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Biomedical subjects

Anat Loewenstein

Publications and source records attributed to Anat Loewenstein.

At least 19 recordsLinked to original sources

Electrophysiologic and retinal penetration studies following intravitreal injection of bevacizumab (Avastin).

PURPOSE: Intravitreal bevacizumab (Avastin; Genentech Inc., San Francisco, CA) is a new treatment for age-related macular degeneration. The aim of this study was to evaluate retinal penetration and toxicity of bevacizumab. METHODS: Ten albino rabbits were injected intravitreally with 0.1 mL (2.5 mg) of Avastin into one eye and 0.1 mL saline into the fellow eye. The electroretinogram (ERG) was recorded after 3 hours, 3 days, and 1, 2, and 4 weeks. The visual evoked potential (VEP) was recorded after 4 weeks. Confocal immunohistochemistry was used to assess retinal penetration. RESULTS: The ERG responses of the control and experimental eyes were similar in amplitude and pattern throughout the follow-up period. The flash VEP responses of the experimental eyes were of normal pattern and amplitude and did not differ from those recorded by stimulation of the control eye alone. Full thickness retinal penetration was present at 24 hours and was essentially absent at 4 weeks. CONCLUSIONS: Bevacizumab was found to be nontoxic to the retina of rabbits based on electrophysiologic studies. Full thickness retinal penetration may explain observed clinical effects of intravitreal bevacizumab. Although it is difficult to directly extrapolate to humans, our study supports the safe use of intravitreal bevacizumab injection.

Animals↗

Retinal toxicity of indocyanine green in albino rabbits.

PURPOSE: Intravitreal indocyanine green (ICG) is commonly used in vitreoretinal surgery. The purpose of this study was to evaluate possible toxicity of ICG in the retina of albino rabbits. METHODS: Twenty-two albino rabbits were injected intravitreally with 0.1 mL ICG solution in one eye, and three rabbits were studied for the effects of 0.1 mL distilled water. All rabbits were injected intravitreally with 0.1 mL saline into the fellow eye, which served as the control. The electroretinogram (ERG) and visual evoked potential (VEP) were recorded from each rabbit at different time intervals after injection. The rabbits were killed at the termination of the follow-up periods and their retinas prepared for histologic examination at the light microscopic level. RESULTS: Three hours after injection, the ERG responses were reduced in amplitude in all ICG-injected eyes, and the VEPs were of abnormal pattern (reduced amplitude and delayed). Partial dose-dependent recovery was observed during 4 weeks of follow-up. Light microscopy of the retinas of the experimental eyes exhibited considerable damage to all retinal layers in all eyes studied that received the highest ICG dose. CONCLUSIONS: ICG is potentially toxic to all retinal layers of the albino rabbit. Although it is difficult to extrapolate these findings directly to human eyes, caution should be exercised when using ICG intravitreally.

Animals↗

Intravitreal triamcinolone injection for diffuse diabetic macular edema with foveal cystoid changes.

BACKGROUND: Diabetic macular edema causes visual loss in almost one-third of diabetic patients. There is currently no treatment for the accompanying cystoid foveal changes. OBJECTIVES: To assess the clinical outcome, i.e., change in visual acuity, in patients treated with steroids for long-standing diabetic macular edema with foveal cystoid changes. METHODS: In the ophthalmology department of a tertiary care university-affiliated medical center and the ophthalmology service of a health management organization, 46 diabetic subjects (56 eyes) who had diabetic macular edema with cystoid foveal changes received one intravitreal injection of 4 mg triamcinolone acetonide. RESULTS: The mean baseline (pre-injection) visual acuity of 0.21 increased to 0.31 and 0.48 at 1 and 3 months, respectively, after which it decreased to 0.33 at 6 months. The mean intraocular pressure was 15.07 mmHg at baseline, 15.83 at day 1, gradually rising to 17.16, 18.38 and 18.57 mmHg at 1, 3 and 6 months respectively. Three patients suffered immediate visual decline after the injection. CONCLUSIONS: Intravitreal triamcinolone acetonide may be a therapeutic option for long-standing diabetic macular edema with foveal cystoid changes.

Aged↗

Endogenous Phialemonium curvatum endophthalmitis.

PURPOSE: To report a case of bilateral endogenous Phialemonium curvatum endophthalmitis, secondary to intrapenile injections for erectile dysfunction. DESIGN: Observational case report. METHODS: A 71-year-old man with P. curvatum endocarditis and bilateral decreased vision was diagnosed as having bilateral endogenous endophthalmitis. P. curvatum was identified in cultures that were performed on samples of the vitreous. Treatment consisted of bilateral vitrectomy and intraocular and systemic antifungals. RESULTS: Despite resolution of the systemic infection, the patient's postoperative visual acuity remained limited to hand movement, and the ophthalmic clinical picture remained unchanged. CONCLUSIONS: P. curvatum is a pathogen that can be readily isolated from the vitreous. The authors are unaware of previous reported cases of ocular infection that was caused by P. curvatum.

Aged↗

Preferential Hyperacuity Perimeter (PreView PHP) for detecting choroidal neovascularization study.

PURPOSE: To assess the ability of the Preferential Hyperacuity Perimeter (PreView PHP; Carl Zeiss Meditec, Dublin, CA) to detect recent-onset choroidal neovascularization (CNV) resulting from age-related macular degeneration (AMD) and to differentiate it from an intermediate stage of AMD. DESIGN: Prospective, comparative, concurrent, nonrandomized, multicenter study. PARTICIPANTS: Eligible participants' study eyes had a corrected visual acuity of 20/160 or better and either untreated CNV from AMD diagnosed within the last 60 days or an intermediate stage of AMD. METHODS: After obtaining consent, visual acuity with habitual correction, masked PHP testing, stereoscopic color fundus photography, and fluorescein angiography were performed. Photographs and angiograms were evaluated by graders masked to diagnosis and PHP results. The reading center's diagnosis determined if the patient was categorized as having intermediate AMD or neovascular AMD. MAIN OUTCOME MEASURES: A successful study outcome was defined a priori as a sensitivity of at least 80% and a specificity of at least 80%. RESULTS: Of 185 patients who gave consent to be enrolled, 11 (6%) had PHP results judged to be unreliable. An additional 52 were not included because they did not meet all eligibility criteria. Of the remaining 122 patients, 57 had an intermediate stage of AMD and 65 had neovascular AMD. The sensitivity to detect newly diagnosed CNV using PHP testing was 82% (95% confidence interval [CI], 70%-90%). The specificity to differentiate newly diagnosed CNV from the intermediate stage of AMD using PHP testing was 88% (95% CI, 76%-95%). CONCLUSIONS: Preferential Hyperacuity Perimeter testing can detect recent-onset CNV resulting from AMD and can differentiate it from an intermediate stage of AMD with high sensitivity and specificity. These data suggest that monitoring with PHP should detect most cases of CNV of recent onset with few false-positive results at a stage when treatment usually would be beneficial. Thus, this monitoring should be considered in the management of the intermediate stage of AMD.

Aged↗

Red blood cell membrane mechanical fluctuations in non-proliferative and proliferate diabetic retinopathy.

PURPOSE: To study whether cell membrane mechanical fluctuation (CMF) of red blood cells (RBCs) are attenuated in non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). PATIENTS AND METHODS: Point dark-field microscopy-based recordings of local membrane displacements (frequency 0.3-25 Hz) were compared between type 2 diabetes patients with mild-to-moderate and severe NPDR and type 2 diabetes patients with PDR. The matched control group, corresponding to each stage of diabetic retinopathy, was based on non-diabetic patients who were evaluated in our clinic due to cataract. RESULTS: The average mean values of the maximal CMF amplitude did not differ between RBCs of NPDR patients (n=20) and controls (n=20) (19.5+/-1.5% and 19.6+/-1.7%, respectively). A statistically significant decrease in CMF amplitudes was observed in patients with PDR compared with patients with a non-proliferative disease (NPDR -20%, PDR -90%). CONCLUSION: This new rheological characteristic demonstrates differences in the mechanical properties of RBCs in different stages of diabetic retinopathy. The significant reduction in CMF in patients with PDR may shed more light on the possible mechanism modulating retinal ischemia and leading to angiogenesis in these patients. Larger-scale studies are needed to evaluate these findings and the possible correlation between significantly lower CMF values and the progression of diabetic retinopathy.

Adenosine Triphosphatases↗

Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1).

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.

Amino Acid Sequence↗

Replacing the Amsler grid: a new method for monitoring patients with age-related macular degeneration.

PURPOSE: To investigate a method that uses hyperacuity, the Macular Computerized Psychophysical Test (MCPT), to evaluate the central macular visual field in patients with age-related macular degeneration (AMD). DESIGN: Prospective case-control study of a diagnostic test. PARTICIPANTS AND CONTROLS: One hundred eight eyes of 108 Patients with AMD and 51 eyes of 51 age-matched patients with no retinal disease. Patients with AMD included 32 (30%) patients with choroidal neovascularization (CNV), 23 (21%) with geographic atrophy (GA), 35 (32%) with AMD with high-risk characteristics (HRC), and 18 (17%) with early AMD with non-HRC. TESTING: Each subject underwent the MCPT, in which a virtual line composed of dots (white dots on a black background, maximal contrast) is flashed across different macular loci to a perifoveal radius of 7 degrees. Patients' responses were recorded and automatically analyzed using a specific algorithm developed before the onset of the study. All patients also underwent a supervised Amsler grid examination on the encounter before or after the MCPT in random order. MAIN OUTCOME MEASURES: Distortion, scotoma, or blurring perceived by the patient after a swift change of fixation was considered positive on the MCPT. Any perception of distortion, scotoma, or blurring was considered positive on the Amsler grid. RESULTS: Of the 32 patients with CNV, 30 (94%) were found positive on the MCPT and 11 (34%) were found positive on the Amsler grid. Of the 23 GA patients, 21 (91%) were found positive on the MCPT and 7 (30%) were found positive on the Amsler grid. Of the 35 HRC patients, 28 (80%) were found positive on the MCPT and 3 (9%) were found positive on the Amsler grid, and of the 18 early AMD with non-HRC patients, 8 (44%) were found positive on the MCPT and 3 (17%) were found positive on the Amsler grid. Of the 51 controls, 3 (6%) were positive on the MCPT and 1 (2%) was positive on the Amsler grid. CONCLUSIONS: The MCPT was superior to the Amsler grid in detecting AMD-related lesions in this cohort. Studies are underway to determine whether the MCPT is feasible for home monitoring to provide early detection of progression to CNV.

Aged↗

Colchicine in tear fluid of treated patients with familial Mediterranean fever.

PURPOSE: The study aimed to determine whether detectable concentrations of colchicine are present in the tear fluid of treated patients with familial Mediterranean fever (FMF) and thus demonstrate a possible route by which colchicine reaches the corneal surface. METHODS: Tear fluid samples (50-100 microL) were collected from eight FMF patients on long-term colchicine treatment. Colchicine tear fluid concentrations were determined in all patients by radioimmunoassay using goat anticolchicine antibodies and [3H]colchicine (Dupont, Wilmington, DE). RESULTS: Detectable concentrations of colchicine, with no apparent effect on the ocular surface, were found in all tear fluid samples (median, 0.46 ng/mL; range, 0.24-1.05 ng/mL). CONCLUSIONS: This study provides evidence of the route by which colchicine, given systemically, reaches the corneal surface and thus gives credence to the possible inhibitory effect of this drug on corneal wound healing in the cases described in the literature.

Adult↗

Interferon-alpha-associated bilateral simultaneous ischemic optic neuropathy.

The authors describe one patient with essential thrombocytosis and one with chronic hepatitis C infection who developed bilateral simultaneous anterior ischemic optic neuropathy within 3 months of starting treatment with interferon-alpha. One patient had several typical risk factors for conventional AION; the other did not. These cases are the fourth and fifth reported examples of this phenomenon. Interferon-alpha treatment may cause or aggravate the risk of developing anterior ischemic optic neuropathy. Vulnerable patients should be advised of this potential complication, assisted in reducing risk factors, and monitored for optic nerve and retinal vascular complications.

Adult↗

Hyperhomocystinemia in pseudoexfoliation glaucoma.

PURPOSE: To determine the prevalence of hyperhomocystinemia in patients with pseudoexfoliation glaucoma. PATIENTS AND METHODS: This prospective study included 30 patients with glaucoma and 30 age-matched controls with no history of ocular disease who were undergoing routine physical checkups. Plasma homocysteine levels of all the study participants were determined using high-performance liquid chromatography, and values exceeding 15 micromol/L were considered elevated. RESULTS: The mean plasma homocysteine level was 16.80 +/- 3.20 and 12.39 +/- 1.97 micromol/L in glaucoma patients and controls, respectively (P<0.0001). Fifteen glaucoma patients (50%) had hyperhomocystinemia compared with 3 controls (10%) (P=0.0015). CONCLUSION: Hyperhomocystinemia may be associated with pseudoexfoliation glaucoma, which may partially explain the increased risk of vascular diseases among patients with pseudoexfoliation syndrome.

Aged↗

The effect of latanoprost on accommodation in young patients with ocular hypertension.

PURPOSE: To determine whether topical latanoprost 0.005% had an effect on accommodative capacity after 1 month of treatment in young patients with ocular hypertension. PATIENTS AND METHODS: Fifteen patients (9 men and 6 women, aged 20-40 years) with ocular hypertension were instructed to instill the drug to their right eye for 1 month; the left eye received no medication and served as control. Near point of accommodation, refraction, and intraocular pressure (IOP) were determined after 1 month of treatment. RESULTS: After 1 month of treatment with latanoprost, the mean IOP was reduced by 22.8% (5.8 mm Hg) in the treated eye and 1.86% (0.47 mm Hg) in the untreated control eye. No significant changes in refraction or near point of accommodation were observed in the treated or untreated eye. CONCLUSION: Short-term treatment with latanoprost 0.005% does not effect refraction or accommodation in young patients with ocular hypertension.

Accommodation, Ocular↗

Detachment of subfoveal choroidal neovascularization in age-related macular degeneration.

PURPOSE: To report the entity of partial detachment and folding of subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (ARMD). DESIGN: Interventional case reports. METHODS: Review of the features of CNV detachment in two patients with CNV due to ARMD by contact lens slit-lamp biomicroscopy, fluorescein angiography, optical coherence tomography, and three-dimensional confocal scanning laser indocyanine green (ICG) angiography. RESULTS: One patient out of approximately 300 (0.5%) ARMD patients treated by photodynamic therapy (PDT) developed partial CNV detachment and folding 6 weeks after the second PDT treatment. Another patient out of approximately 100 (1.0%) ARMD patients treated by transpupillary thermotherapy (TTT) developed partial CNV detachment and folding 6 weeks after the second TTT treatment. The CNVs were large (2,500 microm to 4,500 microm) and located between the retina and the retinal pigment epithelium. In each, these findings were clearly visualized by slit-lamp biomicroscopy. Fluorescein angiography demonstrated an associated retinal pigment epithelium tear in one patient. Optical coherence tomography showed distinctive features and confocal scanning laser ICG further delineated the detached folded CNV. The best-corrected visual acuity improved in one patient from 20/80 to 20/40 and in the other from counting fingers at 6 feet to 20/200 after the CNV detachment. CONCLUSIONS: Partial CNV detachment and folding represent a unique, not previously reported, and possibly favorable outcome of PDT and TTT. The low energy and selectivity of these treatments may explain this phenomenon.

Aged↗

Induced sputum for identifying sarcoidosis in patients with uveitis.

OBJECTIVE: To evaluate the value of the induced sputum technique in diagnosing sarcoidosis as the cause of uveitis. DESIGN: Comparative case series. PARTICIPANTS: Seventeen patients with uveitis. Two control groups were used. The first included 10 patients with sarcoid without uveitis; the second included 5 healthy volunteers. TESTING: Sputum was induced by a 20-minute inhalation of 3.5% saline using an ultrasonic nebulizer. Samples were studied by differential counts of 200 cells on cytopreps stained by Giemsa. T lymphocyte subset analyses were done by fluorescence-activated cell sorter using the monoclonal antibodies CD4 (T helper cells) and CD8 (T suppressor-cytotoxic cells). Angiotensin-converting enzyme (ACE) serum levels were obtained. MAIN OUTCOME MEASURES: A CD4/CD8 ratio >2.5 and an ACE level >145 microl/ml/minute were considered to be abnormal. RESULTS: The difference in the CD4/CD8 ratios in the induced sputum examination between the group of patients with an elevated ACE level and the group of patients with an ACE level within normal limits was statistically significant (P = 0.0001). CONCLUSIONS: The induced sputum examination showed increased CD4/CD8 ratios in patients with uveitis who also had elevated ACE levels, suggesting the presence of sarcoidosis.

Adult↗

The usefulness of an inflammation meter to detect the presence of infection/inflammation in elderly patients.

BACKGROUND: Medical personnel who work in small geriatric institutions most frequently do not have access to realtime laboratory facilities. METHODS: In order to present a new method to determine the presence of an inflammatory response and for the assessment of its intensity, 118 patients aged 77 +/- 6 years with various bacterial infections were evaluated as well as 129 elderly individuals with various stressful conditions but no acute infections who served as controls. The leukocyte and erythrocyte adhesiveness/aggregation tests were performed by using a simple slide test and image analysis. The availability of the CD11b/CD18 and CD62L antigen on the leukocytes' surface was measured by whole blood flow cytometry, and the quantitative C-reactive protein by using laser nephelometry and specific antihuman C-reactive protein antibodies. RESULTS: A significant difference was noted between patients and controls for all variables obtained by the slide test and image analysis. In addition, a highly significant correlation was noted between the number of leukocytes counted on the slides and white blood cell count, between the leukocyte adhesiveness/aggregation test and quantitative C-reactive protein, and between the degree of erythrocyte adhesiveness/aggregation and either the Westergren sedimentation or fibrinogen concentration. CONCLUSIONS: By using our low-cost and real-time slide test, any medical or paramedical personnel can get relevant information regarding the presence of an acute phase response at the point of care.

Age Factors↗

Excision of pterygium and conjunctival autograft.

BACKGROUND: Pterygium is a common disease in Israel. Different surgical techniques are used to manage it with varying degrees of success. OBJECTIVES: To evaluate the efficacy and safety of a conjunctival autograft after excision of pterygium. METHODS: Excision followed by conjunctival autograft was used to treat 40 eyes of 40 patients with pterygium. The surgical results were evaluated retrospectively. Follow-up continued for a median of 296 days (range 6-1,056); 26 cases were followed for more than 100 days (average 418 days) and comprised the study cohort. All reported procedures were performed consequentially and by one surgeon in the Tel Aviv Sourasky Medical Center, Israel between 1 June 1997 and 31 March 2000. RESULTS: There were two recurrences of pterygium (2/26, 7.7%) 2 months postoperatively. There were no major complications. Superficial comeal vessels (without concurrent fibrosis) appeared in 10 of 17 cases sutured with nylon, but none occurred in any of the seven grafts sutured with vicryl (P = 0.068). The average LogMAR-corrected visual acuity of the study group improved slightly, from 6/16.5 to 6/11 (P = 0.003). CONCLUSIONS: Excision of pterygium with a conjunctival autograft is a safe and effective operation, with no procedure-specific added surgical risks. The relatively long surgical time and microsurgical methods required to perform the procedure properly have hindered its acceptance as the mainstream approach to pterygium management. Long-term follow-up is needed for better discernment of the surgical results in Israel.

Adult↗