Diabetic Retinopathy Study Visual Acuity Research Articles

A 12-MONTH, SINGLE-MASKED, RANDOMIZED CONTROLLED STUDY OF EYES WITH PERSISTENT DIABETIC MACULAR EDEMA AFTER MULTIPLE ANTI-VEGF INJECTIONS TO ASSESS THE EFFICACY OF THE DEXAMETHASONE-DELAYED DELIVERY SYSTEM AS AN ADJUNCT TO BEVACIZUMAB COMPARED WITH CONTINUED BEVACIZUMAB MONOTHERAPY.

To determine whether a dexamethasone intravitreal implant 0.7 mg (dexamethasone delivery system [DDS], Ozurdex) combined with bevacizumab 1.25 mg (Avastin) provides greater benefit than bevacizumab monotherapy in eyes with diabetic macular edema with incomplete response to multiple antivascular endothelial growth factor injections. Eyes with diabetic macular edema were randomly assigned to receive combination therapy (bevacizumab plus DDS) or bevacizumab monotherapy. Combination therapy eyes received intravitreal bevacizumab at baseline, DDS at Month 1, and subsequent DDS (at Months 5 and 9), whereas monotherapy eyes received bevacizumab (monthly) if indicated. Eyes were eligible for retreatment if the central subfield thickness measured >250 μm, and Early Treatment of Diabetic Retinopathy Study visual acuity was <80 letters (20/25). Forty eyes of 30 patients were enrolled. The mean visual acuity changes from baseline to 12 months were similar in the 2 groups (combined: +5.4 letters; bevacizumab: +4.9 letters; difference = 0.2 letters, 95% confidence interval = -5.9 to 6.3; P = 0.75). The mean reduction in central subfield thickness was greater in the combination group (-45 μm vs. -30 μm, difference = 69 μm, 95% confidence interval = 9-129; P = 0.03) and more patients in the combination group had central subfield thickness <250 μm. The combined treatment group received three fewer supplemental injections of bevacizumab, but this was counterbalanced by the need for an average of 2.1 DDS injections. The dexamethasone implant combined with bevacizumab significantly improves visual acuity and significantly improves macular morphology in eyes with refractory diabetic macular edema, although visual acuity changes are not superior to continued bevacizumab monotherapy.

Long-term outcomes of intravitreal ranibizumab for neovascular age-related macular degeneration in a well defined region of the UK

AimsTo study long-term, whole population ‘real-world’ clinical outcomes of ranibizumab therapy in treatment-naïve eyes for neovascular age-related macular degeneration.MethodsData collected prospectively from a single centre serving a defined population using...

Visual Acuity, Contrast Sensitivity and Color Vision Three Years After Iodine-125 Brachytherapy for Choroidal and Ciliary Body Melanoma.

Purpose : To report visual acuity, contrast sensitivity and color vision prior to, 1 year after, 2 years after and 3 years after iodine-125 brachytherapy for choroidal and ciliary body melanoma (CCM).Design : Prospective interventional case series.Participants : Thirty-seven patients (37 eyes) with CCM.Methods : Patients had best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, Pelli-Robson contrast sensitivity and Hardy-Rand-Rittler color vision measurement; comprehensive ophthalmology examination; optical coherence tomography; and ultrasonography at baseline prior to, 1 year after, 2 years after and 3 years after I-125 brachytherapy.Main Outcome Measures : Visual acuity, contrast sensitivity and color vision prior to, 1 year after, 2 years after and 3 years after brachytherapy.Results :Nineteen (19) men and 18 women with mean age of 58 years (SD 13, range 30-78) prior to, 1 year after, 2 years after and 3 years after brachytherapy had mean best-corrected visual acuity of 77 letters (20/32), 65 letters (20/50), 56 letters (20/80) and 47 letters (20/125); contrast sensitivity of 30, 26, 22 and 19 letters; color vision of 26, 20, 17 and 14 test figures, respectively. Decrease in visual acuity, contrast sensitivity and color vision was statistically significant from baseline at 1 year, 2 years, and 3 years after brachytherapy. Decreased acuity at 3 years was associated with mid-choroid and macula melanoma location, ≥ 4.1 mm melanoma height, radiation maculopathy and radiation optic neuropathy.Conclusion : 1, 2 and 3 years after brachytherapy, eyes with CCM had significantly decreased visual acuity, contrast sensitivity and color vision.

Macular Atrophy Progression and 7-Year Vision Outcomes in Subjects From the ANCHOR, MARINA, and HORIZON Studies: the SEVEN-UP Study

To assess the incidence and progression of macular atrophy and other key anatomic outcomes over 7 to 8 years in an early cohort of ranibizumab-treated exudative age-related macular degeneration patients. Follow-up analysis of long-term outcomes in a multicenter treatment cohort. Fourteen study sites enrolled 65 previous subjects from the ranibizumab treatment arms of the ANCHOR, MARINA, and HORIZON trials. In a single update visit, clinical assessment and retinal imaging studies were performed, with comparison with each subject's prior results from the previous trials. Early Treatment Diabetic Retinopathy Study visual acuity was the primary outcome. Secondary outcomes, including area of macular atrophy and selected anatomic factors, were analyzed for associations with long-term vision outcomes. At a mean 7.3 years after ANCHOR or MARINA enrollment, mean visual acuity was 54 letters, study eyes having received a mean 1.6 injections per year since the HORIZON study. Macular atrophy was present in 98% of study eyes, the mean area increasing from 0.83± 0.96mm(2) at the ANCHOR or MARINA year 2 exit to 2.22 ± 1.6mm(2) at the SEVEN-UP visit, a growth rate of 0.28mm(2)/year. Progression of macular atrophy was associated significantly with visual decline over this 5-year period (P < .001), and final macular atrophy lesion size was related significantly to final vision (P < .001). Other key anatomic outcomes (macular thickening, thinning, or fluid and submacular fibrosis) did not have significant effects on vision outcomes. Seven years after initiation of intensive ranibizumab therapy for exudative age-related macular degeneration, macular atrophy progression and severity were the primary anatomic determinants of visual outcomes.

Occurrence of macular hematoma after ranibizumab treatment for age-related macular degeneration.

To report the occurrence and study the characteristics of macular hematoma after ranibizumab (anti-VEGF) intravitreal injection for subfoveal choroidal neovascularization in age-related macular degeneration (AMD). The charts of 6000 patients treated with ranibizumab (0.5 mg) for exudative AMD were reviewed. Inclusion criteria were a minimum follow-up of 1 year after the first injection and the occurrence of a large macular hematoma involving the fovea in patients with macular lesions considered stabilized or still active. All patients had a complete ophthalmologic assessment including Early Treatment of Diabetic Retinopathy Study visual acuity (VA) measurement, fundus photography, fundus fluorescein angiography, scanning laser ophthalmoscopy-infracyanine green angiography, and spectral-domain optical coherence tomography. Of the 6000 eyes, 24 (0.4%) developed macular hematoma during follow-up. There were 8 men (33.3%) and 16 women (66.7%). The mean age at the time of initial presentation was 76.7 ± 3.8 years (range 61-81 years). The mean time to occurrence of macular hematoma after the last injection was 4.8 months. Spectral-domain optical coherence tomography showed the presence of a retinal pigment epithelium (RPE) tear in 19 eyes (79.1%). Vitreomacular traction (VMT) was only present in 4 eyes (17%). Final VA after macular hematoma resorption was &lt;20/50 in 17 cases (70.9%) and ≥20/50 in 7 cases (29.1%). Macular hematoma may follow intravitreal anti-VEGF injection for exudative AMD with large occult neovascularization, especially if a large RPE tear is found. The occurrence does not seem to be linked to anticoagulation treatment or the presence of VMT.

Short-term safety and efficacy of intravitreal 0.7-mg dexamethasone implants for pseudophakic cystoid macular edema

AimsTo determine the feasibility, safety, and clinical efficacy of intravitreal 0.7-mg dexamethasone implants (Ozurdex) in patients with refractory cystoid macular edema after uncomplicated cataract surgery. Methods and materialsIn this study, 11 eyes of 11 patients affected by pseudophakic cystoid macular edema refractory to medical treatment were treated with a single intravitreal injection of a dexamethasone implant. Follow-up visits involved Early Treatment Diabetic Retinopathy Study visual acuity testing, optical coherence tomography imaging, and ophthalmoscopic examination. ResultsThe follow-up period was six months. The mean duration of cystoid macular edema before treatment with Ozurdex was 7.7months (range, 6–10months). The baseline mean best corrected visual acuity (BCVA) was 0.58±0.17 logarithm of the minimum angle of resolution (logMAR). The mean BCVA improved to 0.37±0.16logMAR (p=0.008) and 0.20±0.13logMAR (p=0.001) after 1 and 3months, respectively. At the last follow-up visit (6-month follow-up), the mean BCVA was 0.21±0.15logMAR (p=0.002). The mean foveal thickness at baseline (513.8μm, range, 319–720μm) decreased significantly (308.0μm; range, 263–423μm) by the end of the follow-up period (p<0.0001). Final foveal thickness was significantly correlated with baseline BCVA (r=0.57, p=0.002). No ocular or systemic adverse events were observed. ConclusionsShort-term results suggest that the intravitreal dexamethasone implant is safe and well tolerated in patients with pseudophakic cystoid macular edema. Treated eyes had revealed a significant improvement in BCVA and decrease in macular thickness by optical coherence tomography.

Intravitreal ranibizumab for the treatment of fibrovascular pigment epithelial detachment in age-related macular degeneration

ObjectiveTo determine the response of predominantly fibrovascular pigment epithelial detachments (PED)–type lesions (secondary to age-related macular degeneration [AMD]) to intravitreal ranibizumab. DesignThis was an open-label prospective study. ParticipantsThirty-two patients with predominantly fibrovascular PED-type lesions secondary to AMD were included in this study. Three patients were excluded from the final analysis. MethodsPatients received monthly intravitreal ranibizumab injections for 6 months (induction). At 6 months, patients not experiencing a visual improvement from baseline Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity or not showing a reduction in PED height (based on optical coherence tomography [OCT]) were deemed ranibizumab nonresponders and received no further injections but underwent re-evaluation at 12 months. Patients deemed responders continued with OCT-guided active treatment on an as-needed basis for an additional 6 months. ResultsTwenty-four patients (82.8%) were ranibizumab responders and 5 were (17.2%) nonresponders. For ranibizumab responders, mean ETDRS visual acuity improved by 7.2 ± 9.8 letters at 6 months (p = 0.002) and 6.3 ± 8.6 letters at 12 months (p = 0.002). Ranibizumab nonresponders experienced a decline in mean visual acuity of 8.2 ± 4.6 letters at 6 months (p = 0.02) and 18.2 ± 10.11 letters at 12 months (p = 0.02). At baseline, responders had a mean PED height of 345.8 ± 96.0 μm, which decreased to 111.6 ± 133.2 μm at 6 months (p < 0.001) and had a slight increase at 12 months to 144.8 ± 146.3 μm (p < 0.001). Two responders (8.3%) and 2 nonresponders (40%) developed retinal pigment epithelium tears while on treatment. ConclusionsIntravitreal ranibizumab appears to be a well-tolerated treatment option for patients with fibrovascular PED. Further large-scale, prospective studies may assist in delineating the best treatment protocol.

Combined photodynamic therapy and intravitreal ranibizumab injection for polypoidal choroidal vasculopathy

Objective To observe the efficacy and safety of combined photodynamic therapy (PDT)with intravitreal ranibizumab injection in patients with polypoidal choroidal vasculopathy (PCV).Methots Twenty-four PCV patients (24 eyes) were enrolled in this retrospective case study.All patients were assessed by the examinations of Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart,color fundus photography,fundus fluorescein angiography (FFA),indocyanine green angiography (ICGA) and optic coherence tomography (OCT).The mean visual acuity was (33.41± 19.43) letters; the mean macular retinal thickness was (343.63 ± 88.60) μm.Patients received PDT first,and intravitreal injected ranibizumab 0.5 mg (0.05 ml) 72 hours later.Treatments were repeated as a single intravitreal injection of ranibizumab combined with or without PDT if the monthly follow-up indicated that it was necessary.The average follow-up period was 13.1 months.The average treatment times were analyzed for each eye.Systemic and ocular adverse events were observed.Visual acuity,macular retinal thickness and leakage of PCV before and after the treatment were analyzed.Results Intravitreal ranibizumab injections was repeated (2.8± 1.6) times per eye on average,and intravitreal injection of ranibizumab combined with PDT was repeated (0.4±0.5) times per eye on average.No systemic and ocular adverse effects were found during and after combined therapy.In the last follow-up,the mean visual acuity of ETDRS was (44.21±17.24)letters,improved by 10.8 letters (t=-4.77,P＜0.01).Visual acuity was improved in 11 eyes (45.8％) and stable in 13 eyes (54.2％).FFA and ICGA showed complete closed PCV in 17 eyes (70.8％),partial closed PCV in 7 eyes (29.2％).OCT image showed that the retinal edema was disappeared in 19 eyes (79.2％) and alleviated in 5 eyes (20.8％).The mean macular retinal thickness was (171.33±38.06) μm,which was 172.30 μm less than that of pre-treatment values (t =11.96,P＜ 0.05).Conclusion Photodynamic therapy combined with intravitreal ranibizumab injections for PCV is safe and effective,with visual acuity improvement,reduction of retinal edema and PCV leakage. Key words: Choroid diseases/therapy; Photochemotherapy; Antibodies, monoclonal

A pilot study of an acupuncture protocol to improve visual function in retinitis pigmentosa patients

BackgroundPatients with retinitis pigmentosa are motivated to try complementary or integrative therapies to slow disease progression. Basic science, clinical research and retinitis pigmentosa patients' self‐reports support the hypothesis that acupuncture may improve visual function.MethodsA prospective, case series, pilot study enrolled 12 adult patients with RP treated at an academic medical centre with a standardised protocol that combined electroacupuncture to the forehead and below the eyes and acupuncture to the body, at 10 half‐hour sessions over two weeks. Pre‐ and post‐treatment tests included Early Treatment Diabetic Retinopathy Study visual acuity (VA), Pelli‐Robson contrast sensitivity (CS), Goldmann visual fields, and dark‐adapted full‐field stimulus threshold (FST)(n = 9). Scotopic Sensitivity Tester‐1 (SST‐1) dark‐adaptometry was performed on the last two subjects.ResultsSix of 12 subjects had measurable, significant visual function improvements after treatment. Three of nine subjects tested with the FST had a significant 10.3 to 17.5-dB (that is, 13‐ to 53‐fold) improvement in both eyes at one week after acupuncture, maintained for at least 10 to 12 months, which was well outside typical test‐retest variability (95% CI: 3–3.5-dB) previously found in retinitis pigmentosa. SST‐1 dark‐adaptation was shortened in both subjects tested on average by 48.5 per cent at one week (range 36 to 62 per cent across 10 to 30-dB), which was outside typical coefficients of variation of less than 30 per cent previously determined in patients with retinitis pigmentosa and normals. Four of the five subjects with psychophysically measured scotopic sensitivity improvements reported subjective improvements in vision at night or in dark environments. One subject had 0.2 logMAR improvement in VA; another had 0.55 logCS improvement. Another subject developed more than 20 per cent improvement in the area of the Goldmann visual fields. The acupuncture protocol was completed and well tolerated by all, without adverse events or visual loss.ConclusionsAcupuncture entails minimal risk, if administered by a well‐trained acupuncturist and may have significant, measurable benefits on residual visual function in patients with retinitis pigmentosa, in particular scotopic sensitivity, which had not previously been studied. These preliminary findings support the need for future controlled studies of potential mechanisms.

The neovascular age-related macular degeneration database: multicenter study of 92 976 ranibizumab injections: report 1: visual acuity.

To study real-world ranibizumab therapy for treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) and to benchmark standards of care. Multicenter, national nAMD database study. A total of 92 976 treatment episodes from 12 951 eyes of 11 135 patients. Up to 5 years of routinely collected, anonymized data were extracted remotely from 14 United Kingdom centers to a central database using an electronic medical record (EMR) system. Participating centers used ranibizumab to treat nAMD using a loading phase of 3 monthly injections and a pro re nata retreatment regimen. The minimum data set defined before first patient data entry and mandated by the EMR system included age, Early Treatment Diabetic Retinopathy Study visual acuity (VA) at all visits, and injection episodes. Baseline VA, change in VA, number of treatments and clinic visits, and baseline characteristics affecting VA change. Information from more than 300 000 clinic visits (2.8 million data points) were collated. Mean age at first treatment was 79.1 years, with a female preponderance of 1.7:1. Mean VA (letters) for eyes followed up for at least 3 years from a baseline of 55 letters was 57 (+2) letters at 1 year, 56 (+1) letters at 2 years, and 53 (-2) letters at 3 years. The proportion of eyes that avoided moderate vision loss at years 1, 2, and 3 were 90%, 84%, and 82%, respectively. The proportion of eyes with VA of 20/40 or better were: baseline, 16%; year 1, 30%; year 2, 30%; and year 3, 29%. The median number of treatments for eyes followed up for at least 3 years in years 1, 2 and 3 was 5, 4, and 4, respectively, and the median number of outpatient visits was 9.2, 8.2, and 8.2, respectively. Baseline VA was related inversely to mean vision gain at 3 months. Older age was associated with lower presenting VA. Real-world visual outcomes achieved at a large number of centers across the United Kingdom do not match the results achieved in most randomized trials, but they were delivered with substantially fewer injections and hospital visits. This study provides important benchmark results that should be of interest to patients, retina specialists, and commissioners of health care. This study demonstrates the EMR system's potential usefulness for future phase 4 and 5 clinical trials.

Functional Burden of Strabismus

Binocular summation (BiS) is defined as the superiority of visual function for binocular over monocular viewing. Binocular summation decreases with age and large interocular differences in visual acuity. To our knowledge, BiS has not heretofore been well studied as a functional measure of binocularity in strabismus. To evaluate the effect of strabismus on BiS using a battery of psychophysical tasks that are clinically relevant and easy to use and to determine whether strabismus is associated with binocular inhibition in extreme cases. Case-control study. University-based eye institute. Strabismic patients recruited during 2010 to 2012 from a preoperative clinic and control participants with no history of eye disease other than refractive error. A battery of psychophysical and electrophysiological tests including Early Treatment Diabetic Retinopathy Study visual acuity, Sloan low-contrast acuity (LCA) (2.5% and 1.25%), Pelli-Robson contrast sensitivity, and sweep visual evoked potential contrast sensitivity. Binocular summation was calculated as the ratio between binocular and better-eye individual scores. Sixty strabismic and 80 control participants were prospectively examined (age range, 8-60 years). Mean BiS was significantly lower in the strabismic patients than controls for LCA (2.5% and 1.25%, P = .005 and <.001, respectively). For 1.25% LCA, strabismic patients had a mean BiS score less than 1, indicating binocular inhibition (ie, the binocular score was less than that of the better eye's monocular score). There was no significant difference in BiS for contrast thresholds on Early Treatment Diabetic Retinopathy Study visual acuity, Pelli-Robson contrast sensitivity, or sweep visual evoked potential contrast sensitivity. Regression analysis revealed a significant worsening of BiS with strabismus for 2.5% (P = .009) and 1.25% (P = .002) LCA, after accounting for age. Strabismic patients demonstrate subnormal BiS and even binocular inhibition for LCA, suggesting that strabismus impairs visual function more than previously appreciated. This may explain why strabismic patients who are not diplopic close 1 eye in visually demanding situations. This finding clarifies the visual deficits impacting quality of life in strabismic patients and may represent a novel measure by which to evaluate and monitor function in strabismus.

Residual colour detection abilities in age-related macular degeneration

ObjectiveTo quantify residual abilities to identify a target’s colour in cases with age-related macular degeneration (AMD). MethodsSubjects with AMD with best corrected visual acuity (BCVA) of 20/50 to 20/400 in the better eye (test eye) and age older than 55 years were recruited. A separate matching control group was recruited with subjects with BCVA of 20/40 or better. Each subject was presented sequentially with square-shaped colour targets corresponding in size to optotype sizes used in standard Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocols, all against a white background. Four major colour hues were selected for testing: blue, yellow, green, and red. The same subjects were tested with standard ETDRS targets (black on white), and results served as control group references. The primary outcome measure selected for analysis was the minimum angle of resolution (MAR) required to correctly identify the hue presented. ResultsForty study subjects (14 males and 26 females) aged 55 to 95 years (mean 79.45 years, SD 8.82) were recruited. Thirty similar subjects were recruited for a control group. Red on white estimates were better than for other colours and related best to standard black on white ETDRS estimates (20/121 vs 20/132, respectively). Also, red on white estimates seem not to be affected by age. Estimates for colour detection for the control group were not different among colours tested and were not affected by age. ConclusionsRanking abilities according to the MAR required to identify a hue can serve as a quantifying measure for residual colour vision. Our findings reflect functional abilities rather than psychophysical measurements.

The Effect of the Oral PKC β Inhibitor Ruboxistaurin on Vision Loss in Two Phase 3 Studies

To assess the effect of ruboxistaurin (RBX) on vision loss through a prospectively defined combined analysis of two phase 3 trials (MBDL and MBCU). Patients in both of these 3-year randomized, placebo-controlled, double-masked trials had best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) ≥ 75 letters (∼20/32 Snellen), ETDRS retinopathy level 20 to 47D (MBDL) or 35B to 53E (MBCU), and no prior panretinal or focal photocoagulation in at least one eye at baseline. Patients received oral placebo (N = 508 total from both studies) or RBX 32 mg/d (N = 520 total). Best-corrected ETDRS VA was measured at 6-month intervals for 3 years (MBDL) or for 18 to 48 months (MBCU). Sustained moderate visual loss (SMVL) was defined as a 15-letter or more reduction from baseline in VA sustained for a patient's last 6 months of study participation. In the combined studies (N = 1028 total), SMVL occurred in 4.4% of placebo- versus 2.3% of RBX-treated patients (P = 0.069). In patients with a minimum of 2 years of follow-up (N = 825 total), there was less SMVL in the RBX group (4.4% placebo versus 2.1% RBX, P = 0.045). Other VA-related measures (mean VA, contrast sensitivity, Visual Functioning Questionnaire 25 [VFQ-25]) either trended toward a benefit for RBX or were also statistically significant in favor of RBX. In contrast, diabetic macular edema (DME) morphology-related measures (occurrence of significant center of macula involvement, optical coherence tomography [OCT]-determined center of macula thickness, application of focal photocoagulation) did not show a consistent trend in favor of or against RBX. SMVL data in a prospectively defined combined analysis from these two phase 3 trials suggest a magnitude of effect of RBX on vision loss similar to that seen in two prior studies (approximately 50% reduction above standard care). However, event rates were low and statistical significance was not achieved. (ClinicalTrials.gov numbers, NCT00133952, NCT00090519.).

INTRAVITREAL BEVACIZUMAB FOR EXTRAFOVEAL CHOROIDAL NEOVASCULARIZATION SECONDARY TO PATHOLOGIC MYOPIA

To assess the effects of intravitreal bevacizumab injections in the treatment of extrafoveal choroidal neovascularization (CNV) associated with pathologic myopia. Patients diagnosed with pathologic myopia complicated by extrafoveal CNV were considered in this prospective, open-label interventional study. All patients underwent a complete ophthalmologic examination, including Early Treatment Early of Diabetic Retinopathy Study (ETDRS) visual acuity measurement, optical coherence tomography, and fluorescein angiography. The protocol treatment included a first injection, followed by repeated injections over a 24-month follow-up period on the basis of optical coherence tomography and angiographic features, monitored monthly. Primary outcomes were the mean changes in best-corrected visual acuity and the proportion of eyes gaining at least 15 letters at the 24-month examination. Secondary outcomes included central macular thickness, size of the CNV, and extension to the fovea. Fifteen patients were included in the study. Mean best-corrected visual acuity changed from 0.47 logarithm of the minimum angle of resolution (20/60 Snellen equivalent) at baseline to 0.22 logarithm of the minimum angle of resolution (20/30 Snellen equivalent) at the 24-month examination. An improvement of at least 3 ETDRS lines was achieved by 7 eyes (46.6%) at the 24-month examination. Mean central macular thickness changed from 313 μm to 254 μm at the 24-month examination (P = 0.008). Mean CNV size decreased from 348 μm2 to 251 μm2 at 24 months (P = 0.029). Intravitreal bevacizumab injection is a beneficial treatment for extrafoveal CNV associated with pathologic myopia.

Ranibizumab Treatment Outcomes in Phakic versus Pseudophakic Eyes: An Individual Patient Data Analysis of 2 Phase 3 Trials

<h3>Objective</h3> To compare visual outcomes in phakic and pseudophakic eyes treated with monthly intravitreal ranibizumab for exudative age-related macular degeneration (AMD). <h3>Design</h3> Meta-analysis of individual patient data from 2 phase 3 clinical trials of intravitreal ranibizumab in neovascular AMD (Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration [ANCHOR], ClinicalTrials.gov number, NCT00061594; and Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related Macular Degeneration [MARINA], ClinicalTrials.gov number NCT00056836). <h3>Participants and Controls</h3> A total of 1137 patients from 2 phase 3 clinical trials. <h3>Methods</h3> Phakic and pseudophakic eyes were treated with monthly intravitreal ranibizumab (0.3 mg or 0.5 mg), sham injections plus verteporfin photodynamic therapy (ANCHOR), or sham injections alone (MARINA). <h3>Main Outcome Measures</h3> Mean change from baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) and the proportion of patients gaining or losing 15 or more ETDRS letters. <h3>Results</h3> After adjusting for baseline covariates, no differences were seen in mean change in VA for phakic versus pseudophakic eyes. Pseudophakic eyes were more likely to lose 15 or more letters of vision than phakic eyes at 12 months, but not at 24 months. <h3>Conclusions</h3> Overall, in this analysis, lens status did not demonstrate an independent influence on mean VA for eyes treated with monthly ranibizumab. It is possible that phakic eyes may be less prone to severe vision loss. <h3>Financial Disclosure(s)</h3> Proprietary or commercial disclosure may be found after the references.

Longitudinal Relationships among Visual Acuity and Tasks of Everyday Life: The Salisbury Eye Evaluation Study

To study the relationships among visual and physical function trajectories of aging adults. The community-based random sample consists of 2520 adults who were aged 65 to 84 years in 1993 to 1995 and reassessed 2, 6, and 8 years later. Presenting and best-corrected Early Treatment Diabetic Retinopathy Study visual acuity were obtained. Activities of daily living (ADLs) and instrumental ADLs (IADLs) were evaluated through survey instruments. Growth curve models were used to simultaneously estimate health trajectories and obtain associations among the trajectories while controlling for relevant covariates. Best-corrected acuity (logMAR) worsened by an average of 0.013 (∼1 letter) annually. ADL difficulties increased by 0.22 standard deviations (SD) and IADL difficulties increased by 0.28 SD annually. Controlling for demographic and health covariates, visual acuity rates of decline correlated with rates of increase in ADL difficulties (r = 0.15, P = 0.05) and IADL difficulties (r = 0.41, P < 0.001). Acuity loss was significantly related to increases in ADLs for men (b = 0.039, P < 0.01), but not for women (b = 0.001, P > 0.9). The direct effects of acuity loss were strongest for IADLs where a 1-unit decline in acuity (logMAR) was associated with a 0.067 SD increase in IADL difficulties (P < 0.001) at baseline, and a 1-unit acuity decline (logMAR) per year resulted in a 0.10 SD unit increase in the rate of change in IADL difficulties (P < 0.001) per year. Over time, increases in visual acuity loss were related to increased IADL difficulties in men and women and increases in ADL difficulties for men only. The findings support the importance of maintaining vision in older adults.

Correlation of Recognition Visual Acuity With Posterior Retinal Structure in Advanced Retinopathy of Prematurity

OBJECTIVE To compare Early Treatment Diabetic Retinopathy Study visual acuity outcome with retinal structural outcome at the 6-year follow-up examination of infants randomized in the Early Treatment for Retinopathy of Prematurity study. METHODS We compared the results in 606 eyes of subjects in whom both functional (visual acuity) and retinal structural assessments were obtained at age 6 years. Visual acuity assessments were performed by masked testers, and retinal examinations were performed by certified ophthalmologists. MAIN OUTCOME MEASURES Visual acuity and retinal structure at age 6 years. RESULTS Concordant outcomes occurred in 462 eyes (76.2%): 402 eyes had favorable functional and structural outcomes and 60 eyes had unfavorable functional and structural outcomes. Discordant outcomes occurred in 92 eyes (15.2%): 86 eyes had unfavorable functional and favorable structural outcomes and 6 eyes had favorable functional and unfavorable structural outcomes. Of the 86 eyes with unfavorable functional and favorable structural outcomes, 43 had optic atrophy (23 eyes) and/or retinal abnormalities that were less severe than those considered to be unfavorable (32 eyes). In 52 eyes (8.6%), retinal structure could not be assessed or the visual acuity was untestable. CONCLUSION Posterior pole appearance correlates well with visual acuity in 6-year-old infants with a history of advanced retinopathy of prematurity. APPLICATION TO CLINICAL PRACTICE When the retinal structure is normal but visual acuity is poor in infants with a history of severe retinopathy of prematurity, other diagnoses such as optic atrophy and cortical visual impairment could at least partially account for the discrepancy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00027222.

About This Journal

To compare Early Treatment Diabetic Retinopathy Study visual acuity outcome with retinal structural outcome at the 6-year follow-up examination of infants randomized in the Early Treatment for Retinopathy of Prematurity study. We compared the results in 606 eyes of subjects in whom both functional (visual acuity) and retinal structural assessments were obtained at age 6 years. Visual acuity assessments were performed by masked testers,and retinal examinations were performed by certified ophthalmologists. Visual acuity and retinal structure at age 6 years. Concordant outcomes occurred in 462 eyes(76.2%): 402 eyes had favorable functional and structural outcomes and 60 eyes had unfavorable functional and structural outcomes. Discordant outcomes occurred in 92 eyes (15.2%): 86 eyes had unfavorable functional and favorable structural outcomes and 6 eyes had favorable functional and unfavorable structural outcomes.Of the 86 eyes with unfavorable functional and favorable structural outcomes, 43 had optic atrophy (23 eyes) and/or retinal abnormalities that were less severe than those considered to be unfavorable (32 eyes). In 52 eyes (8.6%), retinal structure could not be assessed or the visual acuity was untestable. Posterior pole appearance correlates well with visual acuity in 6-year-old infants with a history of advanced retinopathy of prematurity.

Macular Epiretinal Brachytherapy in Treated Age-related Macular Degeneration (MERITAGE): Month 12 Optical Coherence Tomography and Fluorescein Angiography

To report the optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) results of the Macular Epiretinal Brachytherapy in Treated Age-Related Macular Degeneration study. Prospective, multicenter, interventional, noncontrolled clinical trial. Fifty-three eyes of 53 participants with chronic, active neovascular age-related macular degeneration (AMD) requiring frequent anti-vascular endothelial growth factor retreatment. Participants underwent pars plana vitrectomy with a single 24-gray dose of epimacular brachytherapy (EMB), delivered with an intraocular, handheld, cannula containing a strontium 90/yttrium 90 source positioned over the active lesion. Participants were retreated with ranibizumab administered monthly as needed, using predefined retreatment criteria. Patients underwent FFA at baseline, month 1, and month 12. Patients underwent optical coherence tomography (OCT) at baseline and then monthly for 12 months. The FFA and OCT images were evaluated by independent, central reading facilities. Change in OCT centerpoint thickness and angiographic lesion size 12 months after EMB. Mean centerpoint thickness increased by 50 μm, from 186 to 236 μm (P = 0.292), but 70% of participants had an increase of less than the mean, with a median increase of only 1.8 μm. The FFA total lesion size increased slightly by 0.79 mm(2), from 14.69 to 15.48 mm(2) (P = 0.710). Total choroidal neovascularization (CNV) area increased by 1.17 mm(2), from 12.94 to 14.12 mm(2) (P = 0.556). The classic CNV area decreased substantially by 3.70 mm(2), from 3.90 to 0.20 mm(2) (P<0.01). Predominantly classic lesions showed the greatest response, with mean Early Treatment Diabetic Retinopathy Study visual acuity improving by 1.5 letters (versus -4.0 for all participants combined); mean centerpoint thickness decreased by 43 μm (P = 0.875). The angiographic and OCT response did not correlate with lesion size at baseline. In chronic, active, neovascular AMD, EMB is associated with nonsignificant changes in centerpoint thickness and FFA total lesion size over 12 months.

INTRAVITREAL INJECTION OF RANIBIZUMAB DURING CATARACT SURGERY IN PATIENTS WITH DIABETIC MACULAR EDEMA

To investigate macular thickness and visual acuity changes after 1 intravitreal injection of 0.5-mg ranibizumab during phacoemulsification cataract surgery in eyes with diabetic macular edema refractory to laser treatment. Eleven eyes of 11 patients with diabetic macular edema refractory to modified Early Treatment Diabetic Retinopathy Study laser therapy received intravitreal during phacoemulsification cataract surgery. Comprehensive ophthalmic evaluation was performed preoperatively and at 1, 4, 8 ± 1, and 12 ± 2 weeks postoperatively. Main outcome measures included central subfield thickness and best-corrected Early Treatment Diabetic Retinopathy Study visual acuity. Eleven patients completed the 12-week study visit. Mean central subfield thickness (± SEM) was 399.82 ± 29.50 μm at baseline and did not change significantly at any postoperative study visit (P > 0.05). Mean (± SEM) best-corrected Early Treatment Diabetic Retinopathy Study visual acuity was 0.95 ± 0.13 logarithm of the minimum angle of resolution (20/200) at baseline and was significantly improved at Weeks 1 (0.38 ± 0.13), 4 (0.38 ± 0.11), 8 (0.35 ± 0.08), and 12 (0.46 ± 0.12) after treatment (P < 0.05). In this case series of patients with diabetic macular edema refractory to laser therapy, intravitreal ranibizumab administered during cataract surgery was associated with no significant change in central subfield thickness postoperatively. Significant improvement in best-corrected Early Treatment Diabetic Retinopathy Study visual acuity was observed after treatment, likely because of cataract removal.