Purpose: To determine efficacy and safety of intravitreal aflibercept in patients with neovascular age-related macular degeneration (AMD) during a second year of variable dosing after a first-year fixed-dosing period.Design: Two randomized, double-masked, active-controlled, phase 3 trials.Participants: Two thousand four hundred fifty-seven patients with neovascular AMD.Methods: From baseline to week 52, patients received 0.5 mg intravitreal ranibizumab every 4 weeks (Rq4), 2 mg aflibercept every 4 weeks (2q4), 0.5 mg aflibercept every 4 weeks (0.5q4), or 2 mg aflibercept every 8 weeks (2q8) after 3 monthly injections. During weeks 52 through 96, patients received their original dosing assignment using an as-needed regimen with defined retreatment criteria and mandatory dosing at least every 12 weeks.Main Outcome Measures: Proportion of eyes at week 96 that maintained best-corrected visual acuity (BCVA; lost <15 letters from baseline); change from baseline in BCVA.Results: Proportions of eyes maintaining BCVA across treatments were 94.4% to 96.1% at week 52 and 91.5% to 92.4% at week 96. Mean BCVA gains were 8.3 to 9.3 letters at week 52 and 6.6 to 7.9 letters at week 96. Proportions of eyes without retinal fluid decreased from week 52 (60.3% to 72.4%) to week 96 (44.6% to 54.4%), and more 2q4 eyes were without fluid at weeks 52 and 96 than Rq4 eyes (difference of 10.4% [95% confidence interval {CI}, 4.9–15.9] and 9.0% [95% CI, 3.0–15.1]). Patients received on average 16.5, 16.0, 16.2, and 11.2 injections over 96 weeks and 4.7, 4.1, 4.6, and 4.2 injections during weeks 52 through 96 in the Rq4, 2q4, 0.5q4, and 2q8 groups, respectively. The number of injections during weeks 52 through 96 was lower in the 2q4 and 2q8 groups versus the Rq4 group (differences of −0.64 [95% CI, −0.89 to −0.40] and −0.55 [95% CI, −0.79 to −0.30]; P < 0.0001, post hoc analysis). Incidences of Antiplatelet Trialists’ Collaboration–defined arterial thromboembolic events were similar across group (2.4% to 3.8%) from baseline to week 96.Conclusions: All aflibercept and ranibizumab group were equally effective in improving BCVA and preventing BCVA loss at 96 weeks. The 2q8 aflibercept group was similar to ranibizumab in visual acuity outcomes during 96 weeks, but with an average of 5 fewer injections. Small losses at 96 weeks in the visual and anatomic gains seen at 52 weeks in all arms were in the range of losses commonly observed with variable dosing.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.
Category: Peer-reviewed
Mutations in the Mevalonate Kinase (MVK) Gene Cause Nonsyndromic Retinitis Pigmentosa – Corrected Proof
Objective: Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous disorder characterized by night blindness and peripheral vision loss, and in many cases leads to blindness. Despite extensive knowledge about genes involved in the patho…
High Prevalence of Peripheral Retinal Vascular Anomalies in Family Members of Patients with Familial Exudative Vitreoretinopathy – Corrected Proof
Objective: To describe the prevalence and severity of familial exudative vitreoretinopathy (FEVR) in asymptomatic relatives of known symptomatic FEVR patients.Design: Uncontrolled and retrospective case series at a single tertiary referral vitreoretina…
Intravitreal Aflibercept Injection for Macular Edema Resulting from Central Retinal Vein Occlusion: One-Year Results of the Phase 3 GALILEO Study – Corrected Proof
Purpose: To evaluate the efficacy and safety of intravitreal aflibercept injections for treatment of macular edema secondary to central retinal vein occlusion (CRVO).Design: A randomized, multicenter, double-masked phase 3 study.Participants: A total of 177 treatment-naive patients with macular edema secondary to CRVO were randomized in a 3:2 ratio.Methods: Patients received either 2-mg intravitreal aflibercept or sham injections every 4 weeks for 20 weeks. From week 24 to 48, the aflibercept group received aflibercept as needed (pro re nata [PRN]), and the sham group continued receiving sham injections.Main Outcome Measures: The primary efficacy end point was the proportion of patients who gained 15 letters or more in best-corrected visual acuity (BCVA) at week 24. This study reports week 52 results including the proportion of patients who gained 15 letters or more in BCVA and the mean change from baseline BCVA and central retinal thickness. Efficacy end points at week 52 were all exploratory.Results: At week 52, the mean percentage of patients gaining 15 letters or more was 60.2% in the aflibercept group and 32.4% in the sham group (P = 0.0004). Aflibercept patients, compared with sham patients, had a significantly higher mean improvement in BCVA (+16.9 letters vs. +3.8 letters, respectively) and reduction in central retinal thickness (−423.5 μm vs. −219.3 μm, respectively) at week 52 (P < 0.0001 for both). Aflibercept patients received a mean of 2.5 injections (standard deviation, 1.7 injections) during PRN dosing. The most common ocular adverse events in the aflibercept group were related to the injection procedure or the underlying disease, and included macular edema (33.7%), increased intraocular pressure (17.3%), and eye pain (14.4%).Conclusions: Treatment with intravitreal aflibercept provided significant functional and anatomic benefits after 52 weeks as compared with sham. The improvements achieved after 6 monthly doses at week 24 largely were maintained until week 52 with as-needed dosing. Intravitreal aflibercept generally was well tolerated.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.
Anterior Capsulotomy Integrity after Femtosecond Laser-Assisted Cataract Surgery – Corrected Proof
Objective: To compare the incidence of anterior capsular tears after femtosecond laser-assisted cataract surgery (FLACS) versus phacoemulsification cataract surgery (PCS) and to assess the ultrastructural features of anterior capsulotomy specimens (FLA…
Cost-Effectiveness of Osteo-Odonto Keratoprosthesis in Singapore – Corrected Proof
Purpose: To determine the long-term cost-effectiveness of osteo-odonto keratoprosthesis (OOKP) relative to no treatment among patients with end-stage corneal and ocular surface diseases in Singapore.Design: Cost-effectiveness analysis based on data fro…
The Association between Cataract Surgery and Atypical Antipsychotic Use: A Nested Case-Control Study – Corrected Proof
Purpose: To investigate cataract risk associated with the use of atypical antipsychotics.Design: Retrospective, nested case-control study.Methods: A large health claims database (The British Columbia Ministry of Health Databases) from British Columbia,…
Macular Ganglion Cell/Inner Plexiform Layer Measurements by Spectral Domain Optical Coherence Tomography for Detection of Early Glaucoma and Comparison to Retinal Nerve Fiber Layer Measurements – Corrected Proof
Purpose: To evaluate the performance of ganglion cell layer/inner plexiform layer (GCL/IPL) measurements with spectral-domain optical coherence tomography (Cirrus HD-OCT) for detection of early glaucoma and to compare results to retinal nerve fiber layer (RNFL) measurements.Design: Cross-sectional prospective diagnostic study.Methods: We enrolled 99 subjects, including 59 eyes with glaucoma (47 subjects) (mean deviation >−6.0 dB) and 91 normal eyes (52 subjects). Patients underwent biometry and peripapillary and macular OCT imaging. Performance of the GCL/IPL and RNFL algorithms was evaluated with area under receiver operating characteristic curves (AUC), likelihood ratios, and sensitivities/specificities adjusting for covariates. Combination of best parameters was explored.Results: Average (SD) mean deviation in the glaucoma group was −2.5 (1.9) dB. On multivariate analyses, age (P < 0.001) and axial length (P = 0.03) predicted GC/IPL measurements in normal subjects. No significant correlation was found between average or regional GC/IPL thickness and respective outer retina (OR) thickness measurements (P > 0.05). Average RNFL thickness performed better than average GCL/IPL measurements for detection of glaucoma (AUC = 0.964 vs 0.937; P = 0.04). The best regional measures from each algorithm (inferior quadrant RNFL vs minimum GCL/IPL) had comparable performances (P = 0.78). Entering the GC/IPL to OR ratio into prediction models did not enhance the performance of the GCL/IPL measures. Combining the best parameters from each algorithm improved detection of glaucoma (P = 0.04).Conclusions: Regional GCL/IPL measures derived from Cirrus HD-OCT performed as well as regional RNFL outcomes for detection of early glaucoma. Using the GC/IPL to OR ratio did not enhance the performance of GCL/IPL parameters. Combining the best measures from the 2 algorithms improved detection of glaucoma.
The Effect of Enoxaparin-Containing Irrigation Fluid Used During Cataract Surgery on Postoperative Inflammation in Patients With Diabetes – Corrected Proof
Purpose: To investigate effects of enoxaparin on postoperative inflammation in patients with moderate nonproliferative diabetic retinopathy (NPDR) and nuclear cataract.Design: Prospective masked controlled trial.Methods: setting: Institutional practice. study population: The study included 51 eyes of 51 diabetes mellitus (DM) patients with moderate NPDR and grade 2-3 nuclear cataracts. Group 1 included randomly selected patients who received enoxaparin in balanced salt solution (BSS) during cataract surgery, while standard BSS was used in Group 2. observation procedure: Patients were followed up 1 day, 1 week, and 1 and 2 months after the surgery. main outcome measures: Anterior chamber cell and flare.Results: Postoperatively, 20 patients from Group 1 and 4 patients in Group 2 had less than a mean of 10 cells at day 1 (P = .012). At the first week, 20 patients from Group 1 and 10 patients from Group 2 had less than a mean of 10 cells (P = .004). When compared for flare, 20 patients from Group 1 and 8 patients from Group 2 had a flare between 0 and +1 at postoperative day 1 (P < .001). By the end of postoperative first week, 24 patients from Group 1and 18 patients from Group 2 had a flare between 0 and +1 (P = .012). There was no difference between groups in terms of postoperative inflammation at the first and second months after the surgery.Conclusion: The results of the study suggest that enoxaparin added into the infusion fluid may reduce postoperative inflammation in patients with DM, and this result supports the anti-inflammatory effect of enoxaparin.
Retinal Asymmetry in Children Measured With Optical Coherence Tomography – Corrected Proof
Purpose: To determinate the physiological asymmetry of retinal measurements in the pediatric population with Fourier-domain optical coherence tomography (Cirrus HD-OCT).Design: Prospective cross-sectional study.Methods: Three hundred and fifty-seven he…
Expanding the Cone Location and Magnitude Index to Include Corneal Thickness and Posterior Surface Information for the Detection of Keratoconus – Corrected Proof
Purpose: To extend the capabilities of the Cone Location and Magnitude Index algorithm to include a combination of topographic information from the anterior and posterior corneal surfaces and corneal thickness measurements to further improve our abilit…
Evaluating the Accuracy of the Visual Field Index for the Humphrey Visual Field Analyzer in Patients with Mild to Moderate Glaucoma – Corrected Proof
Purpose: To evaluate the accuracy of the visual field index (VFI) for the Humphrey Visual Field Analyzer in a population of patients with mild to moderate glaucoma.Design: Retrospective cohort study.Methods: The study included 42 patients (61 eyes) with at least 11 years of follow-up, and annual automated visual fields (VFs). Patients with mean deviations ≤−20 dB were excluded. All unreliable fields were omitted (fixation losses ≥20%, false-positive ≥15%, false-negative ≥33%). The VFs were divided into two 5-year series and the data were analyzed by the new Humphrey Visual Field Analyzer software. Projected VFIs from the first 5 years were compared with observed values obtained from the last 5 years. Unreliable fields initially excluded were reintroduced into the series (22 eyes) to create a comparison.Results: Predicted VFIs were accurate with a mean overestimation of VF deterioration of 1.37% (95% CI: −0.22%, 2.96%). Of the predicted values, 95% were between −4.5% and 5.2% of the observed values when the predicted VFI was ≥90%; and between −13.8% and 20.5% when the predicted VFI was <90%. No statistical difference was found between the reliable and unreliable series (mean difference of 0.09% [95% CI: −0.41%, 0.59%]).Conclusion: The new software for the Humphrey Visual Field Analyzer projects an accurate value for patients when the predicted VFI is ≥90%. Clinicians should consider the limitations of the software, especially for those patients with greater initial VF loss.
Reticular Pattern Dystrophy of the Retina: A Spectral-Domain Optical Coherence Tomography Analysis – Corrected Proof
Purpose: To analyze the outer retinal and retinal pigment epithelium (RPE) features of reticular pattern dystrophy of the retina using spectral-domain optical coherence tomography (SDOCT).Design: Retrospective observational case series.Methods: Consecu…
Prognostic Factors of Eyes With Naïve Subfoveal Myopic Choroidal Neovascularization After Intravitreal Bevacizumab – Corrected Proof
Purpose: To determine the efficacy of 1 intravitreal bevacizumab injection followed by pro re nata (1 + PRN) injection in cases of subfoveal myopic choroidal neovascularization (CNV) and to identify CNV-recurrence–related prognostic factors.Design: Retrospective observational case series.Methods: In total, 103 eyes of 89 consecutive naive patients who had subfoveal myopic CNV and had been followed-up for at least 2 years were included. Of those eyes, 24 had recurrences. The remaining eyes were stable after the initial treatment.Results: The average patient age was 51.1 ± 15.2 years. The average follow-up duration was 44.1 ± 12.7 months. At baseline and at the 1-year, 2-year, and final visits, the average best corrected visual acuities (BCVAs) were 0.57 ± 0.45, 0.38 ± 0.51, 0.40 ± 0.52, and 0.41 ± 0.41 logMAR, respectively. The recurrence rate during follow-up was 23.3%. The BCVA improved by 0.2 logMAR after 2.7 injections in the eyes without recurrence but by only 0.08 logMAR after 6.9 injections in the eyes with recurrence. In univariate analysis, recurrence was associated with older age, more myopic refraction, thinner choroid, larger CNV lesions, and subfoveal hemorrhage at baseline. In multivariate analysis, only baseline CNV lesion size associated significantly with CNV recurrence (P = 0.002). Recurrence, baseline BCVA, choroidal thickness, and CNV size associated significantly with final BCVA (P = 0.026, <0.0001, 0.007, and 0.002, respectively). Baseline choroidal thickness, CNV size, age, and presence of lacquer cracks associated significantly with injection number (P < 0.0001, <0.0001, 0.026, and 0.035, respectively).Conclusions: 1 + PRN intravitreal bevacizumab monotherapy effectively stabilized subfoveal myopic CNV. The CNV size, the baseline BCVA, and the choroidal thickness were the main prognostic factors of subfoveal myopic CNV after 1 + PRN injection of bevacizumab.
Detection and Influencing Factors of Capsular Bag Distention Syndrome after Cataract Surgery Using the Pentacam Scheimpflug System – Corrected Proof
Purpose: To investigate the prevalence and morphologic changes of capsular bag distention syndrome after cataract surgery using the Pentacam and to analyze its clinical characteristics and influencing factors.Design: Retrospective, cross-sectional study.Methods: Clinical records of 239 consecutive patients who underwent cataract surgery were reviewed. Demographic data, use of intraoperative ophthalmic viscosurgical devices, type of intraocular lens implanted, axial length, and white-to-white corneal diameter were recorded. One month after surgery, dilated Scheimpflug imaging was performed. Prevalence, morphologic changes, and characteristic clinical findings of this syndrome were evaluated.Results: Using Scheimpflug imaging, the prevalence of capsular bag distention syndrome was high at 26.8% (64/239), and it was possible to classify its morphologic changes into 3 types. Patients with the syndrome had poorer best-corrected visual acuity and lower satisfaction scores than those without the syndrome (P = .041 and P = .008, respectively). Although there was no significant difference observed in rate of this syndrome between the 2 ophthalmic viscosurgical devices used in our study (P > .05), implantation of 4-haptic intraocular lenses was associated with a high prevalence of the syndrome (odds ratio, 2.07; 95% confidence interval, 1.05 to 4.07; P = .0346). Patients with this syndrome had significantly longer AL (26.26 ± 2.84 mm) and white-to-white diameter (12.02 ± 0.34 mm) than those without (AL, 24.63 ± 2.89 mm; white-to-white diameter, 11.81 ± 0.32 mm; P = .0002 and P < .0001, respectively).Conclusions: Scheimpflug imaging revealed the prevalence of capsular bag distention syndrome to be high, and these patients generally had poorer visual outcomes. Intraocular lens design and dimensions of the eyes significantly influenced the prevalence of this syndrome.
Treatment of Persistent Corneal Epithelial Defect With Overnight Wear of a Prosthetic Device for the Ocular Surface – Corrected Proof
Purpose: To report experience in the treatment of persistent corneal epithelial defect using overnight wear of a prosthetic device for the ocular surface.Design: Retrospective interventional case series.Methods: A clinical database of patients who underwent prosthetic replacement of the ocular surface ecosystem (PROSE) treatment from March 2003 to August 2008 was searched to identify patients treated for persistent corneal epithelial defect. In early 2003, overnight wear of a PROSE device and addition of commercially available, nonpreserved, topical ophthalmic moxifloxacin to the saline in the device reservoir became standard practice at this center when treating persistent corneal epithelial defect. Medical records were abstracted to obtain underlying diagnoses, previous treatments, days to re-epithelialization, and complications for subsequent analysis.Results: PROSE treatment incorporating overnight wear, with adjunctive use of moxifloxacin, was employed in 20 eyes of 19 patients for a total of 372 days. Re-epithelialization occurred in 17 of 20 eyes. Median duration of treatment incorporating overnight wear was 8.5 days (range = 2-76 days). Healing occurred in ≤7 days in 12 eyes, 8-14 days in 3 eyes, and >14 days in 2 eyes (range = 1-35 days). There were no cases of microbial keratitis.Conclusions: Overnight wear of a PROSE device is effective in promoting healing of persistent corneal epithelial defect. In comparison to an earlier series from this center, the rate of microbial keratitis as a complication of treatment has been reduced with the use of a nonpreserved topical fourth-generation fluoroquinolone in the device reservoir.
Demographic Patterns and Treatment Outcomes of Patients With Recurrent Corneal Erosions Related to Trauma and Epithelial and Bowman Layer Disorders – Corrected Proof
Purpose: To evaluate demographics and outcomes of patients with recurrent corneal erosions related to trauma and epithelial and Bowman layer disorders.Design: Retrospective case series.Methods: setting: Wills Eye Institute, Philadelphia, Pennsylvania. study population: Two hundred seventy-two eyes (230 patients) presenting between 2008 and 2011 with recurrent corneal erosions related to trauma and epithelial and Bowman layer disorders. procedure: Conservative management, diamond burr polishing, excimer laser phototherapeutic keratectomy (PTK), and epithelial debridement alone. main outcome measure: Recurrence of erosions, more than 6 weeks after commencing treatment.Results: Mean age was 46.5 ± 14.6 (2-85) years. Female subjects accounted for 53% of patients and 18.3% had bilateral involvement. Etiology included epithelial basement membrane dystrophy in 52.9% (144/272) and trauma in 25.7% (70/272). One hundred sixty-six eyes with more than a single visit were initially managed conservatively, 68 of 166 (40.9%) had diamond burr polishing, 7 of 166 (4.2%) had PTK, and 4 of 166 (2.4%) had epithelial debridement alone. Many eyes had >6 weeks follow-up: 120 of 166 (72.3%) after conservative management, 54 of 68 (79.4%) after diamond burr polishing, 7 of 7 (100%) after PTK, and 4 of 4 (100%) after epithelial debridement. Percentage of eyes with recurrence was 56.7% (68/120) after conservative management, 14.8% (8/54) after diamond burr polishing, and 28.6% (2/7) after PTK. Rate of recurrence (eye-years) was 0.74, 0.19, and 0.23 with conservative management, diamond burr polishing, and PTK, respectively. Mild haze was seen in 22.2% of eyes (12 eyes) after diamond burr polishing and 28.6% (2 eyes) after PTK.Conclusion: Recurrent corneal erosions are most commonly associated with epithelial basement membrane dystrophy. Patients are generally initially managed conservatively, with recurrence in more than half of eyes. Diamond burr polishing is the most common surgical intervention and is effective in a majority of eyes.
Optical Coherence Tomography–Guided Transepithelial Phototherapeutic Keratectomy for the Treatment of Anterior Corneal Scarring – Corrected Proof
Purpose: To report the visual and anatomic outcomes of a novel technique for the management of anterior corneal scarring using optical coherence tomography (OCT)–guided transepithelial phototherapeutic keratectomy (transepithelial PTK).Design: Retros…
Six-Year Incidence of Angle-Closure Disease in a South Indian Population: The Chennai Eye Disease Incidence Study – Corrected Proof
Purpose: To estimate the 6-year incidence of primary angle-closure (PAC) disease among adult population aged 40 years and older from rural and urban south India.Design: Population-based longitudinal study.Methods: A complete ophthalmologic examination,…
Effectiveness of Nonpharmacologic Treatments for Acute Seasonal Allergic Conjunctivitis – Corrected Proof
Objective: To investigate whether artificial tears and cold compress alone or in combination provide a treatment benefit and whether they were as effective as or could enhance topical antiallergic medication.Design: Randomized, masked clinical trial.Participants: Eighteen subjects (mean age, 29.5±11.0 years) allergic to grass pollen.Intervention: Controlled exposure to grass pollen using an environmental chamber to stimulate an ocular allergic reaction followed by application of artificial tears (ATs), 5 minutes of cold compress (CC), ATs combined with CC, or no treatment applied at each separate visit in random order. A subset of 11 subjects also had epinastine hydrochloride (EH) applied alone and combined with CC in random order or instillation of a volume-matched saline control.Main Outcome Measures: Bulbar conjunctival hyperemia, ocular surface temperature, and ocular symptoms repeated before and every 10 minutes after treatment for 1 hour.Results: Bulbar conjunctival hyperemia and ocular symptoms decreased and temperature recovered to baseline faster with nonpharmaceutical treatments compared with no treatment (P 0.05). At all measurement intervals, symptoms were reduced for both EH and EH combined with CC than CC or ATs alone or in combination (P < 0.014).Conclusions: After controlled exposure to grass pollen, CC and AT treatment showed a therapeutic effect on the signs and symptoms of allergic conjunctivitis. A CC enhanced the use of EH alone and was the only treatment to reduce symptoms to baseline within 1 hour of antigenic challenge. Signs of allergic conjunctivitis generally were reduced most by a combination of a CC in combination with ATs or EH.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.