg (n = 208), or 880 μg (n = 177) on days 1, 60, and 120. Patients discontinued medications for NIU-PS except for systemic corticosteroids, which were tapered according to protocol. Enrollment in the 880-μg group was terminated after interim results found no significant difference in efficacy compared with the 440-μg dose. The primary efficacy end point was the percentage of patients with VH of 0 at month 5 in the study eye without the use of rescue therapy. Secondary efficacy end points included VH of 0 or 0.5+, corticosteroid-tapering success, and changes in best-corrected visual acuity (BCVA). Safety measures included ocular and nonocular adverse events. A total of 592 patients were randomized. Significantly higher proportions of patients treated with 440 μg compared with 44 μg intravitreal sirolimus achieved VH of 0 (21.2% vs. 13.5%; P = 0.038) and VH of 0 or 0.5+ (50.0% vs. 40.4%; P = 0.049) at month 5. Best-corrected visual acuity was stable (absolute change <5 ETDRS letters) or improved >5 letters in 80.1% and 80.2% of patients in the 440-μg and 44-μg groups, respectively. At month 5, corticosteroids were tapered successfully in 69.6% and 68.8% of patients in the 440-μg and 44-μg groups, and among these patients, VH of 0 or 0.5+ was achieved by 43.5% and 28.1% in the 440-μg and 44-μg groups. Both doses were generally well tolerated. Mean changes from baseline intraocular pressure (IOP) in the study eye at each analysis visit were minimal in all treatment groups. Intravitreal sirolimus 440 μg improved ocular inflammation, as measured by VH, compared with the 44-μg dose, with minimal impact on IOP, while preserving BCVA. [ABSTRACT FROM AUTHOR]

Purpose To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. Design Phase 3, open-label, multicenter clinical trial extension (VISUAL III). Participants Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. Methods Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. Main Outcome Measures Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. Results Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5–1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. Conclusions Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified. [ABSTRACT FROM AUTHOR]

Purpose To compare 2.0 mg ranibizumab (RBZ) injections with 0.5 mg RBZ for eyes with center-involved diabetic macular edema (DME). Design Randomized, controlled, double-masked (to the dose), interventional, multicenter clinical trial. Participants A total of 152 patients (152 eyes) with DME. Methods Eligible eyes were randomized in a 1:1 ratio to 0.5 mg (n = 77) or 2.0 mg (n = 75) RBZ. Study eyes received 6 monthly mandatory injections followed by as-needed injections until month 24. Main Outcome Measures The primary efficacy end point of the study was mean change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) at month 6. Secondary outcomes included the mean change in BCVA and CFT at month 24, and incidence and severity of systemic and ocular adverse events through month 24. Results A total of 152 eyes were randomized in the study. At month 24, the mean improvement from baseline BCVA was +11.06 letters in the 0.5 mg RBZ group (n = 59) and +6.78 letters in the 2.0 mg RBZ group (n = 54) ( P = 0.02). The mean numbers of RBZ injections through month 24 were 18.4 and 17.3 in the 0.5 mg and 2.0 mg RBZ groups, respectively ( P = 0.08). The mean change in CFT was −192.53 μm in the 0.5 mg RBZ group and −170.64 μm in the 2.0 mg RBZ group ( P = 0.41). By month 24, 3 deaths had occurred in the 0.5 mg RBZ group and 3 deaths had occurred in the 2.0 mg RBZ group; 5 of these 6 deaths occurred secondary to cardiovascular causes, and 1 death occurred as the result of severe pneumonia. All 5 patients with a cardiovascular cause of death had a history of coronary heart disease. Conclusions At month 24, there were significant visual and anatomic improvements in both groups, with subjects in the 0.5 mg RBZ group gaining more vision. Visual and anatomic gains achieved at month 6 were largely maintained through month 24. No new safety events were identified. In this study population, 2.0 mg RBZ does not appear to provide additional benefit over 0.5 mg RBZ. [ABSTRACT FROM AUTHOR]

Purpose To assess the role of vitreomacular adhesion (VMA) in visual and anatomic outcomes in patients with diabetic macular edema (DME). Design Retrospective cohort study. Participants Data from patients enrolled in the Ranibizumab for Edema of the Macula in Diabetes: Protocol 3 with High Dose (READ-3) study were analyzed. Methods In the READ-3 study, patients with DME received monthly intravitreal injections of either 0.5 or 2.0 mg ranibizumab. Optical coherence tomography images from patients who completed the month 6 visit of the study were analyzed at the baseline visit to identify the presence (VMA+) or absence (VMA−) of VMA. Patients with any degree of vitreomacular traction were excluded from the analysis. Two independent graders graded all images. Vitreomacular adhesion was classified by size of adhesion into either focal (<1500 μm) or broad (≥1500 μm). Main Outcome Measures Mean changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) at month 6 and incidence of posterior vitreous detachment (PVD). Results One hundred fifty-two eyes (152 patients) were randomized in the READ-3 study. One hundred twenty-four eyes (124 patients) were eligible for the study based on study criteria. Twenty-eight eyes did not meet study criteria and were excluded from the study. At baseline, 26 patients were classified as VMA+ and 98 patients were classified as VMA−. The distribution of the 2 doses of ranibizumab (0.5 and 2.0 mg) in the 2 groups was similar. At month 6, the mean improvement in BCVA was 11.31±6.67 and 6.86±7.58 letters in the VMA+ and VMA− groups, respectively ( P = 0.007). Mean improvement in CRT was −173.81±132.31 and −161.84±131.34 μm in the VMA+ and VMA− groups, respectively ( P = 0.681). At month 6, among the 26 VMA+ eyes (at baseline), 7 eyes demonstrated PVD, 17 eyes showed no change in VMA status, and 2 eyes were not gradable and were excluded. Conclusions Diabetic macular edema patients with VMA have a greater potential for improvement in visual outcomes with anti–vascular endothelial growth factor therapy. Therefore, the presence of VMA should not preclude patients with DME from receiving treatment. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the biologic effects and safety of vascular endothelial growth factor (VEGF) Trap-Eye during a 12-week fixed-dosing period in patients with neovascular (wet) age-related macular degeneration (AMD). Design: Multicenter, prospective, randomized, double-masked clinical trial with initial 12-week fixed dosing period. Data were analyzed to week 16. Participants: We included 159 patients with subfoveal choroidal neovascularization secondary to wet AMD. Methods: Patients were randomized 1:1:1:1:1 to VEGF Trap-Eye during the fixed-dosing phase (day 1 to week 12): 0.5 or 2 mg every 4 weeks (0.5 mg q4wk, 2 mg q4wk) on day 1 and at weeks 4, 8, and 12; or 0.5, 2, or 4 mg every 12 weeks (0.5 mg q12wk, 2 mg q12wk, or 4 mg q12wk) on day 1 and at week 12. Main Outcome Measures: The primary endpoint was change from baseline in central retinal/lesion thickness (CR/LT) at week 12; secondary outcomes included change in best-corrected visual acuity (BCVA), proportion of patients with a gain of ≥15 letters, proportion of patients with a loss of >15 letters, and safety. Results: At week 12, treatment with VEGF Trap-Eye resulted in a significant mean decrease in CR/LT of 119 μm from baseline in all groups combined (P<0.0001). The reduction in CR/LT with the 2 mg q4wk and 0.5mg q4wk regimens was significantly greater than each of the quarterly dosing regimens. The BCVA increased significantly by a mean of 5.7 letters at 12 weeks in the combined group (P<0.0001), with the greatest mean gain of >8 letters in the monthly dosing groups. At 8 weeks, BCVA improvements were similar with 2 mg q4wk and 2 mg q12wk dosing. After the last required dose at week 12, CR/LT and visual acuity were maintained or further improved at week 16 in all treatment groups. Ocular adverse events were mild and consistent with safety profiles reported for other intraocular anti-VEGF treatments. Conclusions: Repeated monthly intravitreal dosing of VEGF Trap-Eye over 12 weeks demonstrated significant reductions in retinal thickness and improvements in visual acuity, and was well-tolerated in patients with neovascular AMD. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Purpose: To assess the safety, tolerability, pharmacokinetics, and dose-limiting toxicity of single intravitreal injection of Sirna-027, a small interfering RNA targeting vascular endothelial growth factor receptor-1, in patients with choroidal neovascularization (CNV) resulting from neovascular age-related macular degeneration (AMD). Secondary objectives included assessment of anatomic changes in retinal thickness, size of CNV, and changes in visual acuity. Design: Prospective, open-label, single-dose, dose-escalation phase 1 study. Methods: Twenty-six eyes of 26 patients with a median age of 82 years and CNV resulting from AMD who had previous treatments with other therapies were treated at 2 academic retinal practices. Patients received a single dose of Sirna-027 (100, 200, 400, 800, 1200, or 1600 μg/eye). Blood was sampled for pharmacokinetic analysis at 1, 4, and 24 hours after injection and on day 7. Patients underwent ophthalmic examinations including visual acuity, fluorescein angiography, and optical coherence tomography at screening and days 7, 14, 28, and 84. The main outcome measures were adverse reactions and dose-limiting toxicities. Results: Intravitreal injection of a single dose of Sirna-027 from 100 to 1600 μg was well tolerated in patients with AMD, with no dose-limiting toxicity found. Adverse events were mild to moderate in severity. Adjusted mean foveal thickness decreased within 2 weeks after study treatment. The decrease was most pronounced in the 100- and 200-μg doses. Conclusions: A single intravitreal dose of Sirna-027 up to 1600 μg/eye was well tolerated in patients with CNV resulting from neovascular AMD that had been refractory to other therapies. Stabilization or improvement in visual acuity and foveal thickness was observed. No dose-response or dose-limiting effects were noted. [Copyright &y& Elsevier]

Purpose: Stimulation of nicotinic acetylcholine (nACh) receptors on vascular endothelial cells promotes angiogenesis and vascular permeability in animal models. The safety and bioactivity of topical mecamylamine, an antagonist of nACh receptors, was tested in patients with diabetic macular edema. Design: A multicenter phase I/II clinical trial. Methods: Twenty-three patients with chronic diabetic macular edema received 1% mecamylamine topically twice daily for 12 weeks, the primary end point. Patients underwent safety assessments, measurement of best-corrected visual acuity (BCVA), and measurement of foveal thickness using optical coherence tomography at baseline, 1, 4, 8, 12, and 16 weeks. Results: Mecamylamine drops were well tolerated and there were no drug-related safety problems. Mean improvement in BCVA at 1, 4, 8, 12, and 16 weeks was 2.8, 1.9, 2.4, 0.8, and 3.1 letters, respectively. There was little change in mean excess foveal thickness. There was substantial heterogeneity in response, because 8 patients showed convincing improvement in BCVA, foveal thickness, or both, 9 patients showed equivocal or no substantial changes, and 4 patients showed worsening. Five patients showed a substantial improvement in BCVA, foveal thickness, or both between their last visit while receiving mecamylamine and 1 month after stopping mecamylamine. Conclusions: This study suggested that administration of topical mecamylamine, a nonspecific nACh receptor blocker, may have heterogeneous effects in patients with diabetic macular edema. Variable expression of nACh receptor subtypes on endothelial cells that have different effects on permeability would provide an explanation for these results and should be investigated, because more specific nACh receptor blockers may dissociate antipermeability and propermeability effects. [Copyright &y& Elsevier]