[show abstract][hide abstract] ABSTRACT: Purpose: To describe the evaluation of optical coherence tomography (OCT) scans in the Muliticenter Uveitis Steroid Treatment (MUST) trial and report baseline OCT features of enrolled participants. Methods: Time-domain OCTs acquired by certified photographers using a standardized scan protocol were evaluated at a reading center. Accuracy of retinal thickness data was confirmed with quality evaluation, and caliper measurement of centerpoint thickness (CPT) was performed when retinal thickness data were unreliable. Morphological evaluation included cysts, subretinal fluid, epiretinal membranes (ERMs), and vitreomacular traction. Results: Of the 453 OCTs evaluated, automated retinal thickness was accurate in 69.5% of scans, caliper measurement was performed in 26%, and 4% were ungradable. Intraclass correlation was.98 for reproducibility of caliper measurement. Macular edema (centerpoint thickness ≥ 240 μm) was present in 36%. Cysts were present in 36.6% of scans and ERMs in 27.8%, predominantly central. Intergrader agreement ranged from 78 to 82% for morphological features. Conclusion: Retinal thickness data can be retrieved in a majority of OCT scans in clinical trial submissions for uveitis studies. Small cysts and ERMs involving the center are common in intermediate and posterior/panuveitis requiring systemic corticosteroid therapy.
Ocular immunology and inflammation 11/2012; · 0.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the impact of macular edema on visual acuity and visual field sensitivity in uveitis.
This study utilized baseline data from the Multicenter Uveitis Steroid Treatment (MUST) Trial, a randomized, parallel treatment clinical trial comparing alternative treatments for intermediate, posterior and panuveitis.
255 patients (481 eyes with uveitis) recruited at 23 subspecialty centers. Visual acuity, optical coherence tomography and Humphrey 24-2 visual field testing.
Macular edema was associated with impaired visual acuity (p < 0.01). Different phenotypes of macular edema were associated with different degrees of visual impairment: cystoid changes without retinal thickening were associated with moderately impaired visual acuity (-5 ETDRS letters), but visual acuity was worse in eyes with retinal thickening (-13 letters) and with both cysts and thickening (-19 letters). Uveitis sufficient to satisfy the study's inclusion criteria was associated with impaired visual field sensitivity, but eyes with macular edema had even worse visual field sensitivity (p < 0.01).
The observation that macular edema substantially reduces visual function suggests macular edema itself is an important endpoint to study in the treatment of uveitis. As uveitis and macular edema both impair visual field sensitivity as measured by Humphrey 24-2 perimetry, both should be considered when evaluating patients with uveitis and raised intraocular pressure for glaucoma.
Ocular immunology and inflammation 04/2012; 20(3):171-81. · 0.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk).
Prospective, multicenter study.
A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers.
Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status.
Patients were managed for their primary tumor and monitored for metastasis.
The GEP assay successfully classified 446 of 459 cases (97.2%). The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1%) and 44 class 2 cases (25.9%) (log-rank test, P<10(-14)). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54 of 260 tumors (20.8%) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status.
The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP.
[show abstract][hide abstract] ABSTRACT: Randomized clinical trials (RCTs) are an important component of comparative effectiveness (CE) research because they are the optimal design for head-to-head comparisons of different treatment options.
To describe decisions made in the design of the Multicenter Uveitis Steroid Treatment (MUST) Trial to ensure that the results would be widely generalizable.
Review of design and implementation decisions and their rationale for the trial.
The MUST Trial is a multicenter randomized controlled CE trial evaluating a novel local therapy (intraocular fluocinolone acetonide implant) versus the systemic therapy standard of care for noninfectious uveitis. Decisions made in protocol design in order to broaden enrollment included allowing patients with very poor vision and media opacity to enroll and including clinical sites outside the United States. The treatment protocol was designed to follow standard care. The primary outcome, visual acuity, is important to patients and can be evaluated in all eyes with uveitis. Other outcomes include patient-reported visual function, quality of life, and disease and treatment related complications.
The trial population is too small for subgroup analyses that are of interest and the trial is being conducted at tertiary medical centers.
CE trials require greater emphasis on generalizability than many RCTs but otherwise face similar challenges for design choices as any RCT. The increase in heterogeneity in patients and treatment required to ensure generalizability can be balanced with a rigorous approach to implementation, outcome assessment, and statistical design. This approach requires significant resources that may limit implementation in many RCTs, especially in clinical practice settings.
[show abstract][hide abstract] ABSTRACT: To identify a clinically meaningful threshold for change in retinal thickness measured by optical coherence tomography for patients with uveitic macular edema using correlation with change in visual acuity.
Cross-sectional and longitudinal study.
One hundred twenty-eight eyes (101 individuals) with macular edema enrolled in the Multicenter Uveitis Steroid Treatment (MUST) trial. At enrollment and after 6 months of follow-up, retinal thickness was measured at the central subfield with time-domain optical coherence tomography and visual acuity was measured with logarithmic (Early Treatment Diabetic Retinopathy Study) visual acuity charts. Participants were classified as having macular edema if the retinal thickness was 260 μm or more.
A threshold for change in retinal center subfield thickness of 20% balanced the percentage of false positives and false negatives for predicting more than a 10-letter change in visual acuity with a sensitivity of 77% and a specificity of 75%. The results were similar for more than 5-letter changes and for 15-letter or more changes. Those with a 20% or more reduction in retinal thickness had a mean 11.0-letter improvement (95% confidence interval, 7.7 to 14.3) as compared with a -0.4-letter change (95% confidence interval, -4.1 to 3.3) in visual acuity for those without a 20% reduction (P < .01).
In addition to being above the level of measurement uncertainty, a 20% change in retinal thickness in patients with macular edema seems to be optimal for clinically important changes in visual acuity and may be considered as an outcome for clinical trials of treatments for uveitic macular edema.
American Journal of Ophthalmology 08/2011; 152(6):1044-1052.e5. · 3.63 Impact Factor
[show abstract][hide abstract] ABSTRACT: To compare the relative effectiveness of systemic corticosteroids plus immunosuppression when indicated (systemic therapy) versus fluocinolone acetonide implant (implant therapy) for noninfectious intermediate, posterior, or panuveitis (uveitis).
Randomized controlled parallel superiority trial.
Patients with active or recently active uveitis.
Participants were randomized (allocation ratio 1:1) to systemic or implant therapy at 23 centers (3 countries). Implant-assigned participants with bilateral uveitis were assigned to have each eye that warranted study treatment implanted. Treatment-outcome associations were analyzed by assigned treatment for all eyes with uveitis.
Masked examiners measured the primary outcome: change in best-corrected visual acuity from baseline. Secondary outcomes included patient-reported quality of life, ophthalmologist-graded uveitis activity, and local and systemic complications of uveitis or therapy. Reading Center graders and glaucoma specialists assessing ocular complications were masked. Participants, ophthalmologists, and coordinators were unmasked.
On evaluation of changes from baseline to 24 months among 255 patients randomized to implant and systemic therapy (479 eyes with uveitis), the implant and systemic therapy groups had an improvement in visual acuity of +6.0 and +3.2 letters (P = 0.16, 95% confidence interval on difference in improvement between groups, -1.2 to +6.7 letters, positive values favoring implant), an improvement in vision-related quality of life of +11.4 and +6.8 units (P = 0.043), a change in EuroQol-EQ5D health utility of +0.02 and -0.02 (P = 0.060), and residual active uveitis in 12% and 29% (P=0.001), respectively. Over the 24 month period, implant-assigned eyes had a higher risk of cataract surgery (80%, hazard ratio [HR] = 3.3, P < 0.0001), treatment for elevated intraocular pressure (61%, HR=4.2, P < 0.0001), and glaucoma (17%, HR=4.2, P = 0.0008). Patients assigned to systemic therapy had more prescription-requiring infections than patients assigned to implant therapy (0.60 vs 0.36/person-year, P=0.034), without notable long-term consequences; systemic adverse outcomes otherwise were unusual in both groups, with minimal differences between groups.
In each treatment group, mean visual acuity improved over 24 months, with neither approach superior to a degree detectable with the study's power. Therefore, the specific advantages and disadvantages identified should dictate selection between the alternative treatments in consideration of individual patients' particular circumstances. Systemic therapy with aggressive use of corticosteroid-sparing immunosuppression was well tolerated, suggesting that this approach is reasonably safe for local and systemic inflammatory disorders.
Proprietary or commercial disclosure may be found after the references.
[show abstract][hide abstract] ABSTRACT: To compare Reading Center (RC) cup-to-disc ratio (CDR) assessment from stereoscopic photographs with clinician estimation in a uveitis clinical trial.
Clinical estimation of CDR was performed by ophthalmologists via dilated biomicroscopy. Photographic evaluation was performed at an independent RC by masked, certified evaluators. Quality control was performed by repeat grading of 77 randomly selected images.
Among 479 eyes with uveitis, 353 eyes had clinical and photographic grades for CDR. Agreement between clinical and RC grading was fair, with exact agreement of 29%. Agreement within 0.1 and 0.2 CDR was 70 and 93%, respectively (weighted κ = .34). Intergrader reproducibility at the RC was better (weighted κ = .59, ICC 0.74).
Morphologic assessment of cup to disc ratio is an important outcome and safety measure for determining glaucomatous damage in clinical trials. Masked RC measurements are more likely to be accurate than biomicroscopic grading in identifying meaningful anatomical change associated with glaucoma.
Ocular immunology and inflammation 08/2011; 19(4):267-74. · 0.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: To validate a photographic vitreous haze grading technique using a 9-step logarithmic scale in patients enrolled in a randomized, controlled clinical trial in uveitis.
Retrospective study of clinical trials methodology.
University-based department of ophthalmology.
Baseline fundus photographs of patients with intermediate uveitis, posterior uveitis, or panuveitis enrolled in the Multicenter Uveitis Steroid Treatment (MUST) trial. OBSERVATIONAL PROCEDURE: Grading of vitreous haze using a previously described photographic scale. Regrading of a subset of photographs to assess intraobserver agreement.
Interobserver and intraobserver intraclass correlation for photographic haze grading, and correlation between photographic and clinical vitreous haze scores, assessment of the clinical findings that significantly affect the photographic haze score.
Vitreous haze was graded in 271 eyes (142 patients) by 3 postgraduate ophthalmologists. The interobserver and intraobserver intraclass correlations were excellent, with correlation coefficients between 0.84 and 0.93. There was moderately strong correlation between the photographic and clinical vitreous haze scores (r=0.51; P<.001), with significant differences among the mean and median photographic haze scores for the 3 lowest clinical grades of haze, 0, 1+, and 2+. Other parameters that correlated with photographic vitreous haze score included visual acuity of 20/50 or worse (P=.003), degrees of posterior synechiae (P<.001), lens abnormality (P=.023) or posterior capsule obscuration (P=.001), and amount of anterior vitreous cell (P=.002).
Photographic grading of vitreous haze with a 9-step logarithmic scale is a highly reproducible methodology that may be adaptable to use in future clinical trials.
American journal of ophthalmology 06/2011; 152(2):170-176.e1. · 3.83 Impact Factor
[show abstract][hide abstract] ABSTRACT: To describe the procedures and reproducibility for grading stereoscopic color fundus photographs and fluorescein angiograms of participants in the SCORE Study.
Standardized stereoscopic fundus photographs and fluorescein angiograms taken at 84 clinical centers were evaluated by graders at a central reading center. Type of retinal vein occlusion (RVO), area of retinal thickening, and area of retinal hemorrhage are evaluated from fundus photographs; area of fluorescein leakage and area of capillary nonperfusion are measured on fluorescein angiography. Temporal reproducibility consisted of annual regrading of a randomly selected dedicated subset of fundus photographs (60 subjects) and fluorescein angiograms (40 subjects) for 3 successive years. Contemporaneous reproducibility involved monthly regrading of a 5% random selection of recently evaluated fundus photographs (n = 73).
The intergrader agreement for RVO type and presence of retinal thickening was greater than 90% in the 3 annual regrades. The intraclass correlation (ICC) for area of retinal thickening in the 3 years ranged from 0.39 to 0.64 and for area of retinal hemorrhage, 0.87 to 0.96. The ICC for area of fluorescein leakage ranged from 0.66 to 0.75 and for capillary nonperfusion, 0.94 to 0.97. The contemporaneous reproducibility results were similar to those of temporal reproducibility for all variables except area of retinal thickening (ICC, 0.84).
The fundus photography and fluorescein angiography grading procedures for the SCORE Study are reproducible and can be used for multicenter longitudinal studies of RVO. A systematic temporal drift occurred in evaluating area of retinal thickening.
Archives of ophthalmology 09/2010; 128(9):1140-5. · 3.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: Fluorescein angiography (FA) has been performed as part of the management of diabetic macular edema for many years. Its current role relative to the role of optical coherence tomography (OCT) is not well defined.
To evaluate the associations of FA features with visual acuity (VA) and with OCT and fundus photographic characteristics in eyes with diabetic macular edema.
In a clinical trial, conducted by the Diabetic Retinopathy Clinical Research Network to compare two methods of laser photocoagulation to treat diabetic macular edema, FA (film and digital), color photographs, OCT, and VA measurements were obtained at baseline and at 1 year. Grading of morphologic features was performed at a reading center. Reproducibility of FAs was assessed, and the correlations of FA features with VA, OCT, and color photograph features were computed.
From 79 clinical sites, data of 323 study eyes and 203 fellow nonstudy eyes were analyzed. Fluorescein leakage area at baseline was associated with reduced VA, increased OCT measures of retinal thickness and volume, and color photographic measurements of retinal thickening (r = 0.33-0.58). No important associations were found with changes from baseline to 12 months in these parameters or with any of the other variables analyzed.
Fluorescein leakage is associated with VA and some OCT and color photographic variables. We did not identify any unique FA variables that had a stronger association with VA than OCT measures of retinal thickness. These data may be useful to investigators planning future diabetic macular edema clinical trials.
[show abstract][hide abstract] ABSTRACT: The objective of this study was to perform a preliminary evaluation of the ocular and systemic safety of calcium formate, a dietary calcium supplement for prevention and management of osteoporosis. Although formate is an endogenous product of metabolism, high concentrations are associated with toxicity during methanol overdose.
In this prospective clinical trial, 12 healthy women ingested calcium formate (1,300 mg) three times a day for 14 days. Study evaluations included physical and ocular examination, extensive laboratory testing, serum calcium and formate levels, Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, color vision, visual fields, visual evoked potential (VEP), and full-field, pattern, and multifocal electroretinograms (MERG).
The mean baseline serum level of formate was 0.572 +/- 0.06 mM. Peak serum levels and final serum formate did not differ significantly from baseline. The final concentration was 0.582 +/- 0.091 mM. Accumulation of serum formate did not occur. There was also no evidence of toxicity with calcium formate ingestion. All examinations and tests remained normal, including optic nerve and retinal function. Three subjects had mild transient symptoms attributable to any calcium formulation.
Calcium formate is highly bioavailable and well-tolerated. Serum formate remained at basal levels and did not accumulate with repeated dosing. Systemic and ocular safety was demonstrated by objective testing. Given its high oral bioavailability, calcium formate may be a good choice for calcium supplementation in the prevention and management of osteoporosis. Further study will be needed to evaluate its long-term safety in a larger group of subjects representing more varied age, health, dietary, and nutritional status.
Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 07/2009; 25(3):223-30. · 1.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: To assess the safety and efficacy of intravitreous pegaptanib sodium for the treatment of macular edema following central retinal vein occlusion (CRVO).
This dose-ranging, double-masked, multicenter, phase 2 trial included subjects with CRVO for 6 months' or less duration randomly assigned (1:1:1) to receive pegaptanib sodium or sham injections every 6 weeks for 24 weeks (0.3 mg and 1 mg, n=33; sham, n=32).
Visual acuity at week 30.
In the primary analysis at week 30, 12 of 33 (36%) subjects treated with 0.3 mg of pegaptanib sodium and 13 of 33 (39%) treated with 1 mg gained 15 or more letters from baseline vs 9 of 32 (28%) sham-treated subjects (P= .48 for 0.3 mg and P= .35 for 1 mg of pegaptanib sodium vs sham). In secondary analyses, subjects treated with pegaptanib sodium were less likely to lose 15 or more letters (9% and 6%; 0.3-mg and 1-mg pegaptanib sodium groups, respectively) compared with sham-treated eyes (31%; P= .03 for 0.3 mg and P= .01 for 1 mg of pegaptanib sodium vs sham) and showed greater improvement in mean visual acuity (+7.1 and +9.9, respectively, vs -3.2 letters with sham; P= .09 for 0.3 mg and P= .02 for 1 mg of pegaptanib sodium vs sham). By week 1, the mean central retinal thickness decreased in the 0.3-mg and 1-mg pegaptanib sodium groups by 269 microm and 210 microm, respectively, vs 5 microm with sham (P< .001).
Based on this 30-week study, intravitreous pegaptanib sodium appears to provide visual and anatomical benefits in the treatment of macular edema following CRVO.
Benefits accrued with intravitreous pegaptanib sodium treatment of macular edema following CRVO suggest a role for vascular endothelial growth factor in the pathogenesis of this condition.
clinicaltrials.gov Identifier: NCT00088283.
Archives of ophthalmology 04/2009; 127(4):374-80. · 3.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: The use of intravitreal bevacizumab (Avastin) has greatly expanded since its introduction into ophthalmic care 3 years ago. A PubMed search on 1 August 2008 revealed 51 ocular disease processes that have been treated with bevacizumab. The majority of publications consist of case reports or retrospective case series and their number is increasing quickly. It is important to collate the experiences gained to date to properly inform our clinical decision making and improve the design of future clinical trials. Current studies cannot easily be combined in a meta-analysis given the lack of standardized data and the wide variety of disorders studied in small numbers. This paper will describe the attempted uses of intravitreal bevacizumab and its efficacy for each ocular disease in addition to discussing safety. Comments regarding appropriate use of this treatment are based on our current level of knowledge. It is clear that the initial encouraging results described in this paper warrant further study of intravitreal bevacizumab in larger, controlled, randomized trials.
Survey of Ophthalmology 01/2009; 54(3):372-400. · 2.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: To review the available information on classification of diabetic macular edema (DME) as focal or diffuse.
Literature review and interpretation.
The terms focal diabetic macular edema and diffuse diabetic macular edema frequently are used without clear definitions. Published definitions often use different examination methods and often are inconsistent. Evaluating published information on the prevalence of focal and diffuse DME, the responses of focal and diffuse DME to treatments, and the importance of focal and diffuse DME in assessing prognosis is hindered because the terms are used inconsistently. A newer vocabulary may be more constructive, one that describes discrete components of the concepts such as extent and location of macular thickening, involvement of the center of the macula, quantity and pattern of lipid exudates, source of fluorescein leakage, and regional variation in macular thickening and that distinguishes these terms from the use of the term focal when describing one type of photocoagulation technique. Developing methods for assessing component variables that can be used in clinical practice and establishing reproducibility of the methods are important tasks.
Little evidence exists that characteristics of DME described by the terms focal and diffuse help to explain variation in visual acuity or response to treatment. It is unresolved whether a concept of focal and diffuse DME will prove clinically useful despite frequent use of the terms when describing management of DME. Further studies to address the issues are needed.
American journal of ophthalmology 10/2008; 146(5):649-55, 655.e1-6. · 3.83 Impact Factor
[show abstract][hide abstract] ABSTRACT: To examine the structural effect of radial optic neurotomy (RON) using nasal and temporal approach incisions on the nasal side of the optic nerve (ON) using dominant and nondominant hands in human cadaver eyes.
Transvitreal RON was performed in 9 eyes with a microvitreoretinal blade by a right-handed surgeon. A nasal approach was used in 4 left eyes (using the right hand) and in 2 right eyes (using the left hand), and a temporal approach was used in 3 right eyes (using the right hand). Histologic sections were examined for depth of nerve penetration and for effect on critical structures.
The scleral canal was fully incised in all cases. The mean depth of nerve penetration was 555 micro25 microing the nasal approach and 246.7 microing the temporal approach) (P =.12). The globe was not ruptured in any eye. In a single right eye approached temporally using the right hand, the adventitial sheath of the central retinal artery was lacerated.
RON in human cadaver eyes results in lysis of the scleral canal at the ON head. Greater depth and improved safety of incision can be achieved by always approaching the incision from the nasal side of the ON using the dominant or nondominant hand.
Archives of Ophthalmology 12/2007; 125(11):1553-7. · 3.83 Impact Factor
[show abstract][hide abstract] ABSTRACT: To study effects of intravitreal pegaptanib (Macugen) on retinal neovascularization.
Retrospective analysis of a randomized clinical trial. PARTICIPANTS, INTERVENTION, AND MAIN OUTCOME MEASURES: Individuals with retinal neovascularization identified from a multicenter, randomized, controlled trial evaluating pegaptanib for treatment of diabetic macular edema, with a best-corrected visual acuity letter score between 68 and 25 (approximate Snellen equivalent between 20/50 and 20/320) and receiving a sham injection or intravitreal pegaptanib (0.3 mg, 1 mg, 3 mg) administered at study entry, week 6, and week 12, with additional injections and/or focal photocoagulation as needed during the ensuing 18 weeks, up to a maximum of 6 pegaptanib/sham therapies, were evaluated. Scatter panretinal photocoagulation before study enrollment was permitted, but not within 6 months of randomization and study entry. Changes in retinal neovascularization were assessed on fundus photographs and fluorescein angiograms graded at a reading center in a masked fashion.
Of 172 participants, 19 had retinal neovascularization in the study eye at baseline. Excluding 1 who had scatter photocoagulation 13 days before randomization and 2 with no follow-up photographs, 1 of the remaining 16 subjects had panretinal photocoagulation during study follow-up. Of these 16 subjects, 8 of 13 (62%) in a pegaptanib treatment group (including the one receiving panretinal photocoagulation), 0 of 3 in the sham group, and 0 of 4 fellow (nonstudy) eyes showed either regression of neovascularization on fundus photographs or regression or absence of fluorescein leakage from neovascularization (or both) at 36 weeks. In 3 of 8 with regression, neovascularization progressed at week 52 after cessation of pegaptanib at week 30.
Most subjects with retinal neovascularization at baseline assigned to pegaptanib showed regression of neovascularization by week 36. These findings suggest a direct effect of pegaptanib upon retinal neovascularization in patients with diabetes mellitus.
[show abstract][hide abstract] ABSTRACT: To evaluate the safety and efficacy of pegaptanib sodium injection (pegaptanib) in the treatment of diabetic macular edema (DME).
Randomized, double-masked, multicenter, dose-ranging, controlled trial.
Individuals with a best-corrected visual acuity (VA) between 20/50 and 20/320 in the study eye and DME involving the center of the macula for whom the investigator judged photocoagulation could be safely withheld for 16 weeks.
Intravitreous pegaptanib (0.3 mg, 1 mg, 3 mg) or sham injections at study entry, week 6, and week 12 with additional injections and/or focal photocoagulation as needed for another 18 weeks. Final assessments were conducted at week 36.
Best-corrected VA, central retinal thickness at the center point of the central subfield as assessed by optical coherence tomography measurement, and additional therapy with photocoagulation between weeks 12 and 36.
One hundred seventy-two patients appeared balanced for baseline demographic and ocular characteristics. Median VA was better at week 36 with 0.3 mg (20/50), as compared with sham (20/63) (P = 0.04). A larger proportion of those receiving 0.3 mg gained VAs of > or =10 letters (approximately 2 lines) (34% vs. 10%, P = 0.003) and > or =15 letters (18% vs. 7%, P = 0.12). Mean central retinal thickness decreased by 68 microm with 0.3 mg, versus an increase of 4 microm with sham (P = 0.02). Larger proportions of those receiving 0.3 mg had an absolute decrease of both > or =100 microm (42% vs. 16%, P = 0.02) and > or =75 microm (49% vs. 19%, P = 0.008). Photocoagulation was deemed necessary in fewer subjects in each pegaptanib arm (0.3 mg vs. sham, 25% vs. 48%; P = 0.04). All pegaptanib doses were well tolerated. Endophthalmitis occurred in 1 of 652 injections (0.15%/injection; i.e., 1/130 [0.8%] pegaptanib subjects) and was not associated with severe visual loss.
In this phase II trial, subjects assigned to pegaptanib had better VA outcomes, were more likely to show reduction in central retinal thickness, and were deemed less likely to need additional therapy with photocoagulation at follow-up.
[show abstract][hide abstract] ABSTRACT: To investigate the safety and efficacy of intravitreal triamcinolone acetonide as treatment for macular edema associated with central retinal vein occlusion (CRVO).
We reviewed the medical records of 13 consecutive patients (13 eyes) with macular edema associated with CRVO who were treated with an injection of intravitreal triamcinolone acetonide (4 mg) at the University of Wisconsin and the Bascom Palmer Eye Institute. Each intravitreal injection was delivered through the pars plana using a 27- or 30-gauge needle.
Change in Snellen visual acuity, clinical appearance of macular edema, measurement of foveal thickening with optical coherence tomography (OCT), and frequency of complications.
The median age of the 13 patients was 67 years (interquartile range, 57-77 years), and the median duration of symptoms before injection was 8 months (interquartile range, 4-9 months). Mean baseline visual acuity was 20/500 in the affected eye. Mean visual acuity at the 6-month follow-up examination was 20/180 in the affected eye. All 13 patients completed the 6-month examination. Eyes with nonischemic CRVO (n = 5) demonstrated a significant improvement in visual acuity, whereas eyes with ischemic CRVO (n = 8) demonstrated a nonsignificant visual acuity improvement. No patient had a decrease in visual acuity. Mean baseline foveal thickness as measured by OCT was 590 micro m (retinal thickening = 416 micro m). Mean foveal thickness as measured by OCT at the 1-month follow-up examination in 12 patients was 212 micro m (retinal thickening = 38 micro m). At the 3-month follow-up examination, mean foveal thickness as measured by OCT for 13 patients was 193 micro m (retinal thickening = 19 micro m). Between the 3- and 6-month follow-up examinations, 4 patients developed a recurrence of macular edema. Three of the 4 patients were retreated with a second injection of triamcinolone. Two of these 3 patients experienced an improvement in visual acuity following retreatment. At the 6-month follow-up examination, mean foveal thickness as measured by OCT for 13 patients was 281 micro m (retinal thickening = 107 micro m). No adverse effects such as retinal detachment or endophthalmitis occurred. One patient experienced an increase in intraocular pressure that was controlled with 2 aqueous suppressants.
Intravitreal injection of triamcinolone appears to be a possibly effective treatment in some patients with macular edema associated with CRVO. Patients with nonischemic CRVO may respond more favorably than patients with ischemic CRVO, and retreatment may be necessary in some patients. In this case series, severe complications were not noted.
Archives of Ophthalmology 09/2004; 122(8):1131-6. · 3.83 Impact Factor
[show abstract][hide abstract] ABSTRACT: Central retinal vein occlusion is one of the most common retinal vascular disorders. Many patients have decreased visual acuity as a result of macular edema. We report a retrospective review of 8 patients at the University of Wisconsin with macular edema from CRVO who were treated with an intravitreal injection of triamcinolone acetonide. Optical coherence tomography (OCT) was used to help assess the effect of this intervention. Mean baseline visual acuity was 20/500. Mean visual acuity at the 3-month follow up was 20/220. The average gain in visual acuity was 3.3 lines (range -1 to +10). Four of 8 patients experienced a visual acuity gain of 2 or more lines at the 3-month follow up. Four of 8 patients were unchanged (within 2 lines of baseline) at the 3-month follow up. No patient had a decrease in visual acuity (2 or more line decrease from baseline). Seven of 8 patients had complete resolution of macular edema on clinical examination at the 3-month follow up. No adverse effects such as cataract, glaucoma, retinal detachment or endophthalmitis were noted. We conclude that intravitreal injection of triamcinolone acetonide may be a safe and effective treatment in some patients with macular edema due to CRVO. Optical coherence tomography demonstrated significant anatomic improvement in the majority of patients with macular edema due to CRVO treated with intravitreal injection of triamcinolone acetonide.
Seminars in Ophthalmology 07/2003; 18(2):67-73. · 1.09 Impact Factor