William R Freeman

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

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Publications (452)1542.43 Total impact

  • Mostafa R. Alam · Cheryl A. Arcinue · Nadia B. Mendoza · William R. Freeman
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    ABSTRACT: Purpose: To evaluate the outcomes of different types of treatment of chronic cystoid macular edema (CME) after pars plana vitrectomy. Methods: Retrospective review of eyes that developed chronic CME after pars plana vitrectomy treated with intravitreal triamcinolone acetonide (TCA) with or without the addition of anti-vascular endothelial growth factor. Results: Thirty-nine eyes of 37 patients were included, with a median duration between pars plana vitrectomy and onset of CME of 5 months (interquartile range, 3-12). In most eyes (66.7%), the main indication for surgery was for vitreomacular interface disorders, such as epiretinal membrane, vitreomacular traction, and macular hole. With intravitreal TCA, there was a significant decrease in central foveal thickness at 3, 6, and 12 months, compared with baseline (P = 0.0171, 0.0401, and 0.0024, respectively). A significant gain in vision was noted at 1 month compared with baseline (P = 0.0169), but this was not sustained at 3, 6, and 12 months (P = 0.4862, 0.9098, and 0.4312, respectively). The addition of bevacizumab to TCA did not provide any additional benefit for central foveal thickness and visual acuity. Thirty-two eyes (82.1%) were started on prophylactic antiglaucoma drops 2 weeks after a TCA injection, and no eye needed laser or surgery to control intraocular pressure. Conclusion: Chronic CME after pars plana vitrectomy is recurrent and difficult to treat. Intravitreal TCA is effective in reducing CME, but there was only short-term visual acuity improvement even with continued reduction of central foveal thickness. Intraocular pressure did not significantly rise with the use of prophylactic antiglaucoma drops even with repeated injections.
    No preview · Article · Dec 2015 · Retina
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    ABSTRACT: Purpose: Macular pigment, composed of lutein, zeaxanthin, and meso-zeaxanthin, is postulated to protect against age-related macular degeneration, likely because of filtering blue light and its antioxidant properties. Macular pigment optical density (MPOD) is reported to be associated with macular function evaluated by visual acuity and multifocal electroretinogram. Given the importance of macular pigment, reliable and accurate measurement methods are important. The main purpose of this study is to determine the reproducibility of MPOD measurement by two-wavelength autofluorescence method using scanning laser ophthalmoscopy. Methods: Sixty-eight eyes of 39 persons were enrolled in the study, including 11 normal eyes, 16 eyes with wet age-related macular degeneration, 16 eyes with dry age-related macular degeneration, 11 eyes with macular edema due to diabetic mellitus, branch retinal vein occlusion or macular telangiectasia, and 14 eyes with tractional maculopathy, including vitreomacular traction, epiretinal membrane, or macular hole. MPOD was measured with a two-wavelength (488 and 514 nm) autofluorescence method with the Spectralis HRA + OCT after pupil dilation. The measurement was repeated for each eye 10 minutes later. The analysis of variance and Bland-Altman plot were used to assess the reproducibility between the two measurements. Results: The mean MPOD at eccentricities of 1° and 2° was 0.36 ± 0.17 (range: 0.04-0.69) and 0.15 ± 0.08 (range: -0.03 to 0.35) for the first measurement and 0.35 ± 0.17 (range: 0.02-0.68) and 0.15 ± 0.08 (range: -0.01 to 0.33) for the second measurement, respectively. The difference between the 2 measurements was not statistically significant, and the Bland-Altman plot showed 7.4% and 5.9% points outside the 95% limits of agreement, indicating an overall excellent reproducibility. Similarly, there is no significant difference between the first and second measurements of MPOD volume within eccentricities of 1°, 2°, and 6° radius, and the Bland-Altman plot showed 8.8%, 2.9%, and 4.4% points outside the 95% limits of agreement, respectively. The data for the reproducibility did not differ significantly among the various disease and normal eyes. Conclusion: Under routine examination conditions with pupil dilation, MPOD measurement by two-wavelength autofluorescence method showed a high reproducibility.
    No preview · Article · Dec 2015 · Retina
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    ABSTRACT: Purpose: To compare the real-time visualization of vitreoretino-choroidal structures using full-depth imaging (FDI) spectral domain optical coherence tomography (SD-OCT) and swept-source (SS)-OCT. Methods: Foveal scans using both FDI SD-OCT (Heidelberg Spectralis) and SS-OCT (Topcon Deep Range Imaging-OCT-1) were obtained in 40 normal eyes, 40 eyes with macular pathologies, and 40 eyes with glaucoma. Full-depth imaging SD-OCT images were obtained by manually enhancing the vitreoretinal interface first and then the choroid while averaging each OCT B-scan 100 times. Swept-source-OCT images were obtained by averaging each B-scan 96 times. After masking and randomly mixing the original OCT images, two independent physicians graded visualization of the premacular bursa, interdigitation zone line, and chorioscleral boundary, and also sharpness of choroidal structures. Results: A real-time full-depth image of vitreoretino-choroidal structures was successfully achieved with FDI SD-OCT in 118 cases (98.3%) and with SS-OCT in 45 cases (37.5%, P < 0.001). Full-depth imaging SD-OCT imaging was superior to SS-OCT imaging in visualizing the anterior border of the premacular bursa in 109 eyes (90.8%), with average grading of 1.63 ± 0.53 for the FDI SD-OCT and 0.39 ± 0.52 for the SS-OCT (P < 0.001). Swept-source-OCT was similar to FDI SD-OCT in visualizing the chorioscleral boundary in 108 eyes (90.0%), with average grading of 1.81 ± 0.39 for the SS-OCT and 1.78 ± 0.38 for the FDI-OCT (P = 0.566). The visualization of the interdigitation zone line was identical in the 2 imaging instruments (P = 1.000). The sharpness of the choroidal structures was greater with SS-OCT than with FDI-OCT (P < 0.001). Conclusion: Manual double-enhancing FDI technique using SD-OCT provided a good compromise between vitreous and retinochoroidal structures visualization in real time during scanning procedure. In contrast, SS-OCT imaged well details of choroidal sublayers. Appropriate OCT technology and software should be selected according to its application in clinical settings.
    No preview · Article · Nov 2015 · Retina (Philadelphia, Pa.)

  • No preview · Article · Nov 2015 · Retina
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    ABSTRACT: Purpose: To statistically determine differences in microcirculation patterns between nevi and uveal melanomas and the influence of these patterns on metastatic potential in the long-term follow-up of 112 patients with melanocytic uveal tumours. In vivo markers indicating malignancy and metastatic potential have implications for treatment decision. Methods: Primary diagnosis and work-up included clinical examination, fundus photography, standardized A and B scan echography as well as evaluation of tumour microcirculation patterns via confocal fluorescein and indocyanine green angiography (ICGA). Patient data were collected from the patient files, the tumour registry or personal contact. Statistical analysis was performed with spss 22.0 using chi-square, Fisher's exact test and Kaplan-Meier survival analysis. Results: Forty-three uveal melanocytic lesions remained untreated and were retrospectively classified as benign nevi, whereas 69 lesions were malignant melanomas (T1: 32, T2: 28, T3: 6 and T4: 3). 'Silent' and 'arcs without branching' were found significantly more often in nevi (p = 0.001 and p = 0.010), whereas 'parallel with cross-linking' and 'networks' were significantly more frequent in melanomas (p = 0.022 and p = 0.029). The microcirculation pattern 'parallel with cross-linking' proved significantly more frequent in patients who developed metastases (p = 0.001). Conclusions: Certain microcirculation patterns may guide us in differentiating uveal nevi from malignant melanomas. A non-invasive prognostic marker can be of great value for borderline lesions in which cytology is less likely taken. 'Parallel with cross-linking' did not only indicate malignancy, but it was also associated with later tumour metastasis.
    No preview · Article · Oct 2015 · Acta ophthalmologica
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    ABSTRACT: Aim: To review the longitudinal changes of outer retinal tubulations (ORTs) in wet age-related macular degeneration (AMD) and their response to anti-vascular endothelial growth factor (VEGF) therapy by spectral-domain optical coherence tomography (SD-OCT), and to correlate these observations with disease activity, presence or absence of fluid, and patients' demographics. Methods: Retrospective study of wet AMD eyes treated with anti-VEGF agents and showing ORTs on SD-OCT, and the patients' fellow eye with wet AMD but without ORTs. Results: Fifty-one wet AMD eyes from 31 patients diagnosed and treated for wet AMD were included in the review and analysis of data; 33 eyes showed ORTs at baseline, while 18 fellow eyes had no ORTs. During a median follow-up treatment period of 11 months, 23 eyes had stable ORTs and 10 eyes had ORT changes. Among the 10 eyes with ORTs changes, ORTs collapsed during anti-VEGF treatment in 5 eyes but then reappeared within 12 months after stopping treatment. In two eyes, ORTs increased in size during anti-VEGF treatment, while in two other eyes ORTs collapsed without any treatment. In a single eye, ORTs collapsed within 10 months of no treatment and did not reappear upon recurrence of fluid. Eyes with ORTs tended to have lower visual acuity than eyes with no ORTs due to greater disruption of the external limiting membrane in the fovea. Conclusions: ORTs documented by SD-OCT may exhibit multiple types of longitudinal changes, such as collapse, recurrence or enlargement, which could be associated with anti-VEGF treatment or spontaneous. Some ORTs may have a vascular component or may be vascular in nature, considering their response to anti-VEGF treatment, while other ORTs are likely composed only of degenerating photoreceptor cells and may collapse independently from anti-VEGF treatments.
    No preview · Article · Oct 2015 · The British journal of ophthalmology
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    ABSTRACT: Aim: To investigate patients' sensory phenomena, especially instrument visualisation, and their emotional reactions during pars plana vitrectomy (PPV) under monitored anaesthesia care (MAC). Methods: One hundred adults who underwent PPV under MAC plus peribulbar block were prospectively recruited on the day after surgery to complete a questionnaire about sensory phenomena and comfort. Anaesthetics used during surgery were correlated with visual phenomena and patient comfort. Surgeons were asked to predict patient intraoperative comfort and ability to hear. Results: Of the 27% of patients who reported visual phenomena, lights (74%), colours (37%) and moving instruments (17%) were common. Instrument visualisation was not associated with any preoperative or intraoperative variables. Visual phenomena were neutrally received by 98% of patients. Neither the use of the intravenous medications during the peribulbar injection and surgery nor the type of local anaesthesia correlated with perceived level of pain. Sixty-six per cent of patients remembered hearing surgeons talk, and 96% of patients reacted neutrally to voices. Patient reports of intraoperative pain were similar to the surgeon's prediction, and mean discomfort during surgery was mild. Conclusions: The reported prevalence of intraoperative visual phenomena is low when elicited at the first postoperative visit. Surgeons can reliably predict patients' comfort, and most patients react neutrally to visual and hearing phenomena during PPV under MAC with peribulbar block. The combination of medications used may be responsible for the neutral reception of sensory phenomena.
    No preview · Article · Sep 2015 · The British journal of ophthalmology
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    ABSTRACT: Background and Objective: To evaluate the morphological and functional outcome of wet agerelated macular degeneration (AMD) during antivascular endothelial growth factor therapy with bevacizumab using SLO microperimetry (SLO-MP) with eye tracking. Patients and Methods: First, reproducibility was tested over the choroidal neovascularization (CNV) in 21 eyes of 19 patients with wet AMD. Second, 21 eyes of 19 patients with active CNV were studied longitudinally during bevacizumab therapy. Bestcorrected visual acuity, SLO-MP, spectral-domain optical coherence tomography and fluorescein angiography were performed. Results: There was good reproducibility with a concordance correlation coefficient of 0.85. In the longitudinal study, eyes with anatomical response demonstrated a significant increase of retinal sensitivity. Non-responders showed no change in SLOMP. Retinal sensitivity at baseline had a significant predictive value for the change in retinal sensitivity during therapy with bevacizumab (P = .032). Conclusion: SLO-MP is able to analyze retinal function overlying lesions in wet AMD and can be a useful tool to monitor therapy in patients with macular diseases.
    No preview · Article · Sep 2015 · Ophthalmic Surgery Lasers and Imaging Retina
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    ABSTRACT: To use novel confocal scanning ophthalmoscopy technology to test hypothesis that HIV-seropositive patients without history of retinitis with a history of a low CD4 count are more likely to have damage to their retinal nerve fiber layer (RNFL) when compared to patients with high CD4 count. In addition, we compared optic disc morphologic changes with glaucoma. Cross-sectional study. 171 patients were divided into four groups. The control group consisted of 40 eyes of 20 HIV-seronegative patients. The second group consisted of 80 eyes of 41 HIV-positive patients whose CD4 cell count never dropped below 100 (1.0 x 109/L). The third group consisted of 44 eyes of 26 HIV-positive patients with a history of low CD4 counts <100. Fourth group consisted of 79 eyes of 79 patients with confirmed glaucoma who served as positive controls. Confocal scanning laser ophthalmoscopy was performed with the Heidelberg Retina Tomograph (HRT3) and data were analyzed with HRT3, software (Heyex version Disc area, cup area, cup volume, rim volume, mean cup depth, maximum cup depth, cup-to-disc ration, mean RNFL thickness, and RNFL cross-sectional area. Analysis of the global optic nerve and cup parameters showed no difference in disk area among the four groups. There was also no difference in cup, rim volume, mean cup depth, or maximum cup depth among the first three groups but they were all different from glaucoma group. The RNFL was thinner in glaucoma and both HIV-positive groups compared to HIV-seronegative subjects. The cross sectional RNFL area was thinner in both high and low CD4 HIV-positive groups compared to HIV-seronegative group in the nasal and temporal/inferior sectors, respectively. Glaucoma group showed thinning in all sectors. HIV retinopathy results in retinal nerve fiber layer loss without structural optic nerve supportive tissue change. RNFL damage may occur early in HIV disease by mechanism different than in glaucoma.
    Preview · Article · Aug 2015 · PLoS ONE
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    ABSTRACT: To determine the presence of structural changes in HIV retinae (i.e., photoreceptor density and retinal thickness in the macula) compared with age-matched HIV-negative controls. Cohort of patients with known HIV under CART (combination Antiretroviral Therapy) treatment were examined with a flood-illuminated retinal AO camera to assess the cone photoreceptor mosaic and spectral-domain optical coherence tomography (SD-OCT) to assess retinal layers and retinal thickness. Twenty-four eyes of 12 patients (n = 6 HIV-positive and 6 HIV-negative) were imaged with the adaptive optics camera. In each of the regions of interest studied (nasal, temporal, superior, inferior), the HIV group had significantly less mean cone photoreceptor density compared with age-matched controls (difference range, 4,308-6,872 cones/mm2). A different subset of forty eyes of 20 patients (n = 10 HIV-positive and 10 HIV-negative) was included in the retinal thickness measurements and retinal layer segmentation with the SD-OCT. We observed significant thickening in HIV positive eyes in the total retinal thickness at the foveal center, and in each of the three horizontal B-scans (through the macular center, superior, and inferior to the fovea). We also noted that the inner retina (combined thickness from ILM through RNFL to GCL layer) was also significantly thickened in all the different locations scanned compared with HIV-negative controls. Our present study shows that the cone photoreceptor density is significantly reduced in HIV retinae compared with age-matched controls. HIV retinae also have increased macular retinal thickness that may be caused by inner retinal edema secondary to retinovascular disease in HIV. The interaction of photoreceptors with the aging RPE, as well as possible low-grade ocular inflammation causing diffuse inner retinal edema, may be the key to the progressive vision changes in HIV-positive patients without overt retinitis.
    Preview · Article · Aug 2015 · PLoS ONE
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    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.
    No preview · Article · Jun 2015 · Acta biomaterialia

  • No preview · Article · Apr 2015 · American Journal of Ophthalmology
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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.
    No preview · Article · Mar 2015 · Investigative ophthalmology & visual science
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    ABSTRACT: Aim To characterise the presence of a hyperautofluorescent (HAF) ring associated with choroidal neovascularisation (CNV) complex in patients with wet age-related macular degeneration (AMD). Methods 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. Results 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). Conclusions 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.
    Full-text · Article · Mar 2015 · The British journal of ophthalmology
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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.
    No preview · Article · Jan 2015 · Investigative Ophthalmology & Visual Science
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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.
    No preview · Article · Dec 2014 · European Journal of Pharmaceutics and Biopharmaceutics
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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.
    No preview · Article · Nov 2014 · American Journal of Ophthalmology
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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.
    No preview · Article · Nov 2014 · Experimental Eye Research
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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.
    No preview · Article · Aug 2014 · Eye (London, England)
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    ABSTRACT: Purpose: To analyze intraocular pressure (IOP) response after 20-mg decanted intravitreal triamcinolone acetonide followed by early prophylactic IOP-lowering therapy. Methods: Overall, IOP results of 120 high-dose decanted intravitreal triamcinolone acetonide injections from 58 nonglaucomatous patients with macular edema, with antiglaucoma therapy prescribed from Week 1 regardless of baseline IOP were retrospectively reviewed. Results: In cases of consistent compliance with IOP-lowering drugs (79.2%), IOP increased by 2 mmHg at 4 months (P = 0.300) and returned to baseline at 6 months. In cases of noncompliance (20.8%), IOP increased by 7 mmHg at 1 month (P < 0.001) and returned to baseline after starting treatment. Multivariate regression analysis showed that nonvitrectomized eyes and noncompliance with IOP-lowering drugs were independent predictors of increase in IOP greater than 21 mmHg (P = 0.0098 and P = 0.0019, respectively). Nonvitrectomized eyes had a 46% greater chance to experience increase in IOP compared with vitrectomized ones. Poor compliance with IOP-lowering drugs lead to a 45% greater likelihood of experiencing increase in IOP compared with compliant patients. Multiple injections were not associated with the increased risk for increase in IOP greater than 21 mmHg (P = 0.273). Of 120 cases, 2 eyes (1.7%) developed uncontrolled IOP and required glaucoma surgery by 4 months, with good final IOP outcome. Conclusion: Twenty milligram decanted intravitreal triamcinolone acetonide can be safely used to treat macular edema in nonglaucomatous patients; IOP elevation can be adequately controlled with prophylactic antiglaucoma drugs. Noncompliance with prophylactic therapy creates an early spike in IOP, and vitreous status can significantly impact increase in IOP. Compliance with IOP-lowering drugs should be stressed to patients receiving high-dose intravitreal triamcinolone acetonide especially in cases of nonvitrectomized eyes.
    No preview · Article · Jul 2014 · Retina (Philadelphia, Pa.)

Publication Stats

10k Citations
1,542.43 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
  • 1997-2012
    • La Jolla Pharmaceutical
      San Diego, California, United States
    • Bascom Palmer Eye Institute
      Miami, Florida, United States
  • 2001-2007
    • National University (California)
      San Diego, California, United States
    • Wilford Hall Ambulatory Surgery Center
      Lackland Air Force Base, Texas, United States
  • 2006
    • Yonsei University
      • Department of Ophthalmology
      Sŏul, Seoul, South Korea
  • 1989-2004
    • University of California, Los Angeles
      • Department of Ophthalmology
      Los Ángeles, California, United States
  • 2000-2002
    • Ludwig-Maximilian-University of Munich
      • Eye Clinic
      München, Bavaria, Germany
    • University of Texas Health Science Center at San Antonio
      • Department of Ophthalmology
      San Antonio, TX, United States
    • University of San Diego
      San Diego, California, United States
  • 1998
    • University of Leuven
      Louvain, Flemish, Belgium
    • California College San Diego
      San Diego, California, United States
  • 1995
    • University of Pittsburgh
      • Department of Pathology
      Pittsburgh, Pennsylvania, United States