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Iryna A Falkenstein,
Lingyun Cheng,
Flossie Wong-Staal,
Ajay M Tammewar,
Erin C Barron,
Gabriel A Silva,
Qi-Xiang Li,
Dehua Yu,
Michelle Hysell,
Guohong Liu,
Ning Ke,
James E Macdonald, William R Freeman
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ABSTRACT: To investigate the intraocular properties and toxicity of IMS2186, a small molecule developed as an anti-choroidal neovascularization (anti-CNV) drug.
Cellular toxicity and mechanism of action was tested on cell lines in vitro. Intraocular studies used rabbits for drug dissolution as well as toxicity and rats for the treatment study as well as the toxicity confirmation study. Rabbits' eyes were injected with 2.5 mg of IMS2186 and observed for 36 weeks. Laser-induced CNV in rats was treated with IMS2186, Kenalog, or phosphate-buffered saline (pBS). Fluorescein angiography (FA) and immunohistochemical processing of the globes was performed.
The anti-proliferative IC(50) of IMS2186 for human fibroblast cells was 1.0-3.0 microM and 0.3-3.0 microM for human cancer cells; the IC(50) of IMS2186 to inhibit endothelial tube formation was 0.1-0.3 microM. The IC(50) of IMS2186 for inhibiting the production of pro-inflammatory cytokines was 0.3-1 microM. The IC(50) of IMS2186 for inhibiting macrophage migration was 1 micrM. These biological properties were not species specific. IMS2186 can be formulated as a suspension for long-lasting release and when delivered intraocularly, no intraocular toxicity was observed by slit lamp exam, fundus exam, intraocular pressure measurements, or by electroretinography. FA showed a reduction in the leakage in eyes treated with IMS2186 and triamcinolone acetonide; DAPI staining also showed significantly less cellularity in IMS2186-treated lesions as compared to PBS (p = 0.0025).
IMS2186 may be a safe intraocular therapeutic agent for intraocular proliferation and angiogenesis.
Current eye research 08/2008; 33(7):599-609. · 1.51 Impact Factor
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Retina 07/2008; 28(6):911-2; author reply 912. · 2.81 Impact Factor
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ABSTRACT: To assess the incidence of vitreomacular adhesion and traction in age-related macular degeneration (AMD), and to evaluate surgical treatment in a subset of patients with choroidal neovascularization (CNV) nonresponsive to anti-neovascular growth factor (anti-VEGF) treatment.
Retrospective observational case-control and interventional case series.
Spectral optical coherence tomography, combined with simultaneous scanning laser ophthalmoscope (Spectral OCT/SLO), was performed in 170 eyes of 94 elderly patients, 61 with exudative AMD, 59 with nonexudative AMD, and 50 control eyes. The presence of hyaloid adhesion to the posterior pole, and vitreomacular traction (VMT) were determined. Five patients with VMT underwent surgical hyaloid removal. Best-corrected visual acuity (BCVA) and retinal thickness were evaluated as outcomes.
Hyaloid adhesion was present in 17 eyes with exudative AMD (27.8%), 15 eyes with nonexudative AMD (25.4%), and eight control eyes (16%). Significant difference was found among the groups (P = .002). Among the eyes with hyaloid adhesion, VMT was shown in 10 eyes (59%) with exudative AMD, two eyes (13%) with nonexudative AMD, and one control eye (12%). VMT was associated with the severity of AMD (P = .0082). The area of hyaloid adhesion was significantly smaller than and concentric to the area of CNV complex in eyes with exudative AMD. Eyes with VMT that underwent surgery experienced a modest improvement of BCVA and decrease of retinal thickness.
Hyaloid adhesion to the macula is associated with AMD, and frequently causes VMT in eyes with CNV. Tractional forces may antagonize the effect of anti-VEGF treatment, and cause pharmacological resistance in a subpopulation of patients. Future studies are needed to define the role of vitreoretinal surgery in such cases. Spectral OCT/SLO allows careful diagnosis and follow-up.
American Journal of Ophthalmology 07/2008; 146(2):218-227. · 4.22 Impact Factor
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ABSTRACT: To compare high-resolution optical coherence tomography (OCT) and fluorescein angiography (FA) in detection of macular edema (ME) of various etiologies.
In a retrospective study over a 12-month period at one retina center, data for consecutive eyes that had undergone simultaneous conventional FA (HRA; Heidelberg Engineering, Vista, CA) and StratusOCT (Carl Zeiss Meditec, Dublin, CA) to rule out ME were reviewed. A subset of patients underwent additional examination with extremely high-resolution (6-microm)/ultrahigh-speed spectral OCT/scanning laser ophthalmoscopy (OTI, Inc., Toronto, Ontario, Canada).
Of 1,272 eyes, 1,208 (94.97%) had the finding of ME or subretinal fluid confirmed by both techniques. There were 49 eyes (3.86%) for which FA showed dye leakage in the macular area and OCT showed normal foveal contour. Of 10 eyes in this group that underwent imaging with ultrahigh-speed spectral OCT/scanning laser ophthalmoscopy, 8 had subtle diffuse lucencies in the retina. For 15 eyes (1.17%), OCT showed intraretinal and subretinal fluid, which was missed by FA.
Both FA and high-resolution OCT are highly sensitive techniques and correlate well in detection of ME. However, there is a small chance that when performed alone they might miss existing subtle ME.
Retina 05/2008; 28(4):538-44. · 2.81 Impact Factor
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ABSTRACT: To evaluate the influence of arteriovenous (AV) sheathotomy on retinal function with central multifocal electroretinography (mfERG) in eyes with macular edema secondary to branch retinal vein occlusion (BRVO).
Fifteen patients (15 eyes) who underwent AV sheathotomy for macular edema secondary to BRVO were included in the study. Best-corrected visual acuity and mfERG responses from the most central seven hexagons were analyzed before and 6 months after the operation.
The mean preoperative Early Treatment Diabetic Retinopathy Study (ETDRS) score +/- SD was 34.1 +/- 12.7 letters (Snellen equivalent, 20/50) and significantly improved up to 40.5 +/- 10.9 letters (Snellen equivalent, 20/40) at 6 months after AV sheathotomy (P = 0.027, Wilcoxon signed rank test). The mean preoperative P1 amplitude +/- SD of the most central 7 hexagons was 39.30 +/- 10.86 nV/deg(2) for the affected eye versus 47.72 +/- 6.67 nV/deg(2) for the normal fellow (control) eye (P = 0.013, Mann-Whitney U test) and significantly increased up to 50.71 +/- 15.58 nV/deg at 6 months after the operation (P = 0.014, Wilcoxon signed rank test). Significant correlations between preoperative and postoperative ETDRS score and preoperative P1 amplitude were present (r = 0.929, P < 0.001; r = 0.768, P = 0.001; respectively [Spearman correlation]).
AV sheathotomy improved macular function and anatomical outcome as measured by ETDRS score and mfERG responses in patients with macular edema due to BRVO.
Retina 03/2008; 28(2):220-5. · 2.81 Impact Factor
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ABSTRACT: To evaluate early changes in the central retinal response in human immunodeficiency virus (HIV)-positive patients without infectious retinitis using multifocal electroretinography (mfERG).
Case control study.
We evaluated three cohorts: HIV-negative controls and two groups of HIV-positive patients separated according to their nadir CD4 counts (>or= 100 cells/mm(3) and < 100 cells/mm(3) for a minimum of six months). mfERG first-order kernels (FOKs) and second-order kernels (SOKs) were analyzed separately by areas of rings, quadrants, and individual hexagons for each cohort.
Of 103 hexagon locations of FOK results, there were no significant differences in amplitudes of P1 and N1 across the groups (.05 < P < .50), although there was a trend for an overall reduction in the amplitudes. Similarly, latency N1 did not differ (.28 < P < .95). There were significantly delayed latencies of P1 between cohorts across 103 hexagons in both kernels. SOK results also showed significant delay in latencies of P1 and a trend of reduced P1 amplitudes across studied locations among cohorts (.24 < P < .08).
The results demonstrate widespread delay in latency in HIV-positive patients, especially in those with prolonged low (below 100 cells/mm(3)) CD4 nadir counts. These findings suggest early diffuse dysfunction of the inner retina results from severe HIV disease even in the HAART era.
American journal of ophthalmology 03/2008; 146(4):579-88. · 3.83 Impact Factor
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ABSTRACT: To evaluate the prevalence and risk factors for vision loss in patients with clinical or immunologic AIDS without infectious retinitis.
A prospective, multicenter cohort study of patients with AIDS.
One thousand three hundred and fifty-one patients (2,671 eyes) at 19 clinical trials centers diagnosed with AIDS but without major ocular complications of HIV. Standardized measurements of visual acuity, automated perimetry, and contrast sensitivity were analyzed and correlated with measurements of patients' health and medical data relating to HIV infection. We evaluated correlations between vision function testing and HIV-related risk factors and medical testing.
There were significant (P<.05) associations between measures of decreasing vision function and indices of increasing disease severity, including Karnofsky score and hemoglobin. A significant relationship was seen between low-contrast sensitivity and decreasing levels of CD4+ T-cell count. Three percent of eyes had a visual acuity worse than 20/40 Snellen equivalents, which was significantly associated with a history of opportunistic infections and low Karnofsky score. When compared with external groups with normal vision, 39% of eyes had abnormal mean deviation on automated perimetry, 33% had abnormal pattern standard deviation, and 12% of eyes had low contrast sensitivity.
This study confirms that visual dysfunction is common in patients with AIDS but without retinitis. The most prevalent visual dysfunction is loss of visual field; nearly 40% of patients have some abnormal visual field. There is an association between general disease severity and less access to care and vision loss. The pathophysiology of this vision loss is unknown but is consistent with retinovascular disease or optic nerve disease.
American Journal of Ophthalmology 03/2008; 145(3):453-462. · 4.22 Impact Factor
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ABSTRACT: To compare the measurements of visual acuity (VA) results measured with Snellen and Early Treatment Diabetic Retinopathy Study (ETDRS) charts in eyes with and without age-related macular degeneration (AMD).
Cross-sectional study.
One hundred four participants (190 eyes) selected from a university retina practice; 80 participants (142 eyes) had some degree of AMD.
Visual acuity was measured in each patient using standard procedure with both Snellen and ETDRS charts in random order. Statistical analysis of the results was performed.
Difference in VA measured by both charts in logarithm of minimal angle of resolution (logMAR) notations.
Overall, the mean Snellen VA was 0.78 logMAR (= 20/120), and the mean ETDRS VA in the same eye was 0.54 logMAR (= 20/70; P<0.001). In the low vision group (<20/200), represented by patients with AMD, the average difference in number of lines was considerably larger than in the good vision range (>20/30). On average, 20/200 on Snellen was 20/95 on ETDRS (>3 lines difference), and 20/30 on Snellen was 20/25 on ETDRS (<1 line difference).
Our results show poor agreement between the Snellen and ETDRS charts, and it was more pronounced in the group with poor vision. The ETDRS measurements yielded better VA, particularly in participants with vision <20/200 (representing more advanced AMD patients). We suggest taking these findings into consideration when comparing outcomes in clinical practices (which typically measure VA using standard Snellen charts) with outcomes from clinical trials (which typically measure VA using ETDRS charts).
Ophthalmology 02/2008; 115(2):319-23. · 5.45 Impact Factor
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ABSTRACT: PURPOSE: To describe a clinical appearance of macular edema secondary to extrafoveal retinal hole using coronal (en-face) optical coherence tomography/scanning laser ophthalmoscopy (OCT/SLO) imaging. METHOD: Case report. RESULTS: A 76-year-old man developed an extrafoveal retinal hole in his right eye after pars plana vitrectomy and epiretinal membrane removal 1 year after surgery. He complained of decreased central vision. Coronal scan showed extrafoveal retinal hole with multiple retinal cysts surrounding the retinal hole and communicating with the macular area. CONCLUSION: The OCT/SLO ophthalmoscope can be useful in understanding pathophysiology of macular edema.
Retin Cases Brief Rep 01/2008; 2(2):91-93.
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ABSTRACT: To test the following hypotheses: (1) eyes from individuals with human immunodeficiency virus (HIV) have electrophysiologic abnormalities that manifest as multifocal electroretinogram (mfERG) abnormalities; (2) the retinal effects of HIV in immune-competent HIV individuals differ from the effects in immune-incompetent HIV individuals; (3) strong machine learning classifiers (MLCs), like support vector machine (SVM), can learn to use mfERG abnormalities in the second-order kernel (SOK) to distinguish HIV from normal eyes; and (4) the mfERG abnormalities fall into patterns that can be discerned by MLCs. We applied a supervised MLC, SVM, to determine if mfERGs in eyes from patients with HIV differ from mfERGs in HIV-negative controls.
Ninety-nine HIV-positive patients without visible retinopathy were divided into 2 groups: (1) 59 high-CD4 individuals (H, 104 eyes), 48.5 +/- 7.7 years, whose CD4 counts were never observed below 100, and (2) 40 low-CD4 individuals (L, 61 eyes), 46.2 +/- 5.6 years, whose CD4 counts were below 100 for at least 6 months. The normal group (N, 82 eyes) had 41 age-matched HIV-negative individuals, 46.8 +/- 6.2 years. The amplitude and latency of the first positive curve (P1, hereafter referred to as a) and the first negative curve (N1, referred to as b) in the SOK of 103 hexagon patterns of the central 28 degrees of the retina were recorded from the eyes in each group. SVM was trained and tested with cross-validation to distinguish H from N and L from N. SOK was chosen as a presumed detector of inner retinal abnormalities. Classifier performance was measured with the area under the receiver operating characteristic (AUROC) curve to permit comparison of MLCs. Improvement in performance and identification of subsets of the most important features were sought with feature selection by backward elimination.
In general, the SOK b-parameters separated L from N and H from N better than a-parameters, and latency separated L from N and H from N better than amplitude. In the HIV groups, on average, amplitude was diminished and latency was extended. The parameter that most consistently separated L from N and H from N was b-latency. With b-latency, SVM learned to distinguish L from N (AUROC = 0.7.30 +/- 0.044, P = .001 against chance [0.500 +/- 0.051]) and H from N (0.732 +/- 0.038, P = .0001 against chance) equally well. With best-performing subsets (21 out of 103 hexagons) derived by backward elimination, SVM distinguished L from N (0.869 +/- 0.030, P < .00005 against chance) and H from N (0.859 +/- 0.029, P <.00005 against chance) better than SVM with the full set of hexagons. Mapping the top 10 hexagon locations for L vs N and H vs N produced no apparent pattern.
This study confirms that mfERG SOK abnormalities develop in the retina of HIV-positive individuals. The new finding of equal severity of b-latency abnormalities in the low- and high-CD4 groups indicates that good immune status under highly active antiretroviral therapy may not protect against retinal damage and, by extension, damage elsewhere. SOKs are difficult for human experts to interpret. Machine learning classifiers, such as SVM, learn from the data without human intervention, reducing the need to rely on human skills to interpret this test.
Transactions of the American Ophthalmological Society 01/2008; 106:196-204; discussion 204-5.
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Investigative Ophthalmology & Visual Science 12/2007; 48(11):4861-3. · 3.60 Impact Factor
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ABSTRACT: The aim of this study was to investigate intraocular properties and determine the highest nontoxic dose of hexadecyloxypropyl-cyclic-HPMPA (HDP-cHPMPA), a novel, potent, intravitreally injectable, slow-releasing crystalline drug for long-acting treatment of cytomegalovirus (CMV) retinitis.
Various concentrations of HDP-cHPMPA were first studied in vitro in a human foreskin fibroblast (HFF) cell line infected with human cytomegalovirus (HCMV) to determine the EC50. In vivo, 9 pigmented rabbits and 3 doses (55, 100, and 550 microg/eye) were tested in triplicate in 1 eye of each animal. The eyes were monitored with slit lamp, tonopen, indirect ophthalmoscopy, electroretinography (ERG), and histology. A confirmation toxicity study with the dose equivalent to the highest nontoxic dose in rabbit was performed in 9 guinea pig eyes (a second species) to study the potential adverse effect on intraocular pressure (IOP).
In vitro testing in HFF cells showed an EC50 against HCMV of 0.02 microM, which is 75- and 60-fold greater than that of ganciclovir and cidofovir, respectively. All eyes injected with 550 microg/eye and 1 eye injected with 100 microg/eye of HDP-cHPMPA showed toxicity clinically (e.g., vitreous cells, disc edema, and retinal inflammation) as well as histologically (e.g., inflammatory cells in iris, vitreous, and retinal layers with disorganization). None of the eyes injected with 55 microg/eye of HDP-cHPMPA showed toxicity clinically (including ERG) and histologically. The equivalent dose (9.2 microg/eye) in the guinea pig eyes did not show toxicity either, including IOP evaluation (P > 0.05 at all time points after injection).
Intravitreal injection of the highest nontoxic dose of 55 microg/eye of HDP-cHPMPA in rabbit eyes yields a calculated intravitreal concentration of 65 microM, which is 3250-fold greater than the EC50 against HCMV (0.02 microM). Also, it does not cause hypotony in rabbit and guinea pig eyes and has a vitreous residence time of over 4 months.
Journal of Ocular Pharmacology and Therapeutics 11/2007; 23(5):433-44. · 1.51 Impact Factor
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ABSTRACT: To determine changes and need to monitor intraocular pressure (IOP) following intravitreal injection of bevacizumab (Avastin).
Seventy patients (122 injections) underwent an intravitreal injection of Avastin for exudative age-related macular degeneration treatment. Forty-one eyes (59%) had single injection, 29 eyes (41%) had repeated injections. IOP was measured before and after Avastin injection at 3, 10, and 15 minutes. Twenty-nine eyes were evaluated for baseline IOP changes after multiple injections. Statistical analysis was performed.
Baseline mean IOP was 15.17 +/- 3.42 mm Hg, with range from 08 mm Hg to 23 mm Hg. Postinjection 3 minutes the IOP had risen to a mean of 36.27 +/- 5.1 mm Hg and fell spontaneously to a mean of 24.56 +/- 5.9 mm Hg at 10 minutes. Ten eyes (14%) needed 15 minutes to drop below 30 mm Hg. All eyes were below 30 mm Hg at 15 minutes. No significant change between multiple baseline IOP measurements was detected.
Avastin injections caused a predictable probably volume-related rise in IOP which never occluded the central retinal artery and which spontaneously fell to below 30 mm Hg in all eyes within 15 minutes. This strong safety profile provides guidelines on monitoring IOP after Avastin injections. There was no IOP change after multiple injections.
Retina 11/2007; 27(8):1044-7. · 2.81 Impact Factor
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ABSTRACT: The aim of this paper was to present the results of subretinal delivery of triamcinolone acetonide (TCA) in humans with choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD).
Twenty two (22) eyes of 22 patients underwent pars plana vitrectomy with subretinal TCA administration. Two milligrams (2 mg) of preservative-free TCA were delivered through a 32-gauge automatic subretinal injector in 20 microL of volume. Visual acuity, fluorescein angiography (FA), and intraocular pressure (IOP) were recorded and compared pre- and postoperatively.
Preoperative average+/-standard deviation visual acuity in the treated eye was 1.408+/-0.129 (logMAR; median 20/400) and 1.403+/-0.114 (logMAR; median 20/300) postoperatively (P=0.51). The mean area of pre- and postoperative FA leakage in the operated eyes was 21.31+/-1.125 and 19.29+/-1.108 mm2, respectively (P=0.04). The average IOP value before treatment was 15.3+/-0.78 mmHg. Three (3) months after surgery, it was 20.5+/-2.04 mmHg (P=0.02). Six (6) months and 1 year after surgery, the average IOP was 17.0+/-0.66 mmHg (P=0.9) and 15.6+/-1.02 mmHg (P=0.6), respectively.
Subretinal TCA stabilizes visual acuity, decreases FA leakage in eyes with CNV owing to AMD, and does not increase IOP, as seen with intravitreous injections.
Journal of Ocular Pharmacology and Therapeutics 03/2007; 23(1):46-53. · 1.51 Impact Factor
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ABSTRACT: To characterize retinal changes in areas of cotton wool spots (CWSs) using optical coherence tomography (OCT) and to determine the optical density changes of the retina after CWSs have disappeared clinically.
Prospective, noninterventional, observational study.
Thirty-one patients with CWSs who underwent imaging studies.
The study groups included patients with CWSs resulting from diabetic retinopathy (n = 12), human immunodeficiency virus (HIV) retinopathy (n = 10), hypertensive retinopathy (n = 3), branch retinal vein occlusion (n = 3), uveitis (n = 2), and radiation retinopathy (n = 1). The single line scan mode of the StratusOCT Model 3000 (Carl Zeiss Meditec, Dublin, CA) was used for imaging of acute CWSs, CWSs 3 months after their resolution, and adjacent normal retina. A fundus photograph served as a template for localization of OCT scanning of CWSs. Retinal tissue reflectivity images were compared across lesion types and time. Additional imaging in 14 patients was performed to localize lesions better and to provide coronal OCT sections using the combined OCT and scanning laser ophthalmoscope.
Changes in retinal reflectivity in areas of normal retina and retina with acute and resolved CWSs.
The average reflectivity of normal retina was 58.4+/-2.1 dB, the average reflectivity in the area of active CWSs was 62.6+/-2.5 dB, and the average reflectivity in the same area after CWSs resolved was 61.0+/-2.4 dB. A significant difference (P<0.05) exists between reflectivity of normal retina and acute CWSs as well as normal retina and resolved CWSs.
Acute CWSs show a hyperreflective pattern on OCT. As they become ophthalmoscopically invisible, the OCT still shows signs of hyperreflectivity in the areas of previous CWSs (hyperreflective sign). The authors observed the same phenomenon using 2 imaging machines.
Ophthalmology 03/2007; 114(3):537-43. · 5.45 Impact Factor
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ABSTRACT: To evaluate the use of intravitreal triamcinolone (IVTA) for the treatment of macular edema secondary to immune recovery uveitis (IRU) in patients with AIDS.
Prospective, consecutive, interventional case series.
Eight eyes of 7 patients receiving 13 injections.
Prospective, consecutive, interventional case series of 13 injections involving 8 eyes in 7 patients who underwent an intravitreal injection of 20 mg decanted triamcinolone acetate for fluorescein angiographically proven IRU-related macular edema.
The primary outcome measure was vision (using the Early Treatment Diabetic Retinopathy Study chart). Other outcome measures included fluorescein angiography and optical coherence tomography.
Visual acuity improved at all time points and was statistically significant at the 1-month and 3-month follow-up examinations. The average visual improvement was 3 lines at 3 months. Retinal volume and thickness improvement were statistically significant at all time points. All patients had a minimum follow-up of 9 months, and there were no cases of cytomegalovirus reactivation.
Previous studies showed that treatment with sub-Tenon repository steroids for the treatment of macular edema of IRU was only marginally effective. However, the current study shows that IVTA can be an effective short-term treatment for macular edema secondary to IRU in patients with AIDS. Longer follow-up is needed to assess the durability of the effect and to monitor for longer-term complications and outcomes.
Ophthalmology 03/2007; 114(2):334-9. · 5.45 Impact Factor
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ABSTRACT: To test the following hypotheses: (1) eyes from patients with human immunodeficiency virus (HIV) have retinal damage that causes subtle field defects, (2) sensitive machine learning classifiers (MLCs) can use these field defects to distinguish fields in HIV patients and normal subjects, and (3) the subtle field defects form meaningful patterns. We have applied supervised MLCs--support vector machine (SVM) and relevance vector machine (RVM)--to determine if visual fields in patients with HIV differ from normal visual fields in HIV-negative controls.
HIV-positive patients without visible retinopathy were divided into 2 groups: (1) 38 high-CD4 (H), 48.5 +/- 8.5 years, whose CD4 counts were never below 100; and (2) 35 low-CD4 (L), 46.1 +/- 8.5 years, whose CD4 counts were below 100 at least 6 months. The normal group (N) had 52 age-matched HIV-negative individuals, 46.3 +/- 7.8 years. Standard automated perimetry (SAP) with the 24-2 program was recorded from one eye per individual per group. SVM and RVM were trained and tested with cross-validation to distinguish H from N and L from N. Area under the receiver operating characteristic (AUROC) curve permitted comparison of performance of MLCs. Improvement in performance and identification of subsets of the most important features were sought with feature selection by backward elimination.
SVM and RVM distinguished L from N (L: AUROC = 0.804, N: 0.500, P = .0002 with SVM and L: .800, P = .0002 with RVM) and H from N (H: 0.683, P = .022 with SVM and H: 0.670, P = .038 with RVM). With best-performing subsets derived by backward elimination, SVM and RVM each distinguished L from N (L: 0.843, P < .00005 with SVM and L: 0.870, P < .00005 with RVM) and H from N (H: 0.695, P = .015 with SVM and H: 0.726, P = .007 with RVM). The most important field locations in low-CD4 individuals were mostly superior near the blind spot. The location of important field locations was uncertain in high-CD4 eyes.
This study has confirmed that low-CD4 eyes have visual field defects and retinal damage. Ranking located important field locations superiorly near the blind spot, implying damage to the retina inferiorly near the optic disc. Though most fields appear normal in high-CD4 eyes, SVM and RVM were sufficiently sensitive to distinguish these eyes from normal eyes with SAP. The location of these defects is not yet defined. These results also validate the use of sensitive MLC techniques to uncover test differences not discernible by human experts.
Transactions of the American Ophthalmological Society 01/2007; 105:111-8; discussion 119-20.
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Retinal Cases & Brief Reports 12/2006; 1(1):52-53.
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Retina 11/2006; 26(8):853-8. · 2.81 Impact Factor
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ABSTRACT: The aim of this study was to investigate the extent if recombinant human hyaluronidase (rhuPH20) can enhance trans-scleral penetration of sub-Tenon's dexamethasone (DM) into the posterior segment of the eye.
rhuPH20 was purified from conditioned media through a series of ion exchange, hydrophobic interaction, aminophenylboronate, and hydroxyapatite chromatography to greater than 90% purity based upon specific activity. Only the right eye of each rabbit was injected. The first group (n = 16) received an injection of DM and rhuPH20, whereas the second group (n = 16) received DM only. The eyes were enucleated 1, 2, 3, and 6 h after the injection, and the choroid, retina, vitreous, aqueous, and serum were harvested. DM concentration was assessed by mass spectrometry. Histology (n = 2) and immunohistochemistry (n = 2) was performed to detect toxicity and the presence of the rHuPH20, respectively.
We observed no histopathologic damage to ocular tissues after sub-Tenon's injection. This enzyme significantly increased DM level in the choroid and the retina 3 h after administration. The rise in levels was transient returning to normal levels by 6 h.
Sub-Tenon's coinjection of rHuPH20 with DM resulted in a general increase in DM levels in ocular tissues and the serum, with significant increase in the choroid and the retina, 3 h after administration.
Journal of Ocular Pharmacology and Therapeutics 11/2006; 22(5):362-9. · 1.51 Impact Factor
