Macular Degeneration: Loewenstein A

Waisbourd M, Leibovitch I, Loewenstein A, Yassur Y. · No affiliation provided · Harefuah. · Pubmed #18814519 No free full text.

Abstract: Age-related macular degeneration is the leading cause of blindness and visual impairment in the developed world. The recently introduced anti-vascular endothelial growth factor (VEGF) intravitreal injections of Ranibizumab (Lucentis) and Bevacizumab (Avastin) generated a heated academic argument: on the one hand Lucentis is the only drug that was proven effective and relatively safe in large prospective double-blinded studies, albeit this drug is expensive and might cost up to $1000 per single injection. On the other hand, Avastin is widely used worldwide as a low cost alternative for Lucentis, with an estimated cost of about $120 per injection, although its efficacy and side effects were investigated only in smaller retrospective studies. The ophthalmic community still lacks definite information regarding which is the preferred drug, and awaits the results of a large prospective study comparing the two drugs.

Waisbourd M, Loewenstein A. · No affiliation provided · Isr Med Assoc J. · Pubmed #17939632 links to  free full text

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Loewenstein A, Goldstein M. · No affiliation provided · Isr Med Assoc J. · Pubmed #16833175 links to  free full text

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Loewenstein A, Anonymous00137. · Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Israel. · Retina. · Pubmed #17891011 No free full text.

Abstract: BACKGROUND: The main cause for visual loss in age-related macular degeneration (AMD) is the development of choroidal neovascularization (CNV), which has been shown to occur in 18% of patients over 5 years. Even though satisfactory treatments for CNV are available, in the majority of cases no improvement in visual acuity occurs and in those it does it is mostly limited. Early detection has the potential of significantly improving the final visual outcome of patients who develop subfoveal CNV. METHODS: This review is a summary of the importance of early detection in the management of AMD, in view of the current available treatment methods. It is a review of the results of early detection of AMD using the Preferential Hyperacuity Perimeter (PHP). RESULTS: Awareness for symptoms, use of the Amsler grid and monitoring by an ophthalmologist are not satisfactory means for early detection of AMD. The PHP has good sensitivity and specificity in detecting CNV patient early and differentiate them from intermediate AMD. CONCLUSION: In an era of excellent treatments available for CNV treatment, early detection of CNV by novel technology modalities such as the PHP at a frequency that allows early detection (approximately 4 times a year) is crucial in the armamentarium of AMD patient management.

Waisbourd M, Loewenstein A, Goldstein M, Leibovitch I. · Ophthalmology Department, Tel-Aviv Sourasky Medical Centre, Tel-Aviv University, Tel-Aviv, Israel. · Drugs Aging. · Pubmed #17702534 No free full text.

Abstract: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the industrialised world. While treatment options for advanced AMD have been rather limited until recently, the introduction of intravitreal injections of anti-angiogenic agents appears to be a promising and revolutionary mode of treatment for this blinding disease. Vascular endothelial growth factor (VEGF) appears to play a pivotal role in the pathogenesis of choroidal neovascularisation, one of the cornerstones of advanced AMD. Pegaptanib, the first anti-VEGF treatment approved for AMD patients, is a VEGF-neutralising aptamer that specifically inhibits one isoform of VEGF (VEGF-165). Although evidence suggested that pegaptanib was superior to previous treatment options, results with this agent were still unsatisfactory. Ranibizumab is a humanised anti-VEGF monoclonal antibody fragment that inhibits all isotypes of VEGF. This new drug has demonstrated a high efficacy profile in terms of inhibiting disease progression and even improving visual acuity. Bevacizumab is a full-length anti-VEGF antibody that was originally approved for use in metastatic colon cancer and is under investigation as a low-cost off-label alternative for patients with AMD. There is growing evidence that this drug may be an effective and safe alternative to the more expensive ranibizumab, although prospective multicentre trials are required to fully investigate this issue. Undoubtedly, the concept of directly injecting anti-VEGF drugs into the vitreal cavity brings new hope to many AMD patients.

Zayit-Soudry S, Moroz I, Loewenstein A. · Department of Ophthalmology, Tel-Aviv Sourasky Medical Center, Tel-Aviv University, Tel-Aviv, Israel. · Surv Ophthalmol. · Pubmed #17472800 No free full text.

Abstract: Detachment of the retinal pigment epithelium is a prominent feature of many chorio-retinal disease processes, the most prevalent of which is age-related macular degeneration (AMD). Detachment of the retinal pigment epithelium may or may not be associated with choroidal neovascularization and may be caused by different types of pathogenesis, each associated with distinct angiographic features, natural course, visual prognosis, and response to treatment. The phrase "detachment of the retinal pigment epithelium" is used quite often, not always in the correct association and with no clear differentiation between its various types. It is important to identify the specific nature of detachment of the retinal pigment epithelium, and to establish an accurate diagnosis and treatment plan. Therefore, we present a review of the existing types of detachment of the retinal pigment epithelium with what we propose as being appropriate nomenclature and classification, and potential treatment recommendations.

Yassur Y, Weinberger D, Goldstein M, Loewenstein A. · No affiliation provided · Harefuah. · Pubmed #11062957 No free full text.

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Goldstein M, Loewenstein A, Barak A, Pollack A, Bukelman A, Katz H, Springer A, Schachat AP, Bressler NM, Bressler SB, Cooney MJ, Alster Y, Rafaeli O, Malach R, Anonymous00107. · Department of Ophthalmology, Tel-Aviv Medical Center, Israel. · Retina. · Pubmed #15805906 No free full text.

Abstract: PURPOSE: To compare the preferential hyperacuity perimeter (PHP) with an Amsler grid in detection of age-related macular degeneration (AMD). METHODS: Patients underwent refraction, visual acuity examination, PHP, Amsler grid examination, and macular photography. RESULTS: One hundred fifty patients participated in the trial. Of 19 eyes with neovascular AMD, 19 (100%) were positive on the PHP, and 10 (53%), on the Amsler grid. Of 27 eyes with geographic atrophy, 26 (96%) were positive on the PHP, and 12 (44%), on the Amsler grid. Of 20 eyes with intermediate AMD, 14 (70%) were positive on the PHP, and 4 (20%), on the Amsler grid. Of 51 eyes with early AMD, 21 (41%) were positive on the PHP, and 4 (8%), on the Amsler grid. Of 33 eyes with no AMD, 6 (18%) were positive on the PHP, and none, on the Amsler grid. Thus, 80 (68%) of 117 patients with AMD had a positive PHP, while 30 (26%) had positive results of Amsler grid examination (P < 0.001, McNemar test). CONCLUSION: The PHP had greater sensitivity, although with a relatively high rate of false-positive results for healthy individuals, than the Amsler grid in detecting AMD-related lesions.

Zur D, Ben Simon GJ, Loewenstein A, Alster Y, Moisseiev J, Ullman S. · Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel. · Ophthalmic Surg Lasers Imaging. · Pubmed #15497550 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: To examine a new high-resolution kinetic mapping method for scotoma in age-related macular degeneration. PATIENTS AND METHODS: A computer-based program for kinetic visual field mapping was tested in 10 healthy subjects and 14 patients with age-related macular degeneration and fixed preferred retinal locus. The stimulus was presented using a back projector on a screen located 40 cm from the subject. The findings were then compared with static results. RESULTS: Control group mapping revealed good congruency with the anatomic blind spot. Mapping of the 14 patients with age-related macular degeneration was rapid and revealed good accuracy. The average deviation of the mapping border from the anatomic scotoma border was no more than 3.1% of the scotoma radius. Static mapping of 7 of the patients with age-related macular degeneration was longer and revealed lower accuracy. CONCLUSIONS: The proposed method is more rapid, accurate, and consistent than static mapping. It allows accurate mapping of central scotoma with suprathreshold stimulus, and may be used in the future for detecting the early stages of age-related macular degeneration using subthreshold stimulus.

Loewenstein A, Malach R, Goldstein M, Leibovitch I, Barak A, Baruch E, Alster Y, Rafaeli O, Avni I, Yassur Y. · Department of Ophthalmology, Tel-Aviv Medical Center, Tel-Aviv, Israel. · Ophthalmology. · Pubmed #12750099 No free full text.

Abstract: 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.

Zayit-Soudry S, Alfasi M, Goldstein M, Moisseiev J, Axer-Siegel R, Pollack A, Yassur Y, Loewenstein A. · Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. · Retina. · Pubmed #17621192 No free full text.

Abstract: PURPOSE: To determine the rate of agreement among five retina specialists in classifying various angiographic features of subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD), as evaluated on printed digital fluorescein angiogram (FA) frames, as well as determination of eligibility for photodynamic treatment (PDT) according to established guidelines. METHODS: Ninety-two digital FAs demonstrating subfoveal CNV secondary to AMD were evaluated independently by five retina specialists. The pattern of classic component could be classified as no classic component, minimally classic, predominantly classic, or classic only. Each grader was asked to determine eligibility of each case to PDT according to established treatment guidelines, national health insurance guidelines, and one's own personal judgment. RESULTS: The kappa coefficient of concordance calculated for all five observers regarding CNV localization was 0.285, indicating fair overall agreement, and was 0.295, indicating fair agreement, regarding classification of leakage pattern. The kappa coefficient of agreement calculated for all five graders regarding eligibility for treatment according to established international guidelines, national health insurance, and each grader's own personal judgment was 0.163, 0.33, and 0.164, respectively, indicating slight to fair overall agreement. CONCLUSION: Considerable variability may exist among retina specialists interpreting FAs and should be considered in the assessment of treatment guidelines.

Barak A, Regenbogen M, Goldstein M, Loewenstein A. · Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. · Isr Med Assoc J. · Pubmed #16544727 links to  free full text

Abstract: 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.

Shahar J, Avery RL, Heilweil G, Barak A, Zemel E, Lewis GP, Johnson PT, Fisher SK, Perlman I, Loewenstein A. · Department of Ophthalmology, Tel-Aviv Medical Center, Israel. · Retina. · Pubmed #16508424 No free full text.

Abstract: 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.

Alster Y, Bressler NM, Bressler SB, Brimacombe JA, Crompton RM, Duh YJ, Gabel VP, Heier JS, Ip MS, Loewenstein A, Packo KH, Stur M, Toaff T, Anonymous00244. · Clin Reg Consulting Services Inc., Irvine, California, USA. · Ophthalmology. · Pubmed #16154198 No free full text.

Abstract: 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.

Goldstein M, Heilweil G, Barak A, Loewenstein A. · Department of Ophthalmolgy, Tel-Aviv Medical center, Sackler School of medicine, Tel-Aviv, Israel. · Eye. · Pubmed #15803179 No free full text.

Abstract: PURPOSE: To describe retinal pigment epithelial tear following photodynamic therapy (PDT) for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN: Retrospective interventional case series. METHODS: A retrospective study in an institutional practice. We describe seven cases of retinal pigment epithelial (RPE) tear, which developed in seven eyes of seven patients following PDT. All eyes had subfoveal CNV secondary to AMD. RESULTS: Six eyes had occult subfoveal CNV, and one eye had recurrent classic subfoveal CNV. In five patients, the eye that developed the tear was the second eye, whereas the first eye had a disciform scar. In four eyes, the RPE tear developed after one PDT, in one eye the RPE tear developed after the second PDT, and in two eyes the RPE tear developed after the third PDT. In five of seven cases, there was a significant visual deterioration following the RPE tear. CONCLUSIONS: RPE tear is a complication that may occur following PDT in particular when the PDT is applied to an occult subfoveal CNV.

Rumelt S, Kaiserman I, Rehany U, Ophir A, Pikkel J, Loewenstein A. · Department of Ophthalmology, Hadassah University Hospital, Jerusalem, Israel. · Am J Ophthalmol. · Pubmed #12470749 No free full text.

Abstract: 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.

Waisbourd M, Rabinovitch A, Heilweil G, Goldstein M, Loewenstein A. · No affiliation provided · Eye. · Pubmed #17369811 No free full text.

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