William R Freeman

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

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Publications (413)1488.9 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Many chorioretinal diseases are chronic and need sustained drug delivery systems to keep therapeutic drug level at the disease site. Many intravitreal drug delivery systems under developing do not have mechanism incorporated for a non-invasive monitoring of drug release. Current study prepared rugate porous silicon (pSi) particles by electrochemical etching with the currents frequency (K value) of 2.17 and 2.45. Two model drugs (Rapmycin and Dexamethasone) and two drug-loading strategies were tested for the feasibility to monitor drug release from the pSi particles through a color fundus camera. The pSi particles (k=2.45) with infiltration loading of rapamycin demonstrated progressively more violet color reflection which was negatively associated with the rapamycin released into the vitreous (r=-0.4, p<0.001, pairwise). In contrast, pSi with K value of 2.17 demonstrated progressive color change towards green and a weak association between rapmycin released into vitreous and green color abundance was identified (r=-0.23, p=0.002, pairwise). Dexamethasone was covalently loaded on to the fully oxidized pSi particles that appeared in vitreous as yellow color and fading over time. The yellow color decrease over time was strongly associated with the dexamethasone detected from the vitreous samples (r=0.7, p<0.0001, pairwise). These results suggest that engineered porous silicon particles may be used as a self-reporting drug delivery system for a non-invasive real time remote monitoring. Copyright © 2015. Published by Elsevier Ltd.
    Acta biomaterialia 06/2015; DOI:10.1016/j.actbio.2015.06.012 · 5.68 Impact Factor
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    ABSTRACT: Proliferative vitreoretinopathy (PVR) is the most common cause of poor visual outcomes in association with retinal detachment surgeries and ocular trauma. Daunorubicin (DNR) has shown the strongest efficacy in proliferation inhibition in vitro. However, clinical studies showed only mild effect due to limitations of narrow therapeutic window and short vitreous half-life. Three milligrams of DNR-loaded particles were intravitreally injected into 18 pigmented rabbits and vitreous samples were collected up to 84 days for analysis. Thirty-seven rabbits were used for a dose-escalation (1, 3, 6 mg) safety and efficacy study in rabbit PVR model using a pre-treatment design. Loading efficiency of DNR was 108.55±12μg per 1mg of the particles. Eighty four days of follow-up did not reveal any adverse reaction. Pharmacokinetic analysis demonstrated a vitreous half-life of 29 days with a maximum DNR concentration of 178 ng/ml and a minimum concentration of 29 ng/ml at day 84. DNR-loaded pSi particles were dosed 8 to 9 weeks before PVR induction and PVR severity score was dose dependent (Spearman ρ=-0.25, p=0.0005). PVR with tractional retinal detachment counted for 88% in the control group, 63% in the low dose group, 14% in the medium dose group, and 0% in the high dose group (Cochran-Armitage Trend Test, Z=8.99, ρ=-0.67, p<0.0001). DNR-loaded pSi particles can safely reside in the vitreous for at least 3 months. pSi based delivery rendered therapeutic window of DNR expanded by a factor of 862 and driven down the minimum effective concentration by a factor of 175. Copyright © 2015 by Association for Research in Vision and Ophthalmology.
    Investigative ophthalmology & visual science 03/2015; 56(4). DOI:10.1167/iovs.15-16526 · 3.66 Impact Factor
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    ABSTRACT: To characterise the presence of a hyperautofluorescent (HAF) ring associated with choroidal neovascularisation (CNV) complex in patients with wet age-related macular degeneration (AMD). Fundus autofluorescence images and spectral-domain optical coherence tomography (OCT) scans from 362 eyes with wet AMD were reviewed. The presence and size of an HAF ring associated with the CNV complex was evaluated. A subgroup of 64 treatment-naive eyes with new-onset CNV was studied to analyse the relationship between pretreatment OCT characteristics and the presence of the HAF ring. An HAF ring was present in 38% of the entire cohort of eyes and in 39% of treatment-naive eyes. The presence of the HAF ring was significantly correlated with the extent of baseline subretinal fluid (SRF) on OCT (p=0.0113), the number of antivascular endothelial growth factor (VEGF) injections (p=0.0439) and the number of treatment cycles (p=0.0154). Eyes with an HAF ring were more likely to have disruption of the ellipsoid zone line once the SRF was resolved compared with eyes without an HAF ring (p=0.0002). In multivariate analysis, the best predictors for HAF ring were the baseline area of SRF (p=0.0449) and the number of anti-VEGF treatments received (p=0.0568). Nearly 40% of wet AMD eyes had an HAF ring. In treatment-naive eyes, the HAF ring had a significant association with SRF and was found as early as the baseline measurement and as long as 18 months after beginning treatment, persisting for up to 6 years after the initial diagnosis. Its association with baseline SRF and disruption of the ellipsoid zone line of the photoreceptors on OCT could indicate continuous stress on the outer retinal structures after exposure to prolonged SRF and/or transmitted autofluorescence from loss of the photoreceptors overlying the retinal pigment epithelium. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    The British journal of ophthalmology 03/2015; DOI:10.1136/bjophthalmol-2014-306226 · 2.81 Impact Factor
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    ABSTRACT: Purpose: To understand the relationship between rapamycin loading/release and surface chemistries of porous silicon (pSi) to optimize pSi based intravitreal delivery system. Methods: Three types of surface chemical modifications are studied: (1) pSi-COOH, containing 10-carbon aliphatic chains with terminal carboxyl groups grafted via hydrosilylation of undecylenic acid; (2) pSi-C12, containing 12-carbon aliphatic chains grafted via hydrosilylation of 1-dodecene; and (3) pSiO2-C8, prepared by mild oxidation of the pSi particles followed by grafting of 8-hydrocarbon chains to the resulting porous silica surface via a silanization. Results: The efficiency of rapamycin loading follows the order (µg of drug/mg of carrier): pSiO2-C8 (105±18) > pSi-COOH (68±8) > pSi-C12 (36±6). Powder X-ray diffraction data showed that loaded rapamycin was amorphous and dynamic drug release study showed that the availability of the free drug was increased by 6-fold (compared with crystalline rapamycin) by using pSiO2-C8 formulation (p=0.0039). Of the three formulations in this study, pSiO2-C8-RAP showed optimal performance in terms of simultaneous release of the active drug andcarrier degradation, and drug loading capacity. Released rapamycin was confirmed with the fingerprints of the mass spectrometry and biologically functional as the control of commercial crystalline rapamycin. Single intravitreal injections of 2.9¬±0.37mg pSiO2-C8-RAP into rabbit eyes resulted in more than 8 weeks of residence in the vitreous while maintaining clear optical media and normal histology of the retina in comparison to the controls. Conclusion: Porous silicon based rapamycin delivery system using the pSiO2-C8 formulation demonstrated good ocular compatibility and may provide sustained drug release for retina. Copyright © 2015 by Association for Research in Vision and Ophthalmology.
    Investigative Ophthalmology &amp Visual Science 01/2015; 56(2). DOI:10.1167/iovs.14-15997 · 3.66 Impact Factor
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    ABSTRACT: There still is an unmet need for a safe and sustained intravitreal drug delivery system. In this study we are proposing and characterizing a micelle based, clear-media intravitreal drug delivery system using the lipid derivatized nucleoside analog, hexadecyloxypropyl-cidofovir (HDP-CDV, CMX 001). HDP-CDV forms micelles in water and in vitreous supernatant with the critical micelle concentration of 19 μg/mL and 9 μg/mL, respectively at 37°C. The formed micelles had the average size of 274.7 nm and the Zeta potential of -47.1 mV. Drug release study in the excised rabbit vitreous showed a sustained release profile with a half-life of 2.7 days. The micelle formulation of HDP-CDV demonstrated a good safety profile in two animal species (rabbit and guinea pig) following intravitreal injection. The sustained efficacy was tested in a pretreatment study design and the drug potency was tested in an ongoing herpes simplex virus (HSV-1) retinitis model. The pretreatment studies using single intravitreal injection and later HSV-1 infection revealed at least 9 weeks of vitreous presence and therapeutic level of HDP-CDV, with 71% eyes protection from infection. The treatment study demonstrated that intravitreal administration halted active HSV-1 retinitis in 80% of the infected eyes while cidofovir (CDV) treatment failed to suppress active HSV-1 retinitis. In summary, lipid derivatized nucleoside analogs can be formulated as a micelle intravitreal injection and provides a sustained drug release in vitreous for chronic retinal diseases.
    European Journal of Pharmaceutics and Biopharmaceutics 12/2014; 89. DOI:10.1016/j.ejpb.2014.12.010 · 4.25 Impact Factor
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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; DOI:10.1016/j.ajo.2014.11.022 · 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.
    Experimental Eye Research 11/2014; 129C:74-82. DOI:10.1016/j.exer.2014.11.002 · 3.02 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; 28(10). DOI:10.1038/eye.2014.189 · 1.90 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; 35(1). DOI:10.1097/IAE.0000000000000268 · 3.18 Impact Factor
  • Jama Ophthalmology 07/2014; 132(7):902-904. DOI:10.1001/jamaophthalmol.2014.419 · 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.
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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 05/2014; 9(5):e97023. DOI:10.1371/journal.pone.0097023 · 3.53 Impact Factor
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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; 10(8). DOI:10.1016/j.actbio.2014.04.024 · 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; 98(8). DOI:10.1136/bjophthalmol-2013-304488 · 2.81 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; DOI:10.1097/IAE.0000000000000120 · 3.18 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; 178. DOI:10.1016/j.jconrel.2014.01.003 · 7.26 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; DOI:10.1097/IAE.0000000000000015 · 3.18 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; DOI:10.1097/IAE.0000000000000025 · 3.18 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; DOI:10.1097/IAE.0000000000000003 · 3.18 Impact Factor
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    ABSTRACT: HIV retinopathy is the most common non-infectious complication in the eyes of HIV-positive individuals. Oncotic lesions in the retinal nerve fiber layer, referred to as cotton wool spots (CWS), and intraretinal (IR) hemorrhages are frequently observed but are not unique to this pathology. HIV-positive patients have impaired color vision and contrast sensitivity, which worsens with age. Evidence of inner-retinal lesions and damage have been documented ophthalmoscopically, however their long term structural effect has not been investigated. It has been hypothesized that they may be partially responsible for loss of visual function and visual field. In this study we utilized clinical data, retinal imaging and transcriptomics approaches to comprehensively interrogate non-infectious HIV retinopathy. The methods employed encompassed clinical examinations, fundus photography, indirect ophthalmoscopy, Farmsworth-Munsell 100 hue discrimination testing and Illumina BeadChip analyses. Here we show that changes in the outer retina, specifically in the retinal pigment epithelium (RPE) and photoreceptor outer segments (POS) contribute to vision changes in non-infectious HIV retinopathy. We find that in HIV-positive retinae there is an induction of rhodopsin and other transcripts (including PDE6A, PDE6B, PDE6G, CNGA1, CNGB1, CRX, NRL) involved in visual transduction, as well as structural components of the rod photoreceptors (ABCA4 and ROM1). This is consistent with an increased rate of renewal of rod outer segments induced via increased phagocytosis by HIV-infected RPE previously reported in culture. Cone-specific transcripts (OPN1SW, OPN1LW, PDE6C, PDE6H and GRK7) are uniformly downregulated in HIV positive retina, likely due to a partial loss of cone photoreceptors. Active cotton wool spots and intraretinal hemorrhages (IRH) may not affect photoreceptors directly and the interaction of photoreceptors with the aging RPE may be the key to the progressive vision changes in HIV-positive patients.
    PLoS ONE 09/2013; 8(9):e74712. DOI:10.1371/journal.pone.0074712 · 3.53 Impact Factor

Publication Stats

7k Citations
1,488.90 Total Impact Points


  • 1988–2015
    • University of California, San Diego
      • • Department of Ophthalmology
      • • Department of Electrical and Computer Engineering
      • • Department of Medicine
      San Diego, California, United States
  • 2013
    • University of Milan
      • Department of Clinical Sciences and Community Health
      Milano, Lombardy, Italy
  • 2000–2013
    • Ludwig-Maximilians-University of Munich
      • Eye Clinic
      München, Bavaria, Germany
    • University of San Diego
      San Diego, California, United States
  • 2001–2012
    • National University (California)
      San Diego, California, United States
  • 1997–2012
    • La Jolla Pharmaceutical
      San Diego, California, United States
  • 2008
    • Yonsei University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2007
    • Inje University
      • College of Medicine
      Kimhae, South Gyeongsang, South Korea
  • 2006
    • Yonsei University
      • Department of Ophthalmology
      Sŏul, Seoul, South Korea
    • Celal Bayar Üniversitesi
      • Department of Ophthalmology
      Saruhan, Manisa, Turkey
  • 2004
    • University of California, Los Angeles
      Los Ángeles, California, United States
  • 2002
    • University of Illinois at Chicago
      Chicago, Illinois, United States
  • 1993–2000
    • University of Texas Health Science Center at San Antonio
      • Department of Ophthalmology
      San Antonio, TX, United States
  • 1998
    • University of Leuven
      Louvain, Flemish, Belgium
  • 1995
    • University of Pittsburgh
      • Department of Pathology
      Pittsburgh, Pennsylvania, United States