Macular Degeneration: Axer-Siegel R

Axer-Siegel R, Stiebel-Kalish H, Rosenblatt I, Strassmann E, Yassur Y, Weinberger D. · Department of Ophthalmology, Rabin Medical Center, Petah Tiqva, Israel. · Ophthalmology. · Pubmed #10485531 No free full text.

Abstract: OBJECTIVE: To determine whether the use of supplemental prophylactic vancomycin in the irrigating solution during extracapsular lens extraction is associated with increased incidence of cystoid macular edema. DESIGN: Prospective, randomized, double-masked clinical study. PARTICIPANTS: Consecutive series of 118 patients 60 years of age or older undergoing cataract surgery. INTERVENTION: The study group received an irrigating balanced salt solution supplemented with vancomycin (10 microg/ml), and the control group received the salt solution only. Fluorescein angiography was performed 1 and 4 months after surgery. MAIN OUTCOME MEASURES: Evidence of angiographic and clinical cystoid macular edema, and visual acuity at 1 and 4 months after surgery. RESULTS: The rate of postoperative angiographic cystoid macular edema was significantly higher in the study patients than in the control group at 1 month (55% vs. 19%, P = 0.0006) and 4 months (26% vs. 4%, P = 0.0099). The rates of clinical macular edema were 23% and 7%, respectively, at 1 month (P = 0.011) and 20% versus 0% at 4 months (P = 0.006). Visual acuity of 20/30 or better was noted at 4 months after surgery in 76% of the study group compared to 95.5% of the control group. CONCLUSIONS: The role of preventive intracameral vancomycin during intraocular surgery should be reassessed in view of the associated increase in the incidence of angiographic cystoid macular edema.

Chowers I, Meir T, Lederman M, Goldenberg-Cohen N, Cohen Y, Banin E, Averbukh E, Hemo I, Pollack A, Axer-Siegel R, Weinstein O, Hoh J, Zack DJ, Galbinur T. · Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. · Mol Vis. · Pubmed #19065273 links to  free full text

Abstract: PURPOSE: Single nucleotide polymorphisms (SNPs) in the tightly linked LOC387715/ARMS2 and HTRA1 genes have been associated with age-related macular degeneration (AMD). We tested whether these SNPs are associated with AMD in Israeli populations, if they underlie variable phenotype and response to therapy in neovascular AMD (NVAMD), and if HTRA1 expression in vivo is associated with its promoter variant. METHODS: Genotyping for the rs10490924 SNP in LOC387715/ARMS2 and the rs11200638 SNP in HTRA1 was performed on 255 NVAMD patients and 119 unaffected controls from Ashkenazi and Sephardic Jewish, and from Arab origins which are the main ethnic groups composing the Israeli population. Genotyping was correlated with phenotype and response to therapy among 143 patients who underwent photodynamic therapy (PDT). HTRA1 mRNA levels in white blood cells (WBCs), measured by quantitative PCR, were correlated with genotype in 27 participants. RESULTS: Both SNPs were in almost complete linkage disequilibrium (D'=0.96-1). Homozygotes for the T allele of rs10490924 had an odds ratio (OR) of 8.6, with a 95% confidence interval (CI) of 3.5-20.8, and homozygotes for the A allele of rs11200638 had an OR of 10.7, with a 95% CI of 3.2-35.7, for having AMD (p<0.00001). There was no association among these SNPs and phenotype or response to PDT. HTRA1 mRNA levels in WBCs were not associated with rs11200638 genotypes. CONCLUSIONS: The rs10490924 SNP in LOC387715/ARMS2 and the rs11200638 SNP in HTRA1 are strongly associated with NVAMD in this Israeli population. These variants do not have a major contribution to the variable phenotype and response to PDT which characterize NVAMD.

Chowers I, Cohen Y, Goldenberg-Cohen N, Vicuna-Kojchen J, Lichtinger A, Weinstein O, Pollack A, Axer-Siegel R, Hemo I, Averbukh E, Banin E, Meir T, Lederman M. · Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Hebrew University School of Medicine, Jerusalem, Israel. · Mol Vis. · Pubmed #18852870 links to  free full text

Abstract: PURPOSE: The Tyr402His variant of complement factor H (CFH) is associated with age-related macular degeneration (AMD) in several populations. Our aim was to evaluate if this single nucleotide polymorphism (SNP) is associated with AMD in the Israeli population and see if it underlies heterogeneity in clinical manifestation and responses to photodynamic therapy (PDT), which characterize neovascular AMD (NVAMD). METHODS: Genotyping for the Tyr402His variant was performed in 240 NVAMD patients (78.1+/-7 age range) and 118 controls (70.8+/-8.2 age range). Genotyping was correlated with clinical characteristics and treatment parameters in sequential 131 NVAMD patients who underwent PDT. RESULTS: TheTyr402His coding allele was associated with NVAMD in the Israeli population: odds ratio (OR)=1.9; 95% confidence interval (CI)=1.3-2.6; p=0.0002. Homozygosity for this variant was associated with an OR of 3.4 (95% CI: 1.7-6.8) for having AMD. There was no association among this SNP and age of onset of NVAMD, gender, neovascular lesion size, initial or final visual acuity, and number of PDT sessions required. CONCLUSIONS: In accordance with findings from the majority of previous study populations, the Tyr402His variant of CFH is associated with NVAMD in Israel. However, heterogeneity in clinical manifestations of NVAMD and in its response to PDT is not underlined by this CFH variant and may be accounted for by other genetic and environmental factors.

Ehrlich R, Weinberger D, Priel E, Axer-Siegel R. · Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, Israel. · Retina. · Pubmed #18664935 No free full text.

Abstract: OBJECTIVE: To study the effect of intravitreal bevacizumab for the treatment of long-standing exudative age-related macular degeneration (AMD) and low visual acuity. METHODS: Forty-seven patients (48 eyes) aged 57 to 90 years with AMD for 5 months or more and visual acuity of 20/150 or less were treated with one or more injections of bevacizumab 1.25 mg/0.05 mL between December 2005 and March 2007. The files were reviewed for background data, visual acuity, fluorescein angiography, retinal thickness, and complications. RESULTS: Thirty-two eyes were treated previously with photodynamic therapy. Mean duration of symptoms was 17.9 +/- 17.5 months; mean number of bevacizumab injections was 3.41 +/- 2; and mean follow-up was 27 +/- 15 weeks. Snellen visual acuity improved from 20/150 to hand movements (mean logMAR 1.34 +/- 0.29) to 20/50 to counting fingers (mean logMar 1.2 +/- 0.42) (P = 0.003, paired t-test). Visual acuity improved by> or =3 lines in 12 eyes (25%); showed no change in 9 eyes (19%); and deteriorated by > or =3 lines in 4 eyes (8.3%). Visual acuity was at least 20/150 in 16 eyes (33.3%) at the end of follow-up compared with 4 eyes (8.3%) before treatment (P = 0.02, McNemar test). Mean central retinal thickness (measured in 22 eyes) decreased from 324 +/- 121 mum to 264 +/- 65 mum (P = 0.02, paired t-test). CONCLUSIONS: Patients with chronic exudative AMD and low visual acuity may benefit from intravitreal bevacizumab injections.

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.

Ron Y, Ehrlich R, Axer-Siegel R, Rosenblatt I, Weinberger D. · Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel. · Ophthalmologica. · Pubmed #17183203 No free full text.

Abstract: PURPOSE: Subretinal hemorrhage is one of the most serious complications of exudative age-related macular degeneration (AMD). Treatment with vitreous surgery with or without plasminogen activator, fluid-gas exchange, or perfluorocarbon yields only a small improvement in visual acuity. PATIENTS AND METHODS: The files of 24 patients with submacular hemorrhage secondary to AMD who were treated by injection of perfluoropropane gas (C(3)F(8)) (11 patients) or sulfur hexafluoride (SF(6)) (13 patients) were reviewed for visual acuity before and after the procedure and time of treatment from onset of symptoms. RESULTS: For the whole sample, pneumatic displacement led to a statistically significant improvement in mean visual acuity (p = 0.015). A significant difference between pre- and postoperative visual acuity was found for the patients treated with SF(6) (p = 0.034), but not for the patients treated with C(3)F(8) (p = 0.245). CONCLUSION: The use of gas injection to displace submacular hemorrhage can significantly improve visual acuity.

Axer-Siegel R, Ehrlich R, Avisar I, Kramer M, Rosenblatt I, Priel E, Weinberger D. · Department of Ophthalmology Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel. · Ophthalmic Surg Lasers Imaging. · Pubmed #17152538 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: To report the outcome of combined verteporfin photodynamic therapy (PDT) and intravitreal triamcinolone acetonide (IVTA) for the treatment of choroidal neovascularization (CNV) with serous pigment epithelium detachment (PED) due to age-related macular degeneration (AMD). PATIENTS AND METHODS: The files of all consecutive patients with CNV and serous PED who received PDT and IVTA either primarily (primary treatment group) or following previous unsuccessful PDT (secondary treatment group) were reviewed for visual and angiographic results. RESULTS: Ten patients (11 eyes) were included. Mean number of PDT sessions was 3.18; 8 eyes received one IVTA injection and 3 eyes received two IVTA injections. Thirty-six percent of patients retained their initial visual acuity after a mean follow-up of 15.3 months. Loss of 3 or more Snellen lines was noted in 2 of 3 eyes in the primary treatment group and 5 of 8 eyes in the secondary treatment group. Increased intraocular pressure developed in 3 patients and was controlled by topical medications. CONCLUSIONS: Although combined PDT and IVTA may be considered for CNV with serous PED in patients with poor prognosis with PDT alone, the regimen as administered in this small series was not beneficial. Further studies are required to determine whether alternate sequences, timing, or doses would yield a better outcome.

Bahar I, Weinberger D, Kramer M, Axer-Siegel R. · Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel. · Retina. · Pubmed #16141876 No free full text.

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Axer-Siegel R, Ehrlich R, Rosenblatt I, Kramer M, Priel E, Yassur Y, Weinberger D. · Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tikva 49100, Israel. · Arch Ophthalmol. · Pubmed #15078661 No free full text.

Abstract: OBJECTIVE: To study the visual and angiographic outcome of eyes with neovascular age-related macular degeneration associated with pigment epithelium detachment (PED) treated by photodynamic therapy. METHODS: Review of the medical charts and the fluorescein and indocyanine green angiograms of all consecutive patients with age-related macular degeneration associated with choroidal neovascularization and serous PED of at least 1 disc diameter, who received photodynamic therapy from January 1, 2000, to August 31, 2002. RESULTS: Thirty patients (34 eyes) met the study criteria. Each underwent 1 to 8 treatments (mean, 4); duration of follow-up was 12 to 36 months (mean, 19 months). Nineteen eyes (56%) lost 3 or more Snellen lines of visual acuity, 7 eyes (21%) lost 1 or 2 lines, 6 eyes (18%) maintained their initial acuity, and 2 eyes (6%) gained 1 or 2 lines. Subretinal hemorrhage occurred in 5 eyes and retinal pigment epithelium tears in 4 eyes. In 4 eyes, visual acuity decreased to counting fingers, hand motions, or light perception. CONCLUSIONS: Although 44% of the 34 eyes with age-related macular degeneration and PED lost fewer than 3 Snellen lines in acuity, severe visual loss to counting fingers or less occurred in 4 eyes, 3 of them with choroidal neovascularization inside the PED. Further studies and treatment modalities are required to improve prognosis of neovascular age-related macular degeneration with serous PED.

Axer-Siegel R, Ehrlich R, Yassur Y, Rosenblatt I, Kramer M, Priel E, Benjamini Y, Weinberger D. · Department of Ophthalmology, Rabin Medical Center, Beilinson, Petah Tiqva, Israel. · Am J Ophthalmol. · Pubmed #14962414 No free full text.

Abstract: PURPOSE: To evaluate the visual outcome of patients with subfoveal choroidal neovascularization due to age-related macular degeneration, who received photodynamic therapy (PTD) in a clinical setting and to identify potential predictive visual and angiographic factors. DESIGN: Interventional case series. METHODS: The study included 74 patients with subfoveal choroidal neovascularization who underwent PDT from January 2000 to March 2001 and completed at least 1 year follow-up. All patients received verteporfin PDT and were followed clinically, with fluorescein angiography (74 eyes), and with indocyanine green angiography (65 eyes). A review of the medical records and angiograms was performed. RESULTS: Mean follow-up was 15.6 months. Patients received a mean of 3.4 treatments per year. Sixty-six percent lost less than 3 Snellen lines of visual acuity. Three patients (4%) experienced profound visual acuity loss to finger counting. Final visual acuity was positively correlated with lesion size and visual acuity at presentation. Visual outcome was worse in the presence of cystoid macular edema. On indocyanine green angiography, a round hypofluorescent spot was seen at the site of the PDT, with maintenance of medium and large choroidal vessels. CONCLUSION: Smaller lesion size and better visual acuity at presentation were good predictive signs, whereas cystoid macular edema was found to be a poor prognostic sign for visual outcome following PDT.

Axer-Siegel R, Bourla D, Ehrlich R, Dotan G, Benjamini Y, Gavendo S, Weinberger D, Sela BA. · Department of Ophthalmology, Rabin Medical Center, Petah Tiqva, Israel. · Am J Ophthalmol. · Pubmed #14700648 No free full text.

Abstract: PURPOSE: To assess the relationship between plasma homocysteine levels and exudative neovascular age-related macular degeneration (AMD). DESIGN: Cross-sectional study. METHODS: A prospective comparative cross-sectional study was conducted in outpatient ophthalmology clinics in a university-affiliated medical institution. The cohort consisted of 59 patients (25 male, 34 female) with a mean age of 78 years (standard deviation [SD] = 8.4) with neovascular AMD who were candidates for photodynamic treatment. Patients were compared for plasma homocysteine levels with 58 patients who had dry AMD (24 male, 34 female) with a mean age of 76.3 years (SD = 8.4) and with a control group of 56 age-matched subjects (27 male, 29 female), with a mean age of 77.3 years (SD = 8.2). A 3-ml venous blood sample was obtained from each participant after an 8-hour fast. Levels of plasma homocysteine were measured by high performance liquid chromatography. The main outcome measure was hyperhomocysteinemia, defined as a plasma homocysteine level above 15 micromol/l. RESULTS: Homocysteine levels were higher by 27.9% in the neovascular AMD than in the dry AMD group, and by 21.9% than in the control group (P <.02). Hyperhomocysteinemia was found in 44.1% of the study group, in 22.4% of the dry AMD group, and in 21.4% of the control group (P =.011). CONCLUSIONS: This study suggests an association between an elevated plasma level of homocysteine and exudative neovascular AMD but not dry AMD.

Axer-Siegel R, Bourla D, Priel E, Yassur Y, Weinberger D. · Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel. · Ophthalmology. · Pubmed #12208724 No free full text.

Abstract: OBJECTIVE: To identify the angiographic features of retinal choroidal anastomoses (RCAs) in patients with newly diagnosed occult choroidal neovascularization (CNV) in the setting of age-related macular degeneration (AMD) and to determine the sequence of flow between the RCA and the CNV. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: The angiograms of 205 eyes of 153 consecutive patients with occult CNV on fluorescein angiography (FA) and focal hot spots on indocyanine green angiography (ICGA) were evaluated retrospectively. METHODS OF TESTING: Red-free photographs and sequential digital fluorescein and indocyanine green angiograms obtained by confocal scanning laser ophthalmoscope (the Heidelberg Retina Angiograph; Heidelberg Engineering GmbH, Dossenheim, Germany). MAIN OUTCOME MEASURES: The angiograms were evaluated for the presence of RCA. The following angiographic characteristics were recorded: number and type of anastomoses, location, distance from fovea, area of CNV, presence of pigment epithelium detachment (PED), cystoid macular edema on FA, and intraretinal leakage on ICGA. The direction of flow between the RCA and the CNV was identified by analyzing high-speed angiograms. RESULTS: Retinal choroidal anastomoses were identified in 57 eyes (28%), in 49 of 154 eyes with PED (32%), and in 8 of 51 eyes without PED (16%). Of 109 anastomoses, 70% were venous and 30% were arterial. Ninety-six percent of the eyes had at least one venous anastomosis, 49% of the eyes had an arterial anastomosis, and 46% of the eyes had both. Cystoid macular edema was seen on FA in 37 eyes (65%), and intraretinal indocyanine green leakage was noted in 52 eyes (91%). Twenty-two eyes that underwent high-speed ICGA were analyzed for the direction of flow. All 15 eyes having arterial and venous anastomoses demonstrated a filling pattern from the retinal arteriole to the CNV, followed by the retinal venule. Seven eyes with venous RCA showed flow sequence from the CNV to the collecting retinal venule. CONCLUSIONS: Our study supports the presence of RCA in the early stages of acute exudative AMD with occult CNV, mainly with serous PED. High-speed angiography helps to identify the filling sequence of the RCA and the CNV, and therefore may guide the clinician in planning treatment strategies.

Weinberger D, Lichter H, Goldenberg-Cohen N, Priel E, Bahar I, Yassur Y, Axer-Siegel R. · Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel. · Retina. · Pubmed #12172105 No free full text.

Abstract: PURPOSE: To evaluate alterations in the retinal vasculature overlying pigment epithelial detachments (PED) in exudative age-related macular degeneration (ARMD) using indocyanine green and fluorescein angiography. METHODS: Forty-one patients (41 eyes) with a clinical diagnosis of exudative ARMD with PED underwent simultaneous fluorescein and indocyanine green angiography, also under high (10 degrees ) magnification. Vascular abnormalities in the retina were compared between patients with vascularized (n = 34, group 1) and nonvascularized (n = 7, group 2) PED on indocyanine green angiography and correlated with the size of the PED and the presence of serous retinal detachment. RESULTS: In all, 67 vascular abnormalities were found by indocyanine green angiography and only 22 by fluorescein angiography; this finding was statistically significant (P < 0.0001). The finding of retinal vasculopathy (32 patients in group 1 and two patients in group 2) was directly correlated with the presence of choroidal neovascularizations (P = 0.002). There was also a direct correlation between the presence of choroidal neovascularization and size of the PED (P = 0.03). The number of retinal vascular findings was not significantly correlated with serous elevation of the retina. CONCLUSIONS: Retinal vasculopathies may be observed in eyes with PED and are detectable by indocyanine green and fluorescein angiography.

Axer-Siegel R, Lichter H, Rosenblatt I, Priel E, Yassur Y, Weinberger D. · Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel. · Am J Ophthalmol. · Pubmed #10511028 No free full text.

Abstract: PURPOSE: To describe the indocyanine green angiographic pattern of retinal pigment epithelium tears in the setting of age-related macular degeneration compared with the fluorescein angiographic features. METHODS: Twelve consecutive patients (12 eyes) with a retinal pigment epithelium tear underwent simultaneous indocyanine green angiography and fluorescein angiography with the confocal scanning laser ophthalmoscope. The findings for the two modes were compared. RESULTS: Choroidal neovascular membrane was evident beneath the rolled retinal pigment epithelium on indocyanine green angiograms in 11(92%) of 12 eyes: a focal neovascular membrane was apparent in five (42%) of 12 eyes, whereas a plaque neovascular membrane was seen in six (50%) of 12 eyes. In comparison, fluorescein angiography demonstrated late leakage as a result of occult choroidal neovascular membrane in nine (82%) of 11 eyes but no well-defined choroidal neovascular membrane. CONCLUSIONS: Indocyanine green angiography is superior to fluorescein angiography for imaging choroidal neovascularization in cases of retinal pigment epithelium tear and may serve as an important adjunct to indocyanine green-guided laser treatment in selected cases.