Objective: To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment. Design: Multicenter, randomized clinical trial. Participants: Patients (n = 1107) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial. Interventions: At enrollment, patients were assigned to 4 treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment. Main Outcome Measures: Mean change in visual acuity. Results: Among patients following the same regimen for 2 years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, -1.4 letters; 95% confidence interval [CI], -3.7 to 0.8; P = 0.21). Mean gain was greater for monthly than for as-needed treatment (difference, -2.4 letters; 95% CI, -4.8 to -0.1; P = 0.046). The proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, P = 0.0003; regimen, P < 0.0001). Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2 (-2.2 letters; P = 0.03) and a lower proportion without fluid (-19%; P < 0.0001). Rates of death and arteriothrombotic events were similar for both drugs (P > 0.60). The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07-1.57; P = 0.009). Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF). Conclusions: Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF. (C) 2012 by the American Academy of Ophthalmology.

Importance Recent reports suggest that cilioretinal arteries (CRAs) confer protection against developing advanced age-related macular degeneration (AMD). Objective To further characterize the association between the presence of a CRA and incidence of geographic atrophy (GA) or choroidal neovascularization (CNV). Design This cohort study constituted an ad hoc secondary analysis of data from the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and was performed at 44 clinical centers in the United States among participants in CATT with CNV in the study eye and without advanced AMD in the fellow eye at baseline. The presence of a CRA was determined by 2 graders, masked to clinical data, using color fundus photographs, red-free fundus photographs, and fluorescein angiography. The proportion with CRAs at baseline between the study eye with CNV and fellow eye without CNV was first compared. The association of a CRA with incidence of CNV or GA at 5 years among fellow eyes and with incidence of GA among study (treated) eyes was then assessed. In addition, the association of CRAs with the Age-Related Eye Disease Study severity scale among the fellow eyes at baseline was assessed. Data were collected from February 1, 2008, through April 30, 2015, and analyzed from July 1, 2018, through April 30, 2019. Exposures Presence of a CRA. Main Outcomes and Measures The association between the presence of a CRA and incidence of CNV or GA at 5 years of follow-up. Results A total of 350 patients (700 eyes) (230 [65.7% women; mean [SD] age, 77 [7.2] years) were included in the analysis. Cilioretinal arteries were present in 67 of 345 (19.4%) fellow eyes without baseline CNV and 73 of 349 (20.9%) study eyes with baseline CNV (P = .60). Cilioretinal arteries in fellow eyes were not associated with incidence of CNV at 5 years (125 of 278 [45.0%] among eyes without CRAs and 30 of 67 [44.8%] among eyes with CRAs; P = .99) or with incidence of GA at 5 years (110 of 278 [39.6%] among eyes without CRAs and 25 of 67 [37.3%] among eyes with CRAs; P = .89). Cilioretinal arteries in study eyes were not associated with incidence of GA at 5 years (105 of 276 [38.0%] study eyes without CRAs and 26 of 73 [35.6%] study eyes with CRAs; P = .72). Conclusions and Relevance The analysis did not find a protective association between CRAs and incidence of CNV or GA among CATT participants who had unilateral exudative AMD. Why these findings were different from those of previous publications is unclear but may be partially explained by the different techniques used to detect CRAs or by the baseline advanced disease in CATT participants. Trial Registration ClinicalTrials.gov identifier: NCT00593450.

PURPOSE:To describe risk factors for scar formation and changes to fibrotic scar through 5 years in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). DESIGN:Multicenter, prospective cohort study. PARTICIPANTS:A total of 1061 subjects in CATT. METHODS:Color photographic and fluorescein angiographic images from baseline and 1, 2, and 5 years were evaluated. Incidence of scar formation was estimated with Kaplan-Meier curves. Risk factors were assessed with Cox regression models. MAIN OUTCOME MEASURES:Scar formation, fibrotic scar area, and macular atrophy associated with fibrotic scar ("atrophy"). RESULTS:Cumulative proportion of eyes with scar was 32%, 46%, and 56% at years 1, 2, and 5, respectively. Baseline factors associated with increased risk (adjusted hazards ratio [aHR] and 95% confidence interval [CI]) were classic choroidal neovascularization (CNV) (aHR, 4.49; 95% CI, 3.34-6.04) versus occult, hemorrhage >1 disc area (DA) (aHR, 2.28; 95% CI, 1.49-3.47) versus no hemorrhage, retinal thickness >212 μm (aHR, 2.58; 95% CI, 1.69-3.94) versus <120 μm, subretinal tissue complex thickness >275 μm (aHR, 2.64; 95% CI, 1.81-3.84) versus ≤75 μm, subretinal fluid thickness >25 μm (aHR, 1.31; 95% CI, 0.97-1.75) versus no fluid, visual acuity (VA) in fellow eye 20/20 (aHR, 1.72; 95% CI, 1.25-2.36) versus 20/50 or worse, retinal pigment epithelium elevation absence (aHR, 1.71; 95% CI, 1.21-2.41), and subretinal hyperreflective material (aHR, 1.72; 95% CI, 1.25-2.36). Among 68 eyes that developed fibrotic scar at year 1, VA decreased by a mean of additional 13 letters between years 1 and 5. Mean scar area was 1.2, 1.2, and 1.9 DA at 1, 2, and 5 years, respectively. Atrophy was present in 18%, 24%, and 54% of these eyes at years 1, 2, and 5, respectively; the mean areas were 1.6, 2.0, and 3.1 DA, respectively. Atrophy replaced fibrotic scar in 8 eyes at year 5. There was no significant correlation between scar growth and atrophy growth. The rate of growth for both was similar between the clinical trial and observation periods. CONCLUSIONS:Several morphologic features, including classic CNV and large hemorrhage, are associated with scar formation. Rate of new scar formation declined after 2 years. Most fibrotic scars and accompanying macular atrophy expanded over time, reducing VA.

Purpose: To study new and existing risk factors related to age-related macular degeneration (AMD) phenotypes in a Colorado cohort. Methods: Age-related macular degeneration was categorized into early, intermediate, or advanced forms. Controls (n = 180) were patients with cataract and no AMD. Demographic and clinical data were gathered by patient interview and verified by chart review. Image data were reviewed by vitreoretinal specialists. Statistical analysis included univariable and multivariate logistic regression analysis (P < 0.05). Results: Among the 456 patients with AMD, 157 (34.4%), 80 (17.6%), and 219 (48.0%) had the early/intermediate, geographic atrophy, and neovascular forms of the disease, respectively. Adjusted for age, African-American race was associated with a reduced risk of early/intermediate (adjusted odds ratio [AOR] = 0.08, confidence interval [CI] = 0.01-0.67) and neovascular AMD (AOR = 0.15, CI = 0.03-0.72). A family history of AMD was a risk factor for early/intermediate (AOR = 4.08, CI = 2.30-7.25), geographic atrophy (AOR = 8.62, CI = 3.77-19.7), and neovascular AMD (AOR = 3.76, CI = 2.16-6.56). A history of asthma was related to the early/intermediate form of AMD (AOR = 2.34, CI = 1.22-4.46). Conclusion: Studying AMD in specific populations may reveal novel risk factors such as our finding of a relationship between asthma history and AMD.

Measurement of the evolution of both active galactic nuclei (AGN) and star-formation in galaxies underpins our understanding of galaxy evolution over cosmic time. Radio continuum observations can provide key information on these two processes, in particular via the mechanical feedback produced by radio jets in AGN, and via an unbiased dust-independent measurement of star formation rates. In this paper, we determine radio luminosity functions at 325 MHz for a sample of AGN and star-forming galaxies by matching a 138 deg(2) radio survey conducted with the Giant Metrewave Radio Telescope, with optical imaging and redshifts from the Galaxy And Mass Assembly survey. We find that the radio luminosity function at 325 MHz for star-forming galaxies closely follows that measured at 1.4 GHz. By fitting the AGN radio luminosity function out to z = 0.5 as a double power law, and parametrizing the evolution as Phi proportional to(1 + z)(k), we find evolution parameters of k = 0.92 +/- 0.95 assuming pure density evolution and k = 2.13 +/- 1.96 assuming pure luminosity evolution. We find that the Low Excitation Radio Galaxies are the dominant population in space density at lower luminosities. Comparing our 325 MHz observations with radio continuum imaging at 1.4 GHz, we determine separate radio luminosity functions for steep-and flat-spectrum AGN, and show that the beamed population of flat-spectrum sources in our sample can be shifted in number density and luminosity to coincide with the unbeamed population of steep-spectrum sources, as is expected in the orientation-based unification of AGN.

We were challenged and delighted when Dr. Sharon Solomon, guest editor of this Retina Supplement, invited us to reminisce about caring for patients with common retinal disorders before there was access to the diagnostic and therapeutic tools that are readily available today. We agreed to confine our remarks to 3 common, but serious, conditions: age-related macular degeneration (Dr. Fine), diabetic retinopathy (Dr. Goldberg), and retinal detachment (Dr. Tasman). Each of us completed our ophthalmology training about half a century ago. At that time, a patient who received any 1 of the 3 diagnoses was at considerable risk of severe and irreversible loss of vision. Most readers today will have little if any experience in evaluating and treating such patients without access to a plethora of diagnostic and therapeutic technologies, including intravenous fluorescein angiography, laser photocoagulation, optical coherence tomography, ophthalmic ultrasound, angioinhibitory drugs, vitrectomy, intraocular gases, and many others. We are both pleased and privileged that each of us has practiced our profession long enough to enjoy what the enormous technological developments of the past half century, as described in this article, have meant for our patients. (C) 2016 by the American Academy of Ophthalmology.

Purpose: To describe outcomes 5 years after initiating treatment with bevacizumab or ranibizumab for neovascular age-related macular degeneration (AMD).Design: Cohort study.Participants: Patients enrolled in the Comparison of AMD Treatments Trials.Methods: Patients were assigned randomly to ranibizumab or bevacizumab and to 1 of 3 dosing regimens. After 2 years, patients were released from the clinical trial protocol. At 5 years, patients were recalled for examination.Main Outcome Measures: Visual acuity (VA) and morphologic retinal features.Results: Visual acuity was obtained for 647 of 914 (71%) living patients with average follow-up of 5.5 years. The mean number of examinations for AMD care after the clinical trial ended was 25.3, and the mean number of treatments was 15.4. Most patients (60%) were treated 1 time or more with a drug other than their assigned drug. At the 5-year visit, 50% of eyes had VA of 20/40 or better and 20% had VA of 20/200 or worse. Mean change in VA was -3 letters from baseline and -11 letters from 2 years. Among 467 eyes with fluorescein angiography, mean total lesion area was 12.9 mm(2), a mean of 4.8 mm(2) larger than at 2 years. Geographic atrophy was present in 213 of 515 (41%) gradable eyes and was subfoveal in 85 eyes (17%). Among 555 eyes with spectral-domain optical coherence tomography, 83% had fluid (61% intraretinal, 38% subretinal, and 36% suberetinal pigment epithelium). Mean foveal total thickness was 278 mm, a decrease of 182 mm from baseline and 20 mm from 2 years. The retina was abnormally thin (<120 mm) in 36% of eyes. Between 2 and 5 years, the group originally assigned to ranibizumab for 2 years lost more VA than the bevacizumab group (-4 letters; P = 0.008). Otherwise, there were no statistically significant differences in VA or morphologic outcomes between drug or regimen groups.Conclusions: Vision gains during the first 2 years were not maintained at 5 years. However, 50% of eyes had VA of 20/40 or better, confirming antievascular endothelial growth factor therapy as a major long-term therapeutic advance for neovascular AMD. (C) 2016 by the American Academy of Ophthalmology.

Objective: To compare baseline characteristics, treatment frequency, visual acuity (VA), and morphologic outcomes of eyes with >50% of the lesion composed of blood (B50 group) versus all other eyes (Other group) enrolled in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).Design: Prospective cohort study within a multicenter randomized clinical trial.Participants: CATT patients with neovascular age-related macular degeneration (AMD).Methods: Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different dosing regimens over a 2-year period. Reading center graders evaluated baseline and follow-up morphology in color fundus photographs, fluorescein angiography (FA), and optical coherence tomography (OCT). Masked examiners tested VA.Main Outcome Measures: Morphologic features and VA at 1 and 2 years.Results: The B50 group consisted of 84 of 1185 (7.1%) patients enrolled in CATT. Baseline lesion characteristics differed between groups. In the B50 group, choroidal neovascularization size was smaller (0.73 vs 1.83 disc areas [DA]; P < 0.001), total lesion size was greater (4.55 vs 2.31 DA; P < 0.001), total retinal thickness was greater (524 vs 455 mm; P = 0.02), and mean VA was worse (56.0 vs 60.9 letters; P = 0.002). Increases in mean VA were similar in the B50 and Other groups at 1 year (+9.3 vs +7.2 letters; P = 0.22) and at 2 years (9.0 vs 6.1 letters; P = 0.17). Eyes treated PRN received a similar number of injections in the 2 groups (12.2 vs 13.4; P = 0.27). Mean lesion size in the B50 group decreased by 1.2 DA at both 1 and 2 years (primarily owing to resolution of hemorrhage) and increased in the Other group by 0.33 DA at 1 year and 0.91 DA at 2 years (P < 0.001). Leakage on FA and fluid on OCT were similar between groups at 1 and 2 years.Conclusions: In CATT, the B50 group had a visual prognosis similar to the Other group. Lesion size decreased markedly through 2 years. Eyes like those enrolled in CATT with neovascular AMD lesions composed of >50% blood can be managed similarly to those with less or no blood. (C) 2015 by the American Academy of Ophthalmology.

PURPOSE: To determine the relationship between delayed patchy choroidal filling and morphologic and functional outcomes among eyes treated with ranibizumab or bevacizumab.DESIGN: Cohort study.METHODS: Comparison of Age-related Macular Degeneration Treatment Trials participants were assigned randomly to ranibizumab or bevacizumab on a monthly or as-needed schedule. Presence of delayed patchy choroidal filling and morphologic and functional outcomes were evaluated among eyes with gradable fluorescein angiography at baseline (n = 973) and at 1 year (n = 860) eyes.RESULTS: Delayed filling was present in 75 (7.7%) of 973 eyes at baseline. Eyes with incident delayed filling at 1 year (23 [2.9%] of 798) showed a mean decrease of 1.7 letters in visual acuity, whereas eyes without incident delayed filling had a mean improvement of 8.1 letters (difference [Delta], -9.8; 95% confidence interval [CI], -15.8 to -3.9; P < .01). Eyes with incident delayed filling had a larger increase in mean total lesion area of choroidal neovascularization (3.00 mm(2)) than eyes without incident delayed filling (0.56 mm(2); Delta, 2.4; 95% CI, 0.4 to 4.4; P = .02). The proportion with incident delayed filling at 1 year was similar among eyes treated with ranibizumab (10 [2.4%] of 413) or bevacizumab (13 [3.3%] of 385; P = .53) and among eyes treated monthly (12 [3.1%] of 388) or as needed (11 [2.7%] of 410; P = .83).CONCLUSIONS: Delayed patchy choroidal filling was uncommon at baseline. Although only a small percentage of eyes demonstrated delayed filling during the first year of anti-vascular endothelial growth factor treatment, these eyes had worse visual acuity and a larger increase in total lesion area of choroidal neovascularization. (C) 2014 by Elsevier Inc. All rights reserved.

To collect health care resource utilization (HCRU) in the management of chronic lymphocytic leukemia (CLL) patients who have relapsed/refractory disease, and had at least one previous chemotherapy treatment. A retrospective, longitudinal, cohort study design is being used involving three cancer centres in Ontario, Canada. A convenience sample of 90 CLL patients was selected with inclusion criteria of adult age at diagnosis, date of diagnosis between January 1, 2006 to 2012, relapsed/refractory disease that required at least one previous therapy, and minimum of one oncology visit. Demographics and HCRU data were collected with descriptive statistics to be presented. Costs are in 2013 Canadian dollars. At the Juravinski Cancer Centre (Hamilton, Ontario), 30 CLL patients met the study inclusion criteria. 22 were male with the mean age at diagnosis being 65.2 years (range 41-86 years). 43% (13/30) of the interim cohort had genetic testing. 73.3% of patients (22/30) received fludarabine-based chemotherapy as first-line treatment. 13.6% (3/22) were re-treated with fludarabine as second-line treatment. 26.7% of patients (8/30) received chlorambucil as first-line treatment. Of those, 2 patients were re-treated with chlorambucil as second-line treatment, 4 received fludarabine-based chemotherapy, and 2 did not receive further treatment. 40% of patients (12/30) were given rituximab. 90% of patients who needed other medications utilized a mean number of 6.0 (0-15) drugs. Half of the cohort visited the emergency department a total of 19 times and experienced 25 adverse events. The total cost of diagnostic tests/procedures was $17,502, $28,895 for hospitalizations, and $49,794 for specialist visits. Preliminary results from one cancer centre indicate substantial HCRU associated with CLL management. The authors plan to complete data extraction at the two remaining cancer centres in order to determine HCRU and cost results for the full cohort.

PURPOSE:To address the most dynamic and current issues concerning today's treatment options and promising research efforts regarding treatment for age-related macular degeneration. This review is aimed to serve as a practical reference for more in-depth reviews on the subject.METHODS:An online review of the database PubMed and Ovid were performed, searching for the key words age-related macular degeneration, AMD, VEGF, treatment, PDT, steroids, bevacizumab, ranibizumab, VEGF-trap, radiation, combined therapy, as well as their compound phrases. The search was limited to articles published since 1985. All returned articles were carefully screened, and their references were manually reviewed for additional relevant data. The web page www.clinicaltrials.gov was also accessed in search of relevant research trials.RESULTS:A total of 363 articles were reviewed, including 64 additional articles extracted from the references. At the end, only 160 references were included in this review.CONCLUSION:Treatment for age-related macular degeneration is a very dynamic research field. While current treatments are mainly aimed at blocking vascular endothelial growth factor, future treatments seek to prevent vision loss because of scarring. Promising efforts have been made to address the dry form of the disease, which has lacked effective treatment.

Purpose: To address the most dynamic and current issues concerning human genetics, risk factors, pharmacoeconomics, and prevention regarding age-related macular degeneration. Methods: An online review of the database Pubmed and Ovid was performed, searching for the key words: age-related macular degeneration, AMD, pharmacoeconomics, risk factors, VEGF, prevention, genetics and their compound phrases. The search was limited to articles published since 1985 to date. All returned articles were carefully screened and their references were manually reviewed for additional relevant data. The webpage www.clinicaltrials.gov was also accessed in search of relevant research trials. Results: A total of 366 articles were reviewed, including 64 additional articles extracted from the references and 25 webpages and online databases from different institutions. At the end, only 244 references were included in this review. Conclusion: Age-related macular degeneration is a complex multifactorial disease that has an uneven manifestation around the world but with one common denominator, it is increasing and spreading. The economic burden that this disease poses in developed nations will increase in the coming years. Effective preventive therapies need to be developed in the near future.

BACKGROUND:Data on real-life utilization of granulocyte colony-stimulating factors (g-csfs) in Canada are limited. The objective of the present study was to describe the reasons for, and the patterns of, g-csf use in selected outpatient oncology clinics in Ontario and Quebec.METHODS:In a retrospective longitudinal cohort study, a review of medical records from 9 Canadian oncology clinics identified patients being prescribed filgrastim (fil) and pegfilgrastim (peg). Patient characteristics, reasons for g-csf use, and treatment patterns were descriptively analyzed.RESULTS:Medical records of 395 patients initiating g-csf therapy between January 2008 and January 2009 were included. Of this population, 80% were women, and breast cancer was the predominant diagnosis (59%). The most commonly prescribed g-csf was fil (56% in Ontario and 98% in Quebec). The most frequent reason for g-csf use was primary prophylaxis (42% for both fil and peg), followed by secondary prophylaxis (37% fil, 41% peg). Those proportions varied by tumour type and chemotherapy regimen. Delayed g-csf administration (more than 1 day after the end of chemotherapy) was frequently observed for fil, but rarely reported for peg, and that finding was consistent across tumours and concurrent chemotherapy regimens.CONCLUSIONS:The use of g-csf varies with the malignancy type and the provincial health care setting. The most commonly prescribed g-csf agent was fil, and most first g-csf prescriptions were for primary prophylaxis. Delays were frequently observed for patients receiving fil, but were rarely reported for those receiving peg.

Using a sample of 24264 optically selected AGNs from the SDSS DR7 database, we characterise how the profile of the [OIII] emission line relates to bolometric luminosity (L_Bol), Eddington ratio, radio loudness, radio luminosity (L_Rad) and optical class (Sy 1/2) to determine what drives the kinematics of this kpc-scale line emitting gas. Spectral stacking is used to characterise how the average [OIII] profile changes as a function of these variables. After accounting for the correlation between L_Bol and L_Rad, we report that L_Rad has the strongest influence on the [OIII] profile, with moderate radio luminosity AGNs (log(L_Rad)=23-25 W/Hz) having the broadest [OIII] profiles. When binned according to Eddington ratio, only AGNs in our highest bin (i.e., R_Edd>0.3) show any signs of having broadened [OIII] profiles, although the small numbers of such extreme AGNs mean we cannot rule out that other processes (e.g., radio jets) are responsible for this broadening. We find no significant difference between the [OIII] profiles of broad and narrow-line Seyfert 1s. The [OIII] profiles of Sy 1 and 2 AGNs show the same trends in terms of line width, but Sy 1 AGNs display a much stronger blue wing, which we interpret as evidence of outflowing ionised gas. Using multi-component line fitting we calculate the proportions of AGNs with broad [OIII] profiles, finding that moderate radio luminosity AGNs are roughly 5 times more likely to have extremely broad [OIII] lines (FWHM>1000km/s) compared to lower L_Rad AGNs. Our results are consistent with the most disturbed gas kinematics being induced by compact radio cores (rather than powerful radio jets), although broadened [OIII] lines are also present, but much rarer, in low L_Rad systems (<10^23 W/Hz). Our catalogue of multi-component fits is freely available as an online resource.