ABSTRACT
PURPOSE: To report the rates of postintravitreal injection (IVT) endophthalmitis with topical conjunctival application of various concentrations of povidone-iodine (PI), including no PI. METHODS: Retrospective chart review of patients receiving IVTs performed in a single practice between January 2011 and June 2016. Concentration of PI for all injections was recorded and cases of endophthalmitis identified and reviewed. RESULTS: A total of 35,060 IVTs in 1854 patients were included from the 5.5-year period. 29,281 injections were performed with standard 5% PI, 5,460 injections with diluted PI (3,731 with 2.5%, 1,673 with 1.25%, 56 with 0.625%), and 319 IVTs with no PI. Incidence of patient-reported PI sensitivity occurred in 15.9% of patients. Fourteen cases of endophthalmitis were identified: 12 in eyes that received 5% PI, one in an eye that received 1.25% PI, and one in an eye receiving no PI. The incidence of endophthalmitis was 0.04% for 5% PI, 0.02% for dilute PI, and 0.31% for no PI prophylaxis. All cases underwent prompt vitrectomy and had positive cultures for coagulase-negative Staphylococcus. CONCLUSION: Application of dilute PI solution to the conjunctiva at the time of IVT is an effective alternative to 5% PI for endophthalmitis prophylaxis in betadine-sensitive patients.
Subject(s)
Endophthalmitis/prevention & control , Eye Infections, Bacterial/prevention & control , Patient Comfort , Povidone-Iodine/pharmacology , Adult , Anti-Infective Agents, Local/pharmacology , Endophthalmitis/etiology , Eye Infections, Bacterial/etiology , Female , Humans , Intravitreal Injections/adverse effects , Male , Middle Aged , Retrospective StudiesABSTRACT
PURPOSE: To evaluate the responsiveness of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) in patients with diabetic macular edema using data from the RIDE and RISE trials. METHODS: Patients were randomized to monthly intravitreal ranibizumab 0.3 mg, 0.5 mg, or sham injections for 2 years. The NEI VFQ-25 was administered at baseline and at Months 6, 12, 18, and 24. The least-squares mean change in NEI VFQ-25 for ≥15 letters gained or lost was derived from analysis of covariance models. RESULTS: The mean improvement in NEI VFQ-25 composite score associated with a ≥15-letter gain in best-corrected visual acuity over 24 months was 9.0 (95% confidence interval, 6.3-11.7) points in RIDE and 7.1 (95% confidence interval, 4.7-9.6) points in RISE. In patients who lost ≥15 letters, the mean worsening in overall NEI VFQ-25 composite score was -6.6 (95% confidence interval, -13.6 to 0.5) in RIDE and -2.7 (95% confidence interval, -8.9 to 3.5) in RISE. CONCLUSION: This exploratory analysis of data from the RIDE and RISE studies supports the responsiveness of the NEI VFQ-25 to changes in best-corrected visual acuity over time in patients with diabetic macular edema.
Subject(s)
Diabetic Retinopathy/physiopathology , Macular Edema/physiopathology , Ranibizumab/administration & dosage , Surveys and Questionnaires , Visual Acuity , Angiogenesis Inhibitors/administration & dosage , Diabetic Retinopathy/complications , Diabetic Retinopathy/drug therapy , Female , Humans , Intravitreal Injections , Macular Edema/drug therapy , Macular Edema/etiology , Male , Middle Aged , National Eye Institute (U.S.) , Sickness Impact Profile , United StatesABSTRACT
PURPOSE: To report on long-term visual outcomes in patients receiving continuous fixed-interval dosing of anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (AMD). DESIGN: Single-practice retrospective chart review. PARTICIPANTS: One hundred nine eyes with exudative AMD receiving continuous fixed-interval dosing (every 4-8 weeks) of anti-VEGF therapy (ranibizumab, bevacizumab, or aflibercept) for at least 5 years. Eyes were excluded if they averaged fewer than 6.5 injections per year. METHODS: Snellen visual acuity was recorded at baseline and all subsequent injections. Changes from baseline were calculated at yearly intervals. MAIN OUTCOME MEASURES: The primary outcome measure was mean change in letter score at 5, 6, and 7 years; secondary outcomes included the percentage of patients with 20/40 vision or better at 7 years and the mean change in letter score at each yearly time point based on baseline visual grouping (20/40 or better, 20/50-20/100, 20/200 or worse). RESULTS: Forty-four, 75, and 109 patients with 7, 6, and 5 years, respectively, of continuous treatment were identified. Mean change in letter score at year 5 was +14.0 letters (P = 3.9 × 10(-9)), +12.2 letters at 6 years (P = 1.5 × 10(-7)), and +12.1 letters at 7 years (P = 3.8 × 10(-5)). Driving vision (20/40 or better) was achieved in 43.2% of treated eyes. Subanalysis revealed that the greatest visual gains at 5 and 7 years were seen in those patients with baseline visual acuity worse than 20/200 (+24.5 and +25.5 letters), followed by those with 20/50 to 20/100 vision (+6.7 and +6.9 letters), and finally those with 20/20 to 20/40 (+3.7 and +3.4 letters). Patients received an average of 10.5 injections per year. CONCLUSIONS: Continuous fixed-interval dosing of anti-VEGF therapy in patients with exudative AMD results in favorable long-term preservation out to 7 years, with vision stabilizing or improving in 93.2% of eyes. Additionally, 43.2% of patients maintained driving vision in the treatment eye at 7 years compared with 10.1% at baseline. Our data suggest better outcomes with continuous therapy over published results with sporadic, as-needed therapy.
Subject(s)
Angiogenesis Inhibitors/administration & dosage , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity/physiology , Wet Macular Degeneration/drug therapy , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Bevacizumab , Drug Combinations , Female , Fluorescein Angiography , Follow-Up Studies , Humans , Intravitreal Injections , Male , Ranibizumab , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Retrospective Studies , Tomography, Optical Coherence , Treatment Outcome , Wet Macular Degeneration/diagnosis , Wet Macular Degeneration/physiopathologyABSTRACT
OBJECTIVE: To examine the effects of intravitreal ranibizumab (Lucentis; Genentech, Inc., South San Francisco, CA) treatment on patient-reported vision-related function, as assessed by 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) scores, in patients with visual impairment secondary to center-involved diabetic macular edema (DME). DESIGN: Within 2 randomized, double-masked, phase 3 clinical trials (RIDE [A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema {ME} With Center Involvement Secondary to Diabetes Mellitus; NCT00473382] and RISE [A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema {ME} With Center Involvement Secondary to Diabetes Mellitus; NCT00473330]), the NEI VFQ-25 was administered at baseline and at the 6-, 12-, 18-, and 24-month follow-up visits. PARTICIPANTS: Three hundred eighty-two (100%) RIDE patients and 377 (100%) RISE patients. INTERVENTION: Patients were randomized 1:1:1 to monthly injections of intravitreal ranibizumab 0.3 or 0.5 mg or sham. Study participants could receive macular laser for DME from month 3 onward if specific criteria were met. MAIN OUTCOME MEASURES: Exploratory post hoc analysis of mean change from baseline in NEI VFQ-25 scores at 12 and 24 months. RESULTS: Across all treatment arms, 13% to 28% of enrolled eyes were the better-seeing eye. For all eyes in RIDE and RISE, the mean change in NEI VFQ-25 composite score improved more in ranibizumab-treated eyes at both the 12- and 24-month visits compared with sham treatment. For the better-seeing eyes at baseline, the mean change in composite score with 0.3 mg ranibizumab at the 24-month visit was 10.9 more (95% confidence interval [CI], 2.5-19.2) than sham for RIDE patients and 1.3 more (95% CI, -10.5 to 13.0) than sham for RISE patients. For the worse-seeing eyes at baseline, the mean change in composite score with 0.3 mg ranibizumab at the 24-month visit was 1.0 more (95% CI, -4.7 to 6.7) than sham for RIDE patients and 1.8 more (95% CI, -2.7 to 6.2) than sham for RISE patients. Similar results for most of these outcomes were seen with 0.5 mg ranibizumab. CONCLUSIONS: These phase 3 trials demonstrated that ranibizumab treatment for DME likely improves patient-reported vision-related function outcomes compared with sham, further supporting treatment of DME with ranibizumab.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Diabetic Retinopathy/drug therapy , Macular Edema/drug therapy , Adult , Aged , Aged, 80 and over , Diabetic Retinopathy/physiopathology , Double-Blind Method , Female , Humans , Intravitreal Injections , Macular Edema/physiopathology , Male , Middle Aged , Ranibizumab , Surveys and Questionnaires , Visual Acuity/physiology , Young AdultABSTRACT
PURPOSE: To quantify the burden of illness for incident branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) in a commercially insured working-age (commercial) and Medicare US population. METHODS: Retrospective cohort analysis of health care claims from 2003 through 2008 from commercial and Medicare patients with ≥2 outpatient diagnoses for BRVO or CRVO. The index date was the first retinal vein occlusion diagnosis. Patients with medical and pharmacy benefits were followed ≥1 year preindex and then between 1 year and 3 years postindex. Incidence and prevalence of retinal vein occlusion was determined. Burden of illness was compared with matched control subjects without retinal vein occlusion. RESULTS: The commercial sample comprised 1,188 CRVO and 2,252 BRVO cases, whereas the Medicare sample had 2,739 CRVO and 4,573 BRVO cases. Adjusted ratio of case-to-control, all-cause expenditures for commercial patients at 1 year and 3 years postindex were 1.88 and 1.68, respectively, for BRVO and 1.42 and 1.36, respectively, for CRVO. For Medicare patients, these were 1.29 and 1.13, respectively, for BRVO and 1.23 and 1.14, respectively, for CRVO. All comparisons were significant (P < 0.001). CONCLUSION: Health care utilization and expenditures for commercially insured working-age and Medicare patients with BRVO or CRVO were significantly greater than those for control subjects. Retinal vein occlusion development may be a marker for the increased severity of systemic vascular disease.
Subject(s)
For-Profit Insurance Plans/economics , Health Care Costs/statistics & numerical data , Medicare/economics , Retinal Vein Occlusion/economics , Adult , Case-Control Studies , Female , Health Services/statistics & numerical data , Humans , Incidence , Male , Medicare/statistics & numerical data , Middle Aged , Multivariate Analysis , Prevalence , Retinal Vein Occlusion/drug therapy , Retinal Vein Occlusion/epidemiology , Retrospective Studies , United States/epidemiologyABSTRACT
Background and Objectives: To determine the efficacy, durability, and safety of a single treatment with intravitreal ranibizumab plus peripheral scatter laser (RaScaL) in patients with diabetic macular edema associated with peripheral retinal nonperfusion on ultrawide-field fluorescein angiography (UWFA). Study Design: A 6-month, randomized, controlled, prospective phase I/II study of 30 treatment-naïve eyes of 22 patients (8 bilateral patients) with visual impairment secondary to diabetic macular edema associated with peripheral nonperfusion on UWFA. Patients were randomized to receive ranibizumab plus UWFA-guided peripheral scatter laser (n = 15) or triamcinolone acetonide plus macular laser (n = 15). Results: At 6 months, the RaScaL group patients had fewer recurrences warranting retreatment (33% vs. 80%, p < 0.003). Mean change in final visual acuity and central foveal thickness were not statistically significant between groups. Conclusion: This pilot study suggests the efficacy, safety and durability of the RaScaL treatment regimen in patients with diabetic macular edema associated with peripheral nonperfusion on UWFA. © 2014 S. Karger AG, Basel.
ABSTRACT
OBJECTIVE: To evaluate the 12-month efficacy and safety of intravitreal ranibizumab 0.5 mg and 2.0 mg administered monthly and on an as-needed (PRN) basis in treatment-naïve patients with subfoveal neovascular age-related macular degeneration (wet AMD). DESIGN: A 24-month, phase III, randomized, multicenter, double-masked, dose-response study. PARTICIPANTS: Patients aged ≥ 50 years with subfoveal wet AMD. METHODS: Patients (n = 1098) were randomized to receive ranibizumab 0.5 mg or 2.0 mg intravitreal injections administered monthly or on a PRN basis after 3 monthly loading doses. MAIN OUTCOME MEASURES: The primary efficacy end point was the mean change from baseline in best-corrected visual acuity (BCVA) at month 12. Key secondary end points included the mean number of ranibizumab injections, the mean change from baseline in central foveal thickness (CFT) over time, and the proportion of patients who gained ≥ 15 letters of BCVA. Unless otherwise specified, end point analyses were performed using the last-observation-carried-forward method to impute missing data. RESULTS: At month 12, the mean change from baseline in BCVA for the 4 groups was +10.1 letters (0.5 mg monthly), +8.2 letters (0.5 mg PRN), +9.2 letters (2.0 mg monthly), and +8.6 letters (2.0 mg PRN). The proportion of patients who gained ≥ 15 letters from baseline at month 12 in the 4 groups was 34.5%, 30.2%, 36.1%, and 33.0%, respectively. The mean change from baseline in CFT at month 12 in the 4 groups was -172.0 µm, -161.2 µm, -163.3 µm, and -172.4 µm, respectively. The mean number of injections was 7.7 and 6.9 for the 0.5-mg PRN and 2.0-mg PRN groups, respectively. Ocular and systemic safety profiles were consistent with previous ranibizumab trials in AMD and comparable between groups. CONCLUSIONS: At month 12, the ranibizumab 2.0 mg monthly group did not meet the prespecified superiority comparison and the ranibizumab 0.5 mg and 2.0 mg PRN groups did not meet the prespecified noninferiority (NI) comparison. However, all treatment groups demonstrated clinically meaningful visual improvement (+8.2 to +10.1 letters) and improved anatomic outcomes, with the PRN groups requiring approximately 4 fewer injections (6.9-7.7) than the monthly groups (11.2-11.3). No new safety events were observed despite a 4-fold dose escalation in the study. The pHase III, double-masked, multicenter, randomized, Active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg Ranibizumab administered monthly or on an as-needed Basis (PRN) in patients with subfoveal neOvasculaR age-related macular degeneration (HARBOR) study confirmed that ranibizumab 0.5 mg dosed monthly provides optimum results in patients with wet AMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Macular Degeneration/drug therapy , Aged , Aged, 80 and over , Angiogenesis Inhibitors/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Intravitreal Injections , Male , Middle Aged , Ranibizumab , Tomography, Optical Coherence , Visual AcuityABSTRACT
BACKGROUND AND OBJECTIVE: To better understand the level of agreement among retina specialists on the role of inflammation in diabetic retinopathy (DR) and diabetic macular edema (DME), and the use of 0.19-mg fluocinolone acetonide (FAc) implant in DME treatment, a consensus survey was drafted and disseminated to retina specialists across the United States. MATERIALS AND METHODS: Using the modified Delphi method, a list of 12 consensus statements were generated by the coauthors based on short-answer responses to an initial survey. In total, 56 retina specialists completed the entire consensus survey. Except for two multiple-choice questions, there were 10 consensus statements that used a modified Likert scale to indicate their level of agreement to the statement: Agree = 3, Mostly Agree = 2, Mostly Disagree = 1, Disagree = 0. Percentage agreement and 95% confidence intervals (CIs) were calculated, and a consensus threshold was set at > 80% agreement for each statement. RESULTS: Seven of 10 consensus statements using the modified Likert scale reached consensus, including those on the role of inflammation in pathophysiology of DR/DME, injection burden and patient adherence, and efficacy and safety of the FAc implant. The remaining three statements displayed high agreement with average scores > 80%, but the 95% CIs were below threshold. These included the impact of the FAc implant on DR progression, FAc as baseline therapy for DME, and the effectiveness of the steroid challenge to mitigate intraocular pressure risk after FAc use. Two multiple-choice questions focused on clinical situations in which corticosteroids would be used as baseline therapy for DME (pseudophakic eye [73%], recent stroke/myocardial infarction [66%], and pregnancy/breastfeeding [66%]) and which delivery route satisfies the steroid challenge for the FAc implant (intravitreal [100%], sub-tenon/periocular [73%], and topical [57%]). CONCLUSIONS: Physicians highly agreed on the role of inflammation in pathophysiology of DR/DME, injection burden and patient adherence, and efficacy and safety of the FAc implant. However, full consensus was not found on the impact of the FAc implant on DR progression, FAc as baseline therapy for DME, and the effectiveness of the steroid challenge to mitigate intraocular pressure risk after FAc use. [Ophthalmic Surg Lasers Imaging Retina. 2023;54(3):166-173.].
Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Macular Edema , Humans , Fluocinolone Acetonide , Glucocorticoids , Diabetic Retinopathy/complications , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/drug therapy , Macular Edema/diagnosis , Macular Edema/drug therapy , Macular Edema/etiology , Drug Implants , Inflammation/drug therapy , Intravitreal Injections , Diabetes Mellitus/drug therapyABSTRACT
Purpose: This work aimed to assess the incidence of proliferative diabetic retinopathy (PDR) events and improvement to mild non-PDR (NPDR) or better after intravitreal aflibercept injection (IAI) or laser treatment (control) in diabetic macular edema (DME). Methods: PDR events in the VISTA (NCT01363440) and VIVID (NCT01331681) phase 3 clinical trials were evaluated in a combined IAI-treated group (IAI 2 mg every 4 weeks or 2 mg every 8 weeks after 5 initial monthly doses; n = 475) and a macular laser control group (n = 235) through week 100 in eyes without PDR at baseline (Diabetic Retinopathy Severity Scale [DRSS] score ≤ 53). Improvement in the DRSS score to 35 or better was evaluated in those with a baseline DRSS score of 43 or greater. Results: A lower proportion of eyes in the IAI group than in the laser group developed a PDR event through week 100 (4.4% vs 11.1%; adjusted difference, -6.7%; 97.5% CI, -11.7 to -1.6; nominal P = .0008). All PDR events occurred in eyes with a baseline DRSS score of 43, 47, or 53 and not in those with a score of 35 or less. A greater proportion of eyes in the IAI group than in the control group achieved a DRSS score of 35 or less (20.0% vs 3.8%; nominal P < .0001). Conclusions: Fewer eyes with NPDR and DME treated with IAI than eyes treated with a laser had a PDR event. More eyes treated with IAI improved to mild NPDR or better (DRSS score ≤ 35) through 100 weeks.
ABSTRACT
PURPOSE: To evaluate the safety and efficacy of a dexamethasone sustained-release intracanalicular insert (DII) (Dextenza® Ocular Therapeutix, Inc., Bedford, MA) for control of inflammation and pain after pars plana vitrectomy (PPV) compared to standard topical steroid therapy. METHODS: Retrospective, case-matched comparison of consecutive patients undergoing PPV. Control patients were matched by diagnosis and procedure performed. The primary outcome was the proportion of patients with complete anterior chamber cell clearance (ACCC) at postoperative day 7. Secondary outcomes included proportion developing intraocular pressure (IOP) >25 mmHg, change in mean optical coherence tomography central foveal thickness (OCT CFT), and proportion developing cystoid macular edema (CME) on qualitative analysis of OCT. RESULTS: The DII group had a statistically significant higher rate of complete ACCC compared to the topical steroid group (65% versus 35%, respectively, with p=0.01). No eyes had IOP >25 mmHg in the DII, compared to 2 eyes in the topical steroid group (not statistically significant). Overall, mean OCT CFT decreased in both groups; one patient had CME in the DII group, as compared to three in the topical steroid group (not statistically significant). CONCLUSION: The dexamethasone intracanalicular insert provided excellent safety and efficacy in control of postoperative inflammation following PPV in this retrospective case-matched study.
ABSTRACT
OBJECTIVE: To examine the effects of ranibizumab on the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) scores in neovascular age-related macular degeneration (AMD) according to whether the study eye was the better- or worse-seeing eye at baseline. DESIGN: Within 2 randomized, double-masked clinical trials (MARINA and ANCHOR), the NEI VFQ-25 was administered at 0, 1, 2, 3, 6, 9, 12, 18, and 24 months. PARTICIPANTS: We included 646 MARINA and 379 ANCHOR patients. INTERVENTION: Patients were randomized 1:1:1 to monthly intravitreal ranibizumab (0.3 or 0.5 mg) or control (sham injections for MARINA; photodynamic therapy [PDT] with verteporfin for ANCHOR). MAIN OUTCOME MEASURES: Mean change from baseline in NEI VFQ-25 scores at 12 and 24 months. RESULTS: Across all treatment arms, 21% to 38% of enrolled eyes were the better-seeing eye. At the 24-month follow-up visit, mean change in composite scores with ranibizumab seemed to be better than control for both better-seeing eyes (8.4 [95% confidence interval (CI), 5.2-11.6], 7.5 [95% CI, 3.7-11.4], and -9.4 [95% CI, -12.5 to -6.3] for the 0.3-mg, 0.5-mg, and sham groups, respectively) and worse-seeing eyes (1.7 [95% CI, -1.1 to 4.4], 1.7 [95% CI, -0.7 to 4.1], and -5.4 [95% CI, -7.9 to -2.8] for the 0.3-mg, 0.5-mg, and sham groups, respectively) in MARINA, as well as the better-seeing eye in ANCHOR (11.3 [95% CI, 5.3-17.3], 13.3 [95% CI, 7.7-19.0], and -2.7 [95% CI, -9.0 to 3.7] for the 0.3-mg, 0.5-mg, and PDT groups, respectively). When the worse-seeing eye was treated in ANCHOR, such differences could not be detected at 24 months (1.3 [95% CI, -1.7 to 4.2], 2.6 [95% CI, -1.1 to 6.3], and 0.1 [95% CI, -3.5 to 3.7] for the 0.3-mg, 0.5-mg, and PDT groups, respectively). CONCLUSIONS: Analysis of patient perception of vision-related function in phase III trials evaluating ranibizumab for neovascular AMD demonstrates improved patient-reported outcomes regardless of whether the treated eye is the better- or worse-seeing eye at onset of treatment, and supports treatment of such lesions with ranibizumab, even those in the worse-seeing eye. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Subject(s)
Antibodies, Monoclonal/administration & dosage , Macular Degeneration/drug therapy , Macular Degeneration/physiopathology , Photochemotherapy , Visual Acuity/physiology , Aged , Antibodies, Monoclonal, Humanized , Choroidal Neovascularization/drug therapy , Choroidal Neovascularization/physiopathology , Double-Blind Method , Female , Follow-Up Studies , Humans , Injections , Male , Photosensitizing Agents/administration & dosage , Porphyrins/administration & dosage , Ranibizumab , Sickness Impact Profile , Surveys and Questionnaires , Verteporfin , Vitreous BodyABSTRACT
PURPOSE: To describe the clinical and pathologic characteristics of a case of retinal vasculitis and vitritis following brolucizumab administration and subsequent ranibizumab treatment. OBSERVATIONS: A 76-year old Caucasian woman experienced pain, decreased vision and floaters one week after receiving her third monthly intravitreal brolucizumab injection in the right eye for exudative age-related macular degeneration. Examination was significant for 0.5+ anterior chamber cells, vitritis, mild peripheral vascular sheathing, and decreased vision from 20/70 to 20/200. She was started on topical 1% prednisolone acetate with improvement in her examination. She was switched to ranibizumab one month after her last brolucizumab injection of the right eye. Three weeks after her ranibizumab injection, she noticed photophobia, pain and decreased vision. Examination revealed worsening uveitis, vitritis, vascular sheathing, and decreased vision to count fingers. Despite starting on 0.05% difluprednate drops every 2 hours and oral high-dose methylprednisolone, the patient did not have any significant improvement in her symptoms or examination. She underwent pars plana vitrectomy and vitreous biopsy with intravitreal triamcinolone injection to the right eye. Vitreous biopsy and culture ruled out infectious endophthalmitis, and further cytopathologic analysis revealed chronic inflammatory infiltrate. CONCLUSION AND IMPORTANCE: Treatment with brolucizumab can result in intraocular inflammation and retinal vasculitis likely due to a delayed hypersensitivity reaction to the drug, supported by cytopathologic analysis of a vitreous sample. We demonstrate a case where retreatment with an alternative anti-VEGF agent resulted in worsening vision and vasculitis.
ABSTRACT
PURPOSE: Estimate effects of ranibizumab on diabetic retinopathy (DR) severity in US Hispanic and non-Hispanic white persons with center-involved diabetic macular edema (DME) causing vision impairment for whom ranibizumab treatment would be considered. PATIENTS AND METHODS: This model simulated DR severity outcomes over 2 years in the better-seeing eye using US census, National Health and Nutrition Examination Survey, Wisconsin Epidemiologic Study of Diabetic Retinopathy, and Los Angeles Latino Eye Study data. Baseline DR severity estimated from Diabetic Retinopathy Clinical Research Network trial data. Changes in DR severity after 2 years, with/without monthly ranibizumab (0.3 or 0.5 mg), were estimated from Phase III clinical trial data (RIDE/RISE) using a 2-dimensional Monte Carlo simulation model. Number of patients over a 2-year period for whom 1) DR severity worsening was avoided, 2) DR severity improved, and 3) selected clinical events related to proliferative DR (PDR) occurred, was estimated. RESULTS: An estimated 37,274 US Hispanic and non-Hispanic white persons were projected to have DR with center-involved DME and be eligible for ranibizumab treatment. The number of persons with moderately severe non-proliferative DR (NPDR) or less severe DR at baseline who would worsen to PDR and experience a PDR complication over 2 years would be reduced from 437 with no ranibizumab to 19 with ranibizumab (95% reduction; 95% simulation interval [SI], 79-100%). The number of persons with severe NPDR or less severe DR at baseline who would be expected to improve by ≥2 DR severity levels over 2 years would increase from 1706 with no ranibizumab to 13,042 with ranibizumab (682% increase; 95% SI, 478-967%). CONCLUSION: This model estimates that ranibizumab treatment in US Hispanic and non-Hispanic white patients with center-involved DME causing vision impairment would potentially reduce the number of patients with worsening DR and potentially increase the number with DR improvements.
ABSTRACT
OBJECTIVE: This study aimed to determine whether treatment with the 0.2 µg/day fluocinolone acetone implant (FAc; ILUVIEN, Alimera Sciences) and the associated improvements in best-corrected visual acuity (BCVA) and central subfield thickness (CST) demonstrated in the Fluocinolone Acetonide in Diabetic Macular Edema (FAME) study have an impact on the patient's decision to drive as measured by the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25). METHODS: This was a post hoc analysis of up to 3 years of NEI-VFQ-25 data collected during the phase III FAME trial. Patients were divided into four quartiles according to baseline NEI-VFQ-25 driving subscale (DSS) score. Patients who had never driven were excluded. Patients received either the 0.2 µg/day FAc implant or sham (dummy injection). Change in the DSS score of the NEI-VFQ-25 questionnaire over 3 years in FAc-treated versus sham-treated patients was analysed by BCVA, CST and baseline DSS score. RESULTS: The proportion of patients achieving BCVA≥20/40 was similar between the FAc and sham groups throughout the study, while improvements in CST were significantly greater in the quartile of FAc-treated patients with the lowest baseline DSS score (quartile 1; p=0.04). Significant improvements in DSS score were also observed in quartile 1 (p=0.024), while numerical-but not significant-improvements in DSS score were observed in the full cohort. CONCLUSION: This post hoc analysis demonstrates a significant association between clinical outcomes in diabetic macular oedema and improvement in quality of life measures following a single FAc implant.
ABSTRACT
INTRODUCTION: The specific impact from the patient's perspective of geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD), is not well understood. METHODS: An ethnographic study was conducted to understand the impact of bilateral GA secondary to AMD on daily functioning by observing regular activities performed at home and through semi-structured interviews. Eligible subjects had a definitive GA diagnosis, including presence of drusen, GA lesion size of at least one disc area in the better-seeing eye, and no other confounding ophthalmologic diagnosis. Data were collected via video recordings and field notes, and analyzed by coding video transcripts. RESULTS: Functional impact domains affecting more than two of the 16 subjects from the United Kingdom, United States, or Germany were activities of daily living (difficulty reading, n = 16; driving, n = 12; and watching movies, television, or theater, n = 11), emotional (frustration, and fear of blindness, n = 7 each), social/leisure (interference with hobbies, n = 8, and diminished social activities, n = 4), physical (n = 4), and financial (n = 10). Subjects with a best-corrected visual acuity (BCVA) of 20/100 or better in the better-seeing eye (n = 10) reported similar functional impacts to those with a BCVA of worse than 20/100 in their better-seeing eye (n = 5). CONCLUSION: This study helps address gaps in patient-focused research into GA, which negatively impacts the day-to-day functioning of patients. Larger qualitative and quantitative studies are needed to quantify patient experiences and assess the correlation between BCVA score and impact of GA. FUNDING: F. Hoffmann-La Roche Ltd.
ABSTRACT
PURPOSE: Oxidative injury to the retinal pigment epithelium (RPE) has been proposed to be an important injury stimulus relevant to the accumulation of subretinal deposits in age-related macular degeneration (AMD). Cigarette smoking is a major risk factor for AMD, and cigarette smoke-related tar contains high concentrations of a potent oxidant, hydroquinone (HQ). This study was an investigation of the effects of cigarette smoke (CS) and HQ in the development of sub-RPE deposits in an experimental mouse model. METHODS: Sixteen-month-old C57BL/6 female mice were fed a high-fat diet (HFD) for 4.5 months. Mice were divided into two major experimental groups, one to examine the effects of cigarette smoke and one to study the effects of a defined cigarette smoke component such as HQ. In the first group, mice eyes were exposed to blue-green light (positive controls) or to whole cigarette smoke. A third group with no intervention served as the negative control. In the second experimental group, animals received a purified diet with HQ (0.8%) with low or high fat content for 4.5 months. Mice in both groups were euthanatized at 4.5 months and eyes processed for transmission electron microscopy. RESULTS: As previously demonstrated by our laboratory and others, most mice fed an HFD without other oxidant exposure demonstrated normal morphology or, in a few cases, small nodular basal laminar deposits. Eyes of mice exposed to whole cigarette smoke or to HQ in the food demonstrated a variable degree of basal laminar deposits and diffusely thickened Bruch's membrane. The choriocapillaris endothelium was variably hypertrophic. CONCLUSIONS: Exposure to cigarette smoke or the smoke-related redox molecule, HQ, results in the formation of sub-RPE deposits, thickening of Bruch's membrane, and accumulation of deposits within Bruch's membrane. Smoke-related oxidants may be another oxidative injury stimulus to the choriocapillaris and RPE, and may explain the association between cigarette smoking and early AMD.
Subject(s)
Bruch Membrane/drug effects , Disease Models, Animal , Macular Degeneration/etiology , Oxidants/adverse effects , Pigment Epithelium of Eye/drug effects , Smoking/adverse effects , Animals , Basement Membrane/ultrastructure , Bruch Membrane/metabolism , Bruch Membrane/ultrastructure , Cotinine/blood , Dietary Fats/administration & dosage , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Extracellular Matrix/ultrastructure , Female , Hydroquinones/blood , Macular Degeneration/metabolism , Macular Degeneration/pathology , Mice , Mice, Inbred C57BL , Pigment Epithelium of Eye/metabolism , Pigment Epithelium of Eye/ultrastructure , Retina/radiation effectsABSTRACT
IMPORTANCE: The potential effect of treatments for diabetic macular edema (DME) on driving should be of value to patients and clinicians, such as ophthalmologists and other physicians, who treat patients with diabetes mellitus. OBJECTIVE: To determine the effect of ranibizumab on driving and patient-reported vision function relevant to driving among patients with DME. DESIGN, SETTING, AND PARTICIPANTS: This exploratory post hoc analysis was conducted between October 1, 2011, and July 25, 2015, based on deidentified data from phase 3, multicenter, randomized clinical trials (RIDE, RISE, and RESTORE trials). Individuals assigned randomly to monthly sham, 0.3-mg ranibizumab, or 0.5-mg ranibizumab in RIDE and RISE or to macular laser, macular laser plus 0.5-mg ranibizumab (3-monthly doses, then as needed), or 0.5-mg (3-monthly doses, then as needed) in RESTORE. MAIN OUTCOMES AND MEASURES: Driving items from the National Eye Institute (NEI) Visual Function Questionnaire-25 (VFQ-25) at baseline through 24 months in RIDE/RISE (pooled) and through 12 months in RESTORE. RESULTS: A total of 71.2% of 753 patients in RIDE/RISE and 50.4% of 345 patients in RESTORE reported driving at baseline; at least 55% reported still driving at follow-up. Among those not driving at baseline in RIDE/RISE, at 12 months, 7.0% (95% CI, -5.0 to 19.0) more in the 0.3-mg group and 14.4% (95% CI, 1.1 to 27.7) more in the 0.5-mg group vs the sham group reported driving. Among those not driving at baseline in RESTORE, at 12 months, 4.2% (95% CI, -7.7 to 16.1) more in the laser plus 0.5-mg group and 0.9% (95% CI, -10.3 to 12.1) more in the 0.5-mg group vs the laser group reported driving. Although balanced at baseline across treatment groups for RESTORE and RIDE/RISE, the proportion of patients with best-corrected visual acuity typically required for an unrestricted license (20/40 or better in at least 1 eye) appeared greater at month 12 in the ranibizumab groups (77 of 80 [96.3%] for 0.5 mg + laser and 91 of 93 [97.8%] for 0.5 mg) vs laser (71 of 79 [89.9%]) in RESTORE, and at months 12 (112 of 123 [91.1%] and 136 of 137 [99.3%] in 0.3- and 0.5-mg groups, respectively) and 24 (113 of 123 [91.9%] and 135 of 137 [98.5%] in the 0.3- and 0.5-mg groups, respectively) vs sham (121 of 147 [82.3%] and 122 of 147 [83.0%]) in RIDE/RISE. CONCLUSIONS AND RELEVANCE: These results suggest that 12 months after initiating ranibizumab for vision impairment from center-involved DME, patients not driving at initiation of treatment are more likely to report driving and have driving-eligible visual acuity of 20/40 or better in the better-seeing eye than those treated with sham or laser. TRIAL REGISTRATION: clinicaltrials.gov Identifier: RESTORE: NCT00687804; RIDE: NCT00473382; and RISE: NCT00473330.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Automobile Driving/statistics & numerical data , Diabetic Retinopathy/drug therapy , Macular Edema/drug therapy , Ranibizumab/therapeutic use , Visual Acuity/physiology , Adult , Aged , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/physiopathology , Double-Blind Method , Female , Humans , Intravitreal Injections , Macular Edema/diagnosis , Macular Edema/physiopathology , Male , Middle Aged , Quality of Life , Sickness Impact Profile , Surveys and Questionnaires , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visually Impaired Persons/rehabilitationABSTRACT
PURPOSE: Macrophage recruitment to the choroid has been proposed to contribute to the pathogenesis of choroidal neovascularization (CNV) in AMD. The study was conducted to determine whether treatment with clodronate liposomes (CL(2)MDP-lip), which cause depletion of blood monocytes and lymph node macrophages, diminishes the severity of neovascularization in a mouse model of laser-induced CNV. METHODS: Laser-induced CNV was performed in female 16-month-old C57BL/6 mice. Macrophages were depleted by use of CL(2)MDP-lip intraperitoneally and subcutaneously 72 and 24 hours before and every 2 to 3 days after laser injury. Control mice received injections of either PBS alone or PBS liposomes. Blood monocyte and choroidal macrophage depletion were documented by flow cytometry and choroidal flatmount preparation analysis, respectively. Two weeks after laser injury, mice were injected intravenously with fluoresceinated dextran. The right eyes were removed and prepared for flatmount analysis of CNV surface area (in relative disc areas or DA), vascularity (relative fluorescence), and cellularity (propidium iodide stain). The mice were then perfused with 10% formaldehyde, and the left eyes were removed for histopathology. The means of the various parameters for four CNV lesions per eye were calculated. Fluorescein angiography was also performed. RESULTS: Flow cytometry of circulating monocytes and immunohistochemical analysis of choroidal macrophage density confirmed the effective depletion of blood monocytes and choroidal macrophages respectively in CL(2)MDP-lip-treated mice. Compared with the control, flatmount analysis of macrophage depleted mice demonstrated a significant reduction in size of the CNV area (2.8 +/- 0.5 DA vs. 1.4 +/- 0.1 DA; P < 0.043). The treated group also revealed less vascularity (1.6 +/- 0.1 units vs. 1.1 +/- 0.0 units; P < 0.0092) and cellularity of CNV lesions (3.3 +/- 0.6 DA vs. 1.7 +/- 0.1 DA, P < 0.04). Histopathology revealed that, in the macrophage-depleted group, CNV was smaller in diameter (1270 +/- 73 pixels vs. 770 +/- 82 pixels, P < 0.0006) and thickness (120 +/- 7 pixels vs. 96 +/- 7 pixels, P < 0.019). CONCLUSIONS: Macrophage depletion using CL(2)MDP-lip reduces size, cellularity, and vascularity of CNV. This observation supports the hypothesis that macrophages contribute to the severity of CNV lesions.
Subject(s)
Choroidal Neovascularization/metabolism , Choroidal Neovascularization/pathology , Macrophages/physiology , Animals , Antimetabolites/administration & dosage , Cell Count , Choroid/blood supply , Choroidal Neovascularization/prevention & control , Clodronic Acid/administration & dosage , Dextrans , Disease Models, Animal , Female , Flow Cytometry , Fluoresceins , Liposomes , Macrophages/drug effects , Mice , Mice, Inbred C57BLABSTRACT
PURPOSE: Cigarette smoking is the strongest environmental risk factor for all forms of age-related macular degeneration (AMD). In the present study, the influence of nicotine on the severity of choroidal neovascularization (CNV) in a mouse model of neovascular AMD and its effects on vascular smooth muscle cells derived from mouse choroid were investigated. METHODS: A mouse model for CNV was used to study the effects of nicotine in young and middle-aged mice. Nicotine was administered orally in the drinking water to achieve serum levels consistent with those of chronic smokers. Hexamethonium, a nonspecific nicotinic receptor antagonist, was injected subconjunctivally to counteract the effects of nicotine. A mouse choroidal vascular smooth muscle cell line was exposed to nicotine, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), or a combination of one of the factors and nicotine. Cell growth was determined by cell counts, and the activity of matrix metalloproteinase (MMP)-2 and -9 was quantified by gel zymography. RESULTS: Nicotine administration resulted in increased size and vascularity of CNV, and older mice developed a greater relative increase than younger mice. This effect was blocked by subconjunctival hexamethonium. Choroidal vascular smooth muscle cells demonstrated a statistically significant increase in growth after exposure to a combination of PDGF and nicotine. Nicotine also reversed VEGF-induced suppression of MMP-2 activity. CONCLUSIONS: Nicotine increases size and severity of experimental CNV in the present mouse model, possibly by potentiating PDGF-mediated upregulation of proliferation of choroidal smooth muscle cells or by other mechanisms. These results suggest that non-neuronal nicotinic receptor activation probably mediates some of the harmful effects of cigarette smoking in wet AMD.