W R Freeman

University of California, San Diego, San Diego, California, United States

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Publications (409)1380.03 Total impact

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    ABSTRACT: To evaluate 6-month and 1-year outcomes of every 8 weeks (Q8W) aflibercept in patients with resistant neovascular age-related macular degeneration (AMD). Retrospective, interventional, consecutive case series. Retrospective review of patients with resistance (multiple recurrences or persistent exudation) to every 4 weeks (Q4W) ranibizumab or bevacizumab that were switched to Q8W aflibercept. Sixty-three eyes of 58 patients had a median of 13 (interquartile range (IQR), 7-22) previous anti Vascular Endothelial Growth Factor (anti-VEGF) injections. At 6-months after changing to aflibercept, 60.3% of eyes were completely dry, which was maintained up to one-year. The median maximum retinal thickness improved from 355 microns to 269 microns at 6 months (p<0.0001) and 248 microns at one year (p<0.0001). There was no significant improvement in ETDRS visual acuity at 6 months (p=0.2559) and one-year follow-up (p=0.1081) compared with baseline. The mean difference in ETDRS visual acuity compared to baseline at 6 months was -0.05 logMAR (+2.5 letters) and 0.04 logMAR at 1 year (-2 letters). Sixty percent of eyes with resistant AMD while on Q4W ranibizumab or bevacizumab were completely dry after changing to Q8W aflibercept at the 6-month and 1-year follow-ups, but visual acuity did not significantly improve. Only a third of eyes needed to be switched from Q8W to Q4W aflibercept due to persistence of fluid; Q8W dosing of aflibercept without the initial 3 monthly loading doses may be a good alternative in a select group of patients who may have developed ranibizumab or bevacizumab resistance. Copyright © 2014 Elsevier Inc. All rights reserved.
    American Journal of Ophthalmology 11/2014; · 4.02 Impact Factor
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    ABSTRACT: Dexamethasone is a glucocorticoid that is widely used in the ophthalmic arena. The recent FDA approved dexamethasone implant can provide a three month efficacy but with high rate of drug related cataract and high intraocular pressure (IOP). It seems that higher steroid in aqueous humor and around lens may be associated with these complications based on clinical fact that higher IOP was observed with intravitreal triamcinolone acetonide (TA) than with subtenon TA. We hypothesize that placing a sustained dexamethasone release system near back of the eye through a fine needle can maximize efficacy while mitigate higher rate of IOP rise and cataract. To develop a sustained intravitreal dexamethasone delivery system, porous silicon dioxide (pSiO2) microparticles were fabricated and functionalized with amines as well as carboxyl groups. Dexamethasone was conjugated to pSiO2 through the Steglich Esterification Reaction between hydroxyl of dexamethasone and carboxyl groups on the pSiO2. The drug loading was confirmed by Fourier transform infrared spectroscopy (FTIR) and loading efficiency was quantitated using thermogravimetric analysis (TGA). In vitro release was conducted for three months and dexamethasone was confirmed in the released samples using liquid chromatography-tandem mass spectrometry (LC/MS/MS). A pilot ocular safety and determination of vitreous drug level was performed in rabbit eyes. The drug loading study demonstrated that loading efficiency was from 5.96% to 10.77% depending on the loading reaction time, being higher with longer loading reaction time before reaching saturation around 7 days. In vitro drug release study revealed that dexamethasone release from pSiO2 particles was sustainable for over 90 days and was 80 days longer than free dexamethasone or infiltration-loaded pSiO2 particle formulation in the same setting. Pilot in vivo study demonstrated no sign of ocular adverse reaction in rabbit eyes following a single 3 mg intravitreal injection and free drug level at 2-week was 107.23 ± 10.54 ng/mL that is well above the therapeutic level but only around 20% level of dexamethasone released from OZURDEX(®) (dexamethasone intravitreal implant) in a rabbit eye model. In conclusion, dexamethasone is able to covalently load to the pSiO2 particles and provide sustained drug release for at least 3 months in vitro. Intravitreal injection of these particles were well tolerated in rabbit eyes and free drug level in vitreous at 2-week was well above the therapeutic level. Copyright © 2014. Published by Elsevier Ltd.
    Experimental Eye Research 11/2014; 129C:74-82. · 3.03 Impact Factor
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    ABSTRACT: PurposeTo evaluate visual function variations in eyes with age-related macular degeneration (AMD) compared to normal eyes under different light/contrast conditions using a time-dependent visual acuity testing instrument, the Central Vision Analyzer (CVA).Methods Overall, 37 AMD eyes and 35 normal eyes were consecutively tested with the CVA after assessing best-corrected visual acuity (BCVA) using ETDRS charts. The CVA established visual thresholds for three mesopic environments (M1 (high contrast), M2 (medium contrast), and M3 (low contrast)) and three backlight-glare environments (G1 (high contrast, equivalent to ETDRS), G2 (medium contrast), and G3 (low contrast)) under timed conditions. Vision drop across environments was calculated, and repeatability of visual scores was determined.ResultsBCVA significantly reduced with decreasing contrast in all eyes. M1 scores for BCVA were greater than M2 and M3 (P<0.001); G1 scores were greater than G2 and G3 (P<0.01). BCVA dropped more in AMD eyes than in normal eyes between M1 and M2 (P=0.002) and between M1 and M3 (P=0.003). In AMD eyes, BCVA was better using ETDRS charts compared to G1 (P<0.001). The drop in visual function between ETDRS and G1 was greater in AMD eyes compared to normal eyes (P=0.004). Standard deviations of test-retest ranged from 0.100 to 0.139 logMAR.Conclusion The CVA allowed analysis of the visual complaints that AMD patients experience with different lighting/contrast time-dependent conditions. BCVA changed significantly under different lighting/contrast conditions in all eyes, however, AMD eyes were more affected by contrast reduction than normal eyes. In AMD eyes, timed conditions using the CVA led to worse BCVA compared to non-timed ETDRS charts.Eye advance online publication, 1 August 2014; doi:10.1038/eye.2014.189.
    Eye (London, England) 08/2014; · 1.97 Impact Factor
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    ABSTRACT: To analyze intraocular pressure (IOP) response after 20-mg decanted intravitreal triamcinolone acetonide followed by early prophylactic IOP-lowering therapy.
    Retina (Philadelphia, Pa.) 07/2014; · 2.93 Impact Factor
  • Jama Ophthalmology 07/2014; 132(7):902-904. · 3.83 Impact Factor
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    ABSTRACT: Purpose:To determine the prevalence and incidence of epiretinal membranes (ERM) in eyes with inactive extramacular cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS). Methods:A case-control report from a longitudinal multicenter observational study the Studies of the Ocular Complications of AIDS (SOCA) Research Group.357 eyes of 270 patients with inactive CMV retinitis and 1084 eyes of 552 patients with no ocular opportunistic infection (OOI) were studied. Stereoscopic views of the posterior pole from fundus photographs were assessed at baseline and year 5 visits for the presence of the macular ERM. Generalized estimating equations (GEE) logistic regression was used to compare the prevalence and 5-year incidence of ERM in eyes with and without CMV retinitis at enrollment. Crude and adjusted logistic regression was performed adjusting for possible confounders. Main outcome measures included the prevalence, incidence, estimated prevalence and incidence odds ratios. Results:The prevalence of ERM at enrollment was 14.8% (53/357) in eyes with CMV retinitis vs. 1.8 % (19/1084) in eyes with no OOI. The incidence of ERM at 5 years was 18.6% (16/86) in eyes with CMV retinitis vs. 2.4% (6/253) in eyes with no OOI. The crude odds ratio (OR) [95% CI] for prevalence was 9.8, [5.5 - 17.5] (p<0.01). The crude OR [95% CI] for incidence was 9.4, [3.2 - 27.9] (p<0.01). Conclusions: A history of extramacular CMV retinitis is associated with increased prevalence and incidence of ERM formation compared to eyes without ocular opportunistic infections in AIDS patients.
    Investigative ophthalmology & visual science. 06/2014;
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    ABSTRACT: A water-soluble anthracycline antibiotic drug (daunorubicin, DNR) was loaded into oxidized porous silicon (pSiO2) microparticles and then encapsulated with a layer of polymer (poly lactide-co-glycolide, PLGA) to investigate their synergistic effects in control of DNR release. Similarly fabricated PLGA-DNR microspheres without pSiO2, and pSiO2 microparticles without PLGA were used as control particles. The composite microparticles synthesized by a solid-in-oil-in-water (S/O/W) emulsion method have mean diameters of 52.33±16.37 μm for PLGA-pSiO2_21/40-DNR and the mean diameter of 49.31±8.87 μm for PLGA-pSiO2_6/20-DNR. The mean size, 26.00±8 μm, of PLGA-DNR was significantly smaller, compared with the other two (p<0.0001). Optical microscopy revealed that PLGA-pSiO2-DNR microsphere contained multiple pSiO2 particles. In vitro release experiments determined that control PLGA-DNR microspheres completely released DNR within 38days and control pSiO2-DNR microparticles (with no PLGA coating) released DNR within 14 days, while the PLGA-pSiO2-DNR microspheres released DNR for 74 days. Temporal release profiles of DNR from PLGA-pSiO2 composite particles indicated that both PLGA and pSiO2 contribute to the sustained release of the payload. The PLGA-pSiO2 composite displayed a more constant rate of DNR release than the pSiO2 control formulation, and it displayed a significantly slower release of DNR than either the PLGA or pSiO2 formulations. We conclude that this system may be useful in managing unwanted ocular proliferation when formulated with anti-proliferation compounds such as DNR.
    Acta biomaterialia 04/2014; · 5.68 Impact Factor
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    ABSTRACT: To evaluate the efficacy of a standardised combination therapy for clinically significant diabetic macular oedema using bevacizumab injections followed by navigated laser photocoagulation to stabilise retinal thickness. In this pilot study we retrospectively reviewed charts and imaging of 23 eyes treated with the standardised combination regimen. Eyes initially received monthly bevacizumab injections, followed by navigated laser photocoagulation when central retinal thickness (CRT) was <440 µm. Patients were then followed monthly for 12 months. At the time of navigated laser after bevacizumab treatment mean vision gain was +10.4 Early Treatment Diabetic Retinopathy Study letters (p<0.01) and CRT reduction was 146 µm (p<0.001). At 12 months from baseline, the vision gain remained stable at +10.6 Early Treatment Diabetic Retinopathy Study letters (p<0.01), and CRT reduction was stable at 137 µm (p<0.001). At 12 months from laser, the vision gain was 7.8 letters from baseline (p<0.01), with no significant change compared with the gain at 12 months from baseline (p=0.108). At 12 months from laser, CRT reduction was 125 µm from baseline (p<0.001), with no significant change compared with CRT reduction at 12 months from baseline (p=0.601). Total injections needed were 4.4 from baseline to month 12, with 1.3 reinjection needed after laser. 57% of the eyes didn't require injections after laser, while 43% needed two additional injections. Standardised combination therapy using bevacizumab injections followed by navigated laser treatment for clinically significant diabetic macular oedema demonstrated significant visual gain and CRT reduction after bevacizumab treatment and stabilisation after navigated laser up to 12 months. The number of injections required in 12 months was lower than reported in previous combination studies.
    The British journal of ophthalmology 04/2014; · 2.92 Impact Factor
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    ABSTRACT: To compare laser photocoagulation plans for diabetic macular edema (DME) using fluorescein angiography (FA) versus optical coherence tomography (OCT) thickness map superimposed on the retina. Fourteen eyes with DME undergoing navigated laser photocoagulation with navigated photocoagulator had FA taken using the same instrument. Optical coherence tomography central retinal thickness map was imported to the photocoagulator and with same magnification aligned onto the retina. Three retina specialists placed laser spot marks separately on FA and OCT image in a masked fashion. The spots placed by each physician were compared between FA and OCT and among physicians. The area of dye leakage on FA and increased central retinal thickness on OCT of the same eye were also compared. The average number of spots using FA and OCT template was 36.64 and 40.61, respectively (P = 0.0201). The average area of dye leakage was 7.45 mm, whereas the average area of increased central retinal thickness on OCT of the same eye was 10.92 mm (P = 0.013). There is variability in the treatment planning for macular photocoagulation with a tendency to place more spots when guided by OCT than by FA. Integration of OCT map aligned to the retina may have an impact on treatment plan once such information is available.
    Retina (Philadelphia, Pa.) 04/2014; · 2.93 Impact Factor
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    ABSTRACT: Daunorubicin (DNR) is an effective inhibitor of an array of proteins involved in neovascularization, including VEGF and PDGF. These growth factors are directly related to retina scar formation in many devastating retinal diseases. Due to the short vitreous half-life and narrow therapeutic window, ocular application of DNR is limited. It has been shown that a porous silicon (pSi) based delivery system can extend DNR vitreous residence from a few days to 3 months. In this study we investigated the feasibility of altering the pore size of the silicon particles to regulate the payload release. Modulation of the etching parameters allowed control of the nano-pore size from 15nm to 95nm. In vitro studies showed that degradation of pSiO2 increased with increasing pore size and the degradation of pSiO2 was approximately constant for a given particle type. The degradation of pSiO2 with 43nm pores was significantly greater than the other two particles with smaller pores, judged by observed and normalized mean Si concentration of the dissolution samples (44.2±8.9 vs 25.7±5.6 or 21.2±4.2μg/mL, p<0.0001). In vitro dynamic DNR release revealed that pSiO2-CO2H:DNR (Porous silicon dioxide with covalent loading of daunorubicin) with large pores (43nm) yielded a significantly higher DNR level than particles with 15 or 26nm pores (13.5±6.9ng/mL vs. 2.3±1.6ng/mL and 1.1±0.9ng/mL, p<0.0001). After two months of in vitro dynamic release, 54% of the pSiO2-CO2H:DNR particles still remained in the dissolution chamber by weight. In vivo drug release study demonstrated that free DNR in vitreous at post-injection day 14 was 66.52ng/mL for 95nm pore size pSiO2-CO2H:DNR, 10.76ng/mL for 43nm pSiO2-CO2H:DNR, and only 1.05ng/mL for 15nm pSiO2-CO2H:DNR. Pore expansion from 15nm to 95nm led to a 63 folds increase of DNR release (p<0.0001) and a direct correlation between the pore size and the drug levels in the living eye vitreous was confirmed. The present study demonstrates the feasibility of regulating DNR release from pSiO2 covalently loaded with DNR by engineering the nano-pore size of pSi.
    Journal of Controlled Release 01/2014; · 7.63 Impact Factor
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    ABSTRACT: Visual function abnormalities are common in people living with HIV disease (PLWH) without retinitis, even after improvement in immune status. Abnormalities such as reduced contrast sensitivity, altered color vision, peripheral visual field loss, and electrophysiological changes are related to a combination of retinal dysfunctions, involving inner and outer retinal structures. The standard protocol for testing vision performance in clinical practice is the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. However, this method poorly correlates with activities of daily living that require patients to assess visual stimuli in multiple light/contrast conditions, and with limited time. We utilized a novel interactive computer program (Central Vision Analyzer) to analyze vision performance in PLWH under a variety of light/contrast conditions that simulate stressful and real-world environments. The program tests vision in a time-dependent way that we believe better correlates with daily living activities than the non-timed ETDRS chart. We also aimed to correlate visual scores with retinal neuro-fiber layer thickness on optical coherence tomography. Here we show that visual acuity is more affected in PLWH in comparison to HIV-seronegative controls in varying contrast and luminance, especially if the nadir CD4+ T-cell count was lower than 100 cells/mm3. Visual impairment reflects the loss of retinal nerve fiber layer thickness especially of the temporal-inferior sector. In PLWH the ETDRS chart test led to better visual acuity compared to the Central Vision Analyzer equivalent test, likely because patients had indefinite time to guess the letters. This study confirms and strengthens the finding that visual function is affected in PLWH even in absence of retinitis, since we found that the HIV serostatus is the best predictor of visual loss. The Central Vision Analyzer may be useful in the diagnosis of subclinical HIV-associated visual loss in multiple light/contrast conditions, and may offer better understanding of this entity called "neuroretinal disorder".
    PLoS ONE 01/2014; 9(5):e97023. · 3.53 Impact Factor
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    ABSTRACT: To compare the choroidal volume (CV) between emmetropic and highly myopic eyes, and to assess if the presence of myopic fundus abnormalities, myopic traction maculopathy, or choroidal neovascularization affects the CV. We retrospectively reviewed imaging studies of 98 eyes of 98 patients who underwent CV measurement on optical coherence tomography. We included 31 emmetropic eyes (Group 1), 36 highly myopic eyes without vitreoretinal or choroidal pathologies (Group 2), 21 highly myopic eyes with traction maculopathy (Group 3), and 10 highly myopic eyes with history of choroidal neovascularization (Group 3). Eyes with chorioretinal atrophy were excluded. Regression analysis was performed to evaluate the correlation between CV and multiple variables. Choroidal volume was lower in Group 2 than in Group 1 (P < 0.001), and in Groups 3 and 4 than in Group 2 (P < 0.001 and P = 0.002, respectively). Age (P = 0.002), axial length (P < 0.001), sex (P = 0.047), staphyloma (P < 0.001), and myopic group (P = 0.05) were independent predictors for the final CV (R = 0.645). In highly myopic eyes, CV decreased by 0.32 mm for every 10 years and by 0.49 mm per millimeter of axial length. Choroidal thinning is present in highly myopic eyes compared with emmetropic eyes, and is related to age, axial length, sex, and staphyloma. However, myopic eyes with coexisting myopic traction maculopathy or history of choroidal neovascularization have more severe thinning, likely leading to insufficient metabolic supplementation for the macula.
    Retina (Philadelphia, Pa.) 11/2013; · 2.93 Impact Factor
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    ABSTRACT: To describe the vitreoretinal interface of the asymptomatic fellow eyes of patients with acute unilateral posterior vitreous detachment (PVD) based on biomicroscopic examination and spectral domain optical coherence tomography. Sixty-five eyes of 65 consecutive patients with acute unilateral PVD were examined by slit-lamp, indirect ophthalmoscopy, and spectral domain optical coherence tomography. The state of PVD in different retinal locations and premacular pocket were assessed and graded using spectral domain optical coherence tomography. Nine eyes (13.85%) had no PVD, 15 (23.08%) had extrafoveal vitreous separation (Stage 1), 18 (27.69%) had partial foveal vitreous separation (Stage 2), 12 (18.46%) had complete foveal vitreous separation (Stage 3), and 11 (16.92%) had a complete PVD (Stage 4). The presence of a premacular pocket showed equal distribution in Stages 0, 1, and 2 (66.67, 80.00, and 77.78%, respectively) but was significantly less common in Stages 3 (P = 0.016) and 4 (P < 0.0001). Only certain posterior vitreous configurations were identified (P < 0.0001), suggesting an orderly progression of PVD evolution. Our spectral domain optical coherence tomography-based PVD staging system describes the evolution of PVDs. This can be used as a guide in predicting the occurrence and evolution of PVD in this population.
    Retina (Philadelphia, Pa.) 10/2013; · 2.93 Impact Factor
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    ABSTRACT: To evaluate the morphologic restoration of retinal anatomy after surgery for epiretinal membrane (ERM) peeling using spectral domain optical coherence tomography. Correlation of retinal structure with visual outcome. Retrospective consecutive case series. Thirty-four consecutive eyes with ERM underwent surgery with 1 year follow-up examination. Spectral domain optical coherence tomography scans were analyzed preoperatively and 1, 3, 6, 9, and 12 months postoperative. Best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study charts was measured at each visit. All eyes showed a significant improvement of BCVA after ERM peeling (P = 0.002). The time point of BCVA and retinal restoration seen on spectral domain optical coherence tomography occurred simultaneously and varied between individuals (occurrence of BCVA: mean, 4.82 months; retinal restoration: mean, 4.24 months). At 3 months, the retinal anatomical restoration rate was 70% and 88% at 6 months. Restoration of the retinal anatomical structure predominantly occurs within the first 3 months post-ERM peeling. An improvement of BCVA and anatomical retinal restoration after ERM removal varies in individuals. If retinal layers fully restore in their anatomical structure, BCVA improves at the same time point.
    Retina (Philadelphia, Pa.) 09/2013; · 2.93 Impact Factor
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    ABSTRACT: Porous silicon (pSi) microparticles have been investigated for intravitreal drug delivery and demonstrated good biocompatibility. With the appropriate surface chemictry, pSi can reside in vitreous for months or longer. However, ocular distribution and clearance pathway of its degradation product, silicic acid, are not well understood. In the current study, rabbit ocular tissue was collected at different time point following fresh pSi (day 1, 5, 9, 16, and 21) or oxidized pSi (day 3, 7, 14, 21, and 35) intravitreal injection. In addition, dual-probe simultaneous microdialysis of aqueous and vitreous humor was performed following a bolus intravitreal injection of 0.25 mL silicic acid (150 μg/mL) and six consecutive microdialysates were collected every 20 minutes. Silicon was quantified from the samples using inductively coupled plasma-optical emission spectroscopy. The study showed that following the intravitreal injection of oxidized pSi, free silicon was consistently higher in the aqueous than in the retina (8.1±6.5 vs. 3.4±3.9 μg/mL, p= 0.0031). The area under the concentration-time curve (AUC) of the retina was only about 24% that of the aqueous. The mean residence time was 16 days for aqueous, 13 days for vitreous, 6 days for retina, and 18 days for plasma. Similarly, following intravitreal fresh pSi, free silicon was also found higher in aqueous than in retina (7±4.7 vs. 3.4±4.1 μg/mL, p= 0.014). The AUC for the retina was about 50% of the AUC for the aqueous. The microdialysis revealed the terminal half-life of free silicon in the aqueous was 30 minutes and 92 minutes in the vitreous; the AUC for aqueous accounted for 38 % of the AUC for vitreous. Our studies indicate that aqueous humor is a significant pathway for silicon egress from the eye following intravitreal injection of pSi crystals.
    Experimental Eye Research 09/2013; · 3.03 Impact Factor
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    ABSTRACT: Visual evoked potentials (VEP) are used to confirm the function of prosthetic devices designed to stimulate retinas with damaged photoreceptors in vivo. In this work, we focus on methods and experimental consideration for recording visual evoked potential in rabbit models and assesses the use for retinal prosthesis research. We compare both invasive and noninvasive methods for recording VEPs, the response of the rabbit retina to various light wavelengths and intensities, focal vs. full field stimulation, and the effect of light bleaching on the retinal response.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 07/2013; 2013:3539-3542.
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    ABSTRACT: PURPOSE: To evaluate temporal changes and predictors of accuracy in the alignment between simultaneous near-infrared image and optical coherence tomography (OCT) scan on the Heidelberg Spectralis using a model eye. DESIGN: Laboratory investigation. METHODS: After calibrating the device, 6 sites performed weekly testing of the alignment for 12 weeks using a model eye. The maximum error was compared with multiple variables to evaluate predictors of inaccurate alignment. Variables included the number of weekly scanned patients, total number of OCT scans and B-scans performed, room temperature and its variation, and working time of the scanning laser. A 4-week extension study was subsequently performed to analyze short-term changes in the alignment. RESULTS: The average maximum error in the alignment was 15 ± 6 μm; the greatest error was 35 μm. The error increased significantly at week 1 (P = .01), specifically after the second imaging study (P < .05); reached a maximum after the eighth patient (P < .001); and then varied randomly over time. Predictors for inaccurate alignment were temperature variation and scans per patient (P < .001). For each 1 unit of increase in temperature variation, the estimated increase in maximum error was 1.26 μm. For the average number of scans per patient, each increase of 1 unit increased the error by 0.34 μm. CONCLUSION: Overall, the accuracy of the Heidelberg Spectralis was excellent. The greatest error happened in the first week after calibration, and specifically after the second imaging study. To improve the accuracy, room temperature should be kept stable and unnecessary scans should be avoided. The alignment of the device does not need to be checked on a regular basis in the clinical setting, but it should be checked after every other patient for more precise research purposes.
    American Journal of Ophthalmology 06/2013; · 4.02 Impact Factor
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    ABSTRACT: BACKGROUND: To evaluate the reproducibility of blood flow velocity measurements of individual retinal blood vessel segments using retinal function imager (RFI). METHODS: Eighteen eyes of 15 healthy subjects were enrolled prospectively at three centers. All subjects underwent RFI imaging in two separate sessions 15 min apart by a single experienced photographer at each center. An average of five to seven serial RFI images were obtained. All images were transferred electronically to one center, and were analyzed by a single observer. Multiple blood vessel segments (each shorter than 100 μm) were co-localized on first and second session images taken at different times of the same fundus using built-in software. Velocities of corresponding segments were determined, and then the inter-session reproducibility of flow velocity was assessed by the concordance correlation co-efficient (CCC), coefficient of reproducibility (CR), and coefficient of variance (CV). RESULTS: Inter-session CCC for flow velocity was 0.97 (95% confidence interval (CI), 0.966 to 0.9797). The CR was 1.49 mm/sec (95% CI, 1.39 to 1.59 mm/sec), and CV was 10.9%. The average arterial blood flow velocity was 3.16 mm/sec, and average venous blood flow velocity was 3.15 mm/sec. The CR for arterial and venous blood flow velocity was 1.61 mm/sec and 1.27 mm/sec respectively. CONCLUSION: RFI provides reproducible measurements for retinal blood flow velocity for individual blood vessel segments, with 10.9% variability.
    Albrecht von Graæes Archiv für Ophthalmologie 05/2013; · 1.93 Impact Factor
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    ABSTRACT: PURPOSE:: To evaluate the safety of oral fluorescein angiography (FA) and to compare its efficacy in detection of macular edema (ME) with spectral-domain optical coherence tomography (SD-OCT). METHODS:: Results of imaging studies for 1,928 eyes of 1,019 patients who had simultaneously undergone both oral FA and SD-OCT by a confocal laser ophthalmoscope were reviewed. Sensitivity in detecting ME, discrepancy rate, and "kappa" agreement were determined for both the techniques and with eyes stratified by disease diagnosis. RESULTS:: No allergic reactions occurred after oral FA. Mild gastric discomfort was noted in <1% of the patients; 1,840 eyes (95.4%) showed concordance between the two techniques, and kappa agreement was 90.3%. For ME, oral FA showed an overall sensitivity of 0.97 and SD-OCT of 0.91. Equivalent sensitivity was found in cases of wet age-related macular degeneration (0.99). Oral FA was more sensitive than SD-OCT in cases of retinovascular diseases. The SD-OCT showed higher sensitivity in cases of macular holes. Detection of ME by SD-OCT was significantly higher in cases of intense leakage on oral FA (P < 0.001). CONCLUSION:: Oral FA proved to be a safe and an adequate technique to evaluate ME. It is more sensitive than SD-OCT in detection of ME in cases of retinovascular diseases but can fail to detect ME in cases of macular holes. A noninvasive examination with simultaneous oral FA and SD-OCT may be considered to obtain a comprehensive evaluation of the presence of ME from different pathologies.
    Retina (Philadelphia, Pa.) 04/2013; · 2.93 Impact Factor
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    ABSTRACT: Abstract Purpose: To evaluate in vivo ocular safety of an intravitreal hydrosilylated porous silicon (pSi) drug delivery system along with the payload of daunorubicin (DNR). Methods: pSi microparticles were prepared from the electrochemical etching of highly doped, p-type Si wafers and an organic linker was attached to the Si-H terminated inner surface of the particles by thermal hydrosilylation of undecylenic acid. DNR was bound to the carboxy terminus of the linker as a drug-loading strategy. DNR release from hydrosilylated pSi particles was confirmed in the excised rabbit vitreous using liquid chromatography-electrospray ionization-multistage mass spectrometry. Both empty and DNR-loaded hydrosilylated pSi particles were injected into the rabbit vitreous and the degradation and safety were studied for 6 months. Results: The mean pSi particle size was 30×46×15 μm with an average pore size of 15 nm. Drug loading was determined as 22 μg per 1 mg of pSi particles. An ex vivo drug release study showed that intact DNR was detected in the rabbit vitreous. An in vivo ocular toxicity study did not reveal clinical or pathological evidence of any toxicity during a 6-month observation. Hydrosilylated pSi particles, either empty or loaded with DNR, demonstrated a slow elimination kinetics from the rabbit vitreous without ocular toxicity. Conclusions: Hydrosilylated pSi particles can host a large quantity of DNR by a covalent loading strategy and DNR can be slowly released into the vitreous without ocular toxicity, which would appear if an equivalent quantity of free drug was injected.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2013; · 1.46 Impact Factor

Publication Stats

6k Citations
1,380.03 Total Impact Points


  • 1988–2014
    • University of California, San Diego
      • • Department of Ophthalmology
      • • Department of Electrical and Computer Engineering
      • • Division of Infectious Diseases
      • • Department of Medicine
      San Diego, California, United States
  • 2013
    • University of Milan
      • Unitá Oculistica
      Milano, Lombardy, Italy
    • L V Prasad Eye Institute
      Bhaganagar, Andhra Pradesh, India
    • Eulji University
      Daiden, Daejeon, South Korea
  • 2003–2013
    • CSU Mentor
      Long Beach, California, United States
  • 2001–2012
    • National University (California)
      San Diego, California, United States
  • 1997–2012
    • La Jolla Pharmaceutical
      San Diego, California, United States
  • 2011
    • Wenzhou Medical College
      Yung-chia, Zhejiang Sheng, China
  • 2008
    • Yonsei University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
    • National Health Insurance Corporation Ilsan Hospital
      Sŏul, Seoul, South Korea
  • 2007
    • Inje University
      • College of Medicine
      Kimhae, South Gyeongsang, South Korea
  • 2006
    • Celal Bayar Üniversitesi
      • Department of Ophthalmology
      Saruhan, Manisa, Turkey
  • 2004
    • University of Florida
      • Department of Ophthalmology
      Gainesville, FL, United States
  • 1999–2003
    • Ludwig-Maximilian-University of Munich
      • Eye Clinic
      München, Bavaria, Germany
    • King Saud University
      • College of Medicine
      Riyadh, Mintaqat ar Riyad, Saudi Arabia
  • 1993–2000
    • University of Texas Health Science Center at San Antonio
      • Department of Ophthalmology
      San Antonio, TX, United States
  • 1995
    • Doheny Eye Institute
      Los Angeles, California, United States
    • University of Pittsburgh
      • Department of Pathology
      Pittsburgh, Pennsylvania, United States