Showing papers by "Adnan Tufail published in 2012"

Topographic variation and interocular symmetry of macular choroidal thickness using enhanced depth imaging optical coherence tomography.

Abstract: PURPOSE: To report and analyze factors influencing topographical and interocular variations in choroidal thickness (CT) in a healthy adult population. METHODS: One hundred eyes of 50 healthy subjects underwent visual acuity and axial length measurements and optical coherence tomography (OCT) with enhanced depth imaging (EDI). CTs at the fovea and at 3 mm nasal, temporal, superior, and inferior to the fovea were measured manually. Topographic variation, relative interocular differences in CT and predictors of CT were analyzed. The relationships between interocular differences in CT and differences in age and interocular axial length were explored. RESULTS: The mean (SD) foveal CT in the right and left eyes were 334 (95) and 333 (90) μm, respectively. For foveal CT, there was a high correlation between the two eyes (r = 0.90) with a relative interocular 95% limits of agreement of -80 to +83, and a median (range) absolute difference of 21 (0.4-135). There was no significant variation in the relative and absolute interocular differences in CT. Axial length was the main predictor of CT for nasal and foveal CT. Symmetry in CT in the horizontal and vertical meridians was seen in eyes with axial length shorter than 23.50 mm (P < 0.05). CONCLUSIONS: There was no significant relative interocular difference in CT. Axial length contributes to some of the variances in CT but has a significant influence on the CT profile. Although relative interocular difference is not significant, absolute interocular differences in CT may reach 85 μm.

Assessment of Differential Pharmacodynamic Effects Using Optical Coherence Tomography in Neovascular Age-Related Macular Degeneration

Abstract: Bevacizumab (Avastin, Genentech, South San Francisco, CA), an antiangiogenic agent licensed for the management of colorectal carcinoma, has been widely adopted for the treatment of neovascular age-related macular degeneration (AMD).1,2 Recently, the results of the Avastin (Bevacizumab) in Choroidal Neovascularization (ABC) Trial provided the first level I evidence (i.e., evidence from a well-designed, randomized, controlled clinical trial) for the safety and efficacy of this approach.3 In the ABC trial, bevacizumab was administered as an intravitreous injection once every 6 weeks, after an initial loading phase of three intravitreous injections, further treatment was determined in large part by the assessment of disease activity using optical coherence tomography (OCT). As in the ABC study, many clinical trials have adopted OCT-derived retreatment criteria, both for neovascular AMD and for other disorders.4–6 In addition, the application of OCT to clinical research has elucidated many hitherto unrecognized disease characteristics and clarified many aspects of disease pathophysiology.7 The advent of OCT has also allowed objective, quantitative assessment of morphologic parameters,8,9 with OCT-derived measurements of retinal thickness commonly used for both clinical and research purposes.10,11 As our knowledge of OCT image analysis has grown, however, it has become increasingly clear that even accurate measurements of retinal thickness may fail to predict visual outcomes.12,13 Thus, much of the focus of recent clinical imaging research has been on the identification of novel OCT-derived anatomic biomarkers.14–17 For clinical trials, the discovery of novel OCT biomarkers may provide valuable information regarding therapeutic mechanisms of action, pharmacodynamics, and pharmacokinetics.18,19 If such biomarkers are shown to predict clinical benefit, they could also serve as surrogate endpoints in these trials, potentially leading to increased accuracy, reduced costs, and shortened duration. Similarly, in clinical practice, such parameters could extend the application of OCT imaging beyond simple diagnosis and toward prognosis.7 With the increased utilization of combination treatment strategies20 and the likely future development of additional pathway-based therapies,21 such pharmacodynamic and prognostic information may soon be crucial for the clinician in choosing the appropriate type and level of care. In the ABC trial, bevacizumab was compared to the standard therapy available at the trial's initiation: pegaptanib (Macugen; OSI Pharmaceuticals, New York, NY) or verteporfin photodynamic therapy (PDT; Novartis, Basel, Switzerland).3,22 Although treatment of patients in these standard therapy groups was not determined by OCT-derived criteria, OCT examinations were nonetheless performed. Thus, the ABC trial offers a unique opportunity to investigate novel OCT biomarkers, with an emphasis on differential pharmacodynamic effects, in a phase III/IV randomized clinical trial.

Optimizing individualized therapy with bevacizumab for neovascular age-related macular degeneration.

Abstract: PURPOSE: The purpose of this study was to evaluate a standardized retreatment strategy with intravitreal bevacizumab in the treatment of neovascular age-related macular degeneration. METHODS: In this double-masked randomized trial, patients with neovascular age-related macular degeneration were randomized to intravitreous bevacizumab or standard care. Bevacizumab treatment was given at 6 weekly intervals with 3 consecutive injections (loading phase) followed by variable dosing to Week 54 using standardized retreatment criteria. RESULTS: Three hundred and eighty retreatment decisions were made after 3 fixed injections for 64 patients randomized to bevacizumab that completed 1-year follow-up. The most common criterion for retreatment was persistent intraretinal fluid on optical coherence tomography imaging, and fluorescein angiography did not drive any retreatment decision. The mean (median) change in visual acuity and optical coherence tomography central macular thickness after the 3 loading treatments to Week 54 was +0.4 (+1.0) letters and +2.0 (+1.0) μm, respectively, with a mean (median) of 7.1 (7.0) injections. The median time to retreatment was 42 days with 12 of 69 injection-free episodes (17%) lasting more than 3 months. CONCLUSION: Sustained improvements in structure and function were achieved using this 6 weekly variable-dosing regimen with intravitreal bevacizumab. Most retreatment decisions were based on qualitative interpretation of optical coherence tomography scans.

Unilateral vitelliform maculopathy: a comprehensive phenotype study with molecular screening of BEST1 and PRPH2.

Abstract: Aim To describe the clinical features of a case series of patients with unilateral vitelliform maculopathy and the results of screening BEST1 and PRPH2 for disease-causing mutations. Design/Methods This was a retrospective case series study of six patients ascertained over a 2-year period. Ophthalmological examination, fundus photography, autofluorescence imaging, optical coherence tomography and detailed electrophysiological assessment were undertaken. Blood samples were taken for DNA extraction and mutation screening of BEST1 and PRPH2 was performed. Results Six patients (3 men and 3 women) with unilateral vitelliform maculopathy were identified, ranging in age from 30 to 68 years. Vision in the affected eye ranged from 20/10 to 20/100. There was no clinical, retinal imaging or electrophysiological evidence of fellow eye involvement. Direct sequencing of BEST1 and PRPH2 did not reveal any disease-causing variants. Conclusions A case series of patients is reported with an unusual unilateral vitelliform phenotype, often associated with good visual function. The patients do not have the typical characteristics associated with age-related maculopathy or any inherited macular disorders, such as Best vitelliform macular dystrophy. Molecular screening of the candidate genes BEST1 and PRPH2 revealed no mutations.