Macular Degeneration: Maia M

Furlani BA, Meyer CH, Rodrigues EB, Maia M, Farah ME, Penha FM, Holz FG. · Federal University of Sao Paulo, Vision Institute, Department of Ophthalmology, Sao Paulo, Brazil. · Expert Opin Emerg Drugs. · Pubmed #17979601 No free full text.

Abstract: Diabetic macular edema (DME) is the most frequent cause of severe vision impairment in patients with non-proliferative diabetic retinopathy. Even though patients should achieve optimal glycemic control, normalization of blood pressure and serum lipids, as well as improvement of cardiac and renal status, these measures alone will not prevent every patient from developing visual loss caused by DME. The goal of local treatment for DME is vision improvement, usually achieved after reducing leakage on fluorescein angiography (FA) and retinal thickness on optical coherence tomography (OCT). Laser photocoagulation is still the standard treatment for clinically significant DME. However, laser photocoagulation rarely provides major visual improvement, especially in patients with diffuse DME. Thus, a therapeutic intervention that restores visual acuity impaired by DME more often remains a significant unmet medical need. This review aims to present the most important emerging drug technologies for therapy of DME at present, including corticosteroids, vascular endothelial growth factor inhibitors, protein kinase C inhibitors, small interfering RNA, hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors and non-hormonal anti-inflammatory agents. Recent progress in this field suggests that local management of DME may change rapidly in the near future. Novel emerging drugs should enable better anatomical and functional outcomes for therapy of this sight-threatening disease.

Margalit E, Maia M, Weiland JD, Greenberg RJ, Fujii GY, Torres G, Piyathaisere DV, O'Hearn TM, Liu W, Lazzi G, Dagnelie G, Scribner DA, de Juan E, Humayun MS. · Intraocular Prosthesis Group, Wilmer Eye Institute, Johns Hopkins, Baltimore, MD 21287-9277, USA. · Surv Ophthalmol. · Pubmed #12161210 No free full text.

Abstract: Most of current concepts for a visual prosthesis are based on neuronal electrical stimulation at different locations along the visual pathways within the central nervous system. The different designs of visual prostheses are named according to their locations (i.e., cortical, optic nerve, subretinal, and epiretinal). Visual loss caused by outer retinal degeneration in diseases such as retinitis pigmentosa or age-related macular degeneration can be reversed by electrical stimulation of the retina or the optic nerve (retinal or optic nerve prostheses, respectively). On the other hand, visual loss caused by inner or whole thickness retinal diseases, eye loss, optic nerve diseases (tumors, ischemia, inflammatory processes etc.), or diseases of the central nervous system (not including diseases of the primary and secondary visual cortices) can be reversed by a cortical visual prosthesis. The intent of this article is to provide an overview of current and future concepts of retinal and optic nerve prostheses. This article will begin with general considerations that are related to all or most of visual prostheses and then concentrate on the retinal and optic nerve designs. The authors believe that the field has grown beyond the scope of a single article so cortical prostheses will be described only because of their direct effect on the concept and technical development of the other prostheses, and this will be done in a more general and historic perspective.

Arevalo JF, Fromow-Guerra J, Quiroz-Mercado H, Sanchez JG, Wu L, Maia M, Berrocal MH, Solis-Vivanco A, Farah ME, Anonymous00408. · Retina and Vitreous Service, Clinica Oftalmológica Centro Caracas, Caracas, Venezuela. · Ophthalmology. · Pubmed #17398322 No free full text.

Abstract: PURPOSE: To report the 6-month anatomic and best-corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (Avastin) in patients with diabetic macular edema (DME). DESIGN: Interventional retrospective multicenter study at 6 centers from 6 countries of patients with DME. PARTICIPANTS: We reviewed the clinical records of 88 consecutive patients (110 eyes) with DME. Seventy-eight eyes of 64 consecutive patients with a minimum follow-up of 6 months and mean age of 59.7+/-9.3 years were included in this analysis. INTERVENTION: Patients were treated with at least one intravitreal injection of 1.25 mg or 2.5 mg of bevacizumab and underwent Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA testing, ophthalmoscopic examination, optical coherence tomography (OCT), and fluorescein angiography (FA) at baseline and follow-up visits. Repeated-measures analysis of variance was used to compare mean values. MAIN OUTCOME MEASURES: Changes in BCVA, OCT, and FA. RESULTS: Mean follow-up was 6.31+/-0.81 months (range, 6-9). Sixteen (20.5%) eyes needed a second injection at a mean of 13.8 weeks (range, 4-28), and 6 eyes needed a third injection (7.7%) at a mean of 11.5 weeks (range, 5-20). The mean baseline BCVA was 0.87 (logarithm of the minimum angle of resolution), and the final mean BCVA was 0.6, a difference that was statistically significant (P<0.0001). Final BCVA analysis by subgroups demonstrated that 32 (41.1%) eyes remained stable, 43 (55.1%) improved > or =2 ETDRS lines of BCVA, and 3 (3.8%) decreased > or =2 ETDRS lines of BCVA. Mean central macular thickness at baseline by OCT was 387.0+/-182.8 mum and decreased to a mean of 275.7+/-108.3 at end of follow-up (P<0.0001). No ocular or systemic adverse events were observed. CONCLUSIONS: Primary intravitreal bevacizumab at doses of 1.25 to 2.5 mg seem to provide stability or improvement in VA, OCT, and FA in DME at 6 months. Follow-up is still short to make any specific treatment recommendations; however, the results appear promising. Evaluation in a multicenter randomized controlled clinical trial with longer follow-up is needed.

Wu L, Fernando Arevalo J, Maia M, Berrocal MH, Sanchez J, Evans T, Anonymous00035. · Instituto de Cirugia Ocular, San Jose, Costa Rica. · Jpn J Ophthalmol. · Pubmed #19333696 No free full text.

Abstract: PURPOSE: To compare the total number of injections and the anatomic and best-corrected visual acuity (VA) response after injecting 1.25 or 2.5 mg of bevacizumab as needed in patients with primary choroidal neovascularization secondary to age-related macular degeneration (AMD) at 12 months. METHODS: This was a retrospective, interventional, comparative multicenter study of 60 eyes treated with intravitreal bevacizumab (35 eyes, 1.25 mg; 25 eyes, 2.5 mg). RESULTS: The mean number of injections per eye was 3.8 in the 1.25-mg group and 3.2 in the 2.5-mg group (P = 0.2752). At 12 months, in the 1.25-mg group, 16 (46%) eyes gained > or =3 lines of Early Treatment Diabetic Retinopathy Study (ETDRS) VA and seven (20%) lost > or =3 lines of ETDRS VA. In the 2.5-mg group, 11 (44%) eyes improved by > or =3 lines, and four (16%) lost > or =3 lines (P = 1.000). At 12 months, in the 1.25-mg group, the mean central macular thickness decreased from 419 +/- 201 microm at baseline to 268 +/- 96 microm, compared with a decrease from 388 +/- 162 to 296 +/- 114 microm in the 2.5-mg group (P = 0.7896). CONCLUSION: There were no statistically significant differences between the two dose groups with regard to the number of injections, anatomic and VA outcomes.

Arevalo JF, Fromow-Guerra J, Sanchez JG, Maia M, Berrocal MH, Wu L, Saravia MJ, Costa RA, Anonymous00093. · Retina and Vitreous Service, Clinica Oftalmológica Centro Caracas, Caracas, Venezuela. · Retina. · Pubmed #18827735 No free full text.

Abstract: PURPOSE: To report the 12-month anatomic and Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (Avastin, Genentech Inc., San Francisco, CA) (1.25 mg or 2.5 mg) in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration. METHODS: Sixty-three eyes of 63 consecutive patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration, a mean age of 73.7 +/- 7.5 years and a minimum of 12 months (mean 55.5 +/- 6.2 weeks) of follow-up participated in this interventional retrospective multicenter case series in 7 centers from 6 countries. Patients were treated with at least 1 intravitreal injection of 1.25 mg or 2.5 mg of bevacizumab. Patients underwent Early Treatment Diabetic Retinopathy Study BCVA testing, ophthalmoscopic examination, optical coherence tomography, and fluorescein angiography at baseline and follow-up visits. Repeated measures analysis of variance was used to compare mean values. RESULTS: The mean number of intravitreal bevacizumab injections per eye was 3.5 (range, 1-8). Mean baseline BCVA was 20/320, logarithm of the minimum angle of resolution = 1.2, and mean final BCVA was 20/200, logarithm of the minimum angle of resolution = 1.0 (P < 0.001). Central macular thickness at baseline by optical coherence tomography had a mean of 389.2 +/- 149.6 microm which was significantly reduced to a mean of 281.0 +/- 96.1 microm, 268.2 +/- 82.6 microm, 262.6 +/- 92.3 microm, and 241.3 +/- 76.7 microm at 1, 3, 6, and 12 months after initial treatment, respectively (P < 0.0001). Ocular adverse events included transient increased intraocular pressure in 2 (3.1%) eyes, endophthalmitis in 2 (3.1%) eyes, and transient hypotony in 1 eye (1.1%). No systemic adverse events were observed. CONCLUSION: Primary intravitreal bevacizumab at doses of 1.25 mg or 2.5 mg seems to provide stability or improvement in BCVA, optical coherence tomography, and fluorescein angiography in subfoveal choroidal neovascularization secondary to age-related macular degeneration at 12 months.

Wu L, Arevalo JF, Roca JA, Maia M, Berrocal MH, Rodriguez FJ, Evans T, Costa RA, Cardillo J, Anonymous00059. · Instituto de Cirugia Ocular, San José, Costa Rica. · Retina. · Pubmed #18301025 No free full text.

Abstract: PURPOSE: To report the 6-month anatomical and visual outcomes after injecting two different doses of intravitreal bevacizumab in patients with macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: An interventional, retrospective multicenter study of 45 eyes that were treated with at least one intravitreal injection (24 eyes, 1.25 mg; 21 eyes, 2.5 mg) of bevacizumab is reported. The main outcome measures were the central 1-mm macular thickness (CMT) and the change in ETDRS lines of best-corrected visual acuity (BCVA) at 6 months. RESULTS: Forty-five eyes were injected on average 26.1 months (range, 3-86 months) after the diagnosis. The average follow-up was 35.2 weeks (range, 24-52 weeks). All patients completed at least 6 months of follow-up. In the 1.25-mg dose group, at 1 month, there was an average gain of 4.5 lines of BCVA; at 3 months, 5.1 lines of BCVA; and at 6 months, 5.1 lines of BCVA (P < 0.005). In the 2.5-mg dose group, at 1 month, there was an average gain of 2.3 lines of BCVA; at 3 months, 3.8 lines of BCVA; and at 6 months, 4.8 lines of BCVA (P = 0.05). In the 1.25-mg dose group, the mean CMT +/- SD decreased from 461 +/- 211 microm at baseline to 321 +/- 152 microm at 1 month, 273 +/- 99 microm at 3 months, and 277 +/- 114 microm at 6 months (P = 0.0002). In the 2.5-mg group, the mean CMT +/- SD decreased from 385 +/- 168 microm at baseline to 279 +/- 111 microm at 1 month, 249 +/- 97 microm at 3 months, and 240 +/- 93 microm at 6 months (P = 0.011). CONCLUSION: There were no statistically significant differences between the two dose groups with regard to the number of injections and anatomical and functional outcomes. Intravitreal injection of bevacizumab at doses up to 2.5 mg appears to be effective in improving BCVA and reducing CMT in BRVO in the short term. Multiple injections are needed in a large number of eyes for continued control of macular edema and preservation of visual acuity in the short term. Longer studies are needed to determine what role if any intravitreal injection of bevacizumab may play in the long-term treatment of this condition.

Arevalo JF, Garcia-Amaris RA, Roca JA, Sanchez JG, Wu L, Berrocal MH, Maia M, Anonymous00337. · Retina and Vitreous Service, Clinica Oftalmológica Centro Caracas, Caracas, Venezuela. · J Cataract Refract Surg. · Pubmed #18053911 No free full text.

Abstract: PURPOSE: To determine the feasibility, safety, and clinical effect of primary intravitreal bevacizumab (Avastin) in patients with cystoid macular edema (CME) after cataract surgery. SETTING: Five institutions in Venezuela, Costa Rica, Puerto Rico, Peru, and Brazil. METHODS: Twenty-eight eyes of 25 patients treated with at least 1 intravitreal injection of 1.25 mg or 2.50 mg of Avastin participated in this interventional retrospective multicenter study at 5 institutions from 5 countries. Baseline and follow-up visits included Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing, optical coherence tomography (OCT) imaging, and ophthalmoscopic examination. RESULTS: The mean follow-up was 32 weeks (range 24 to 52 weeks). Twenty eyes (71.4%) had improved best corrected visual acuity (BCVA) (> or =2 ETDRS lines), and no eye had worse visual acuity (> or =2 ETDRS lines). The BCVA remained stable in 8 eyes (28.6%). The mean baseline BCVA was 20/160 (logMAR = 0.92) and the mean final BCVA, 20/63 (logMAR = 0.50); the difference was statistically significant (P<.0001). The mean central macular thickness at baseline (466.3 microm; range 208 to 784 microm) decreased significantly (264.5 microm; range 176 to 513 microm) by the end of follow-up (P<.0001). Eight eyes (28.6%) required a second injection and 4 (14.3%), a third injection. The mean interval between injections was 13 weeks (range 5 to 26 weeks). No ocular or systemic adverse events were observed. CONCLUSIONS: Short-term results suggest that primary intravitreal Avastin is well tolerated in patients with pseudophakic CME. Treated eyes had a significant improvement in BCVA and decrease in macular thickness by OCT.

Lowe J, Araujo J, Yang J, Reich M, Oldendorp A, Shiu V, Quarmby V, Lowman H, Lien S, Gaudreault J, Maia M. · Department of BioAnalytical R&D, MS38, Genentech, Inc., One DNA Way, South San Francisco, CA 94080-4990, USA. · Exp Eye Res. · Pubmed #17714704 No free full text.

Abstract: Neovascular age-related macular degeneration (AMD) is the leading cause of blindness in older adults in the Western world. Ranibizumab (Lucentis), a humanized antibody fragment directed against vascular endothelial growth factor (VEGF-A), was recently approved by the US Food and Drug Administration (FDA) for the treatment of neovascular AMD. The objective of this study was to characterize the binding affinity and pharmacological activity of ranibizumab for 3 biologically active forms of VEGF-A: VEGF165, VEGF121, and VEGF110. The apparent equilibrium binding affinity of ranibizumab for VEGF-A molecules was determined by Biacore analysis; the biological activity of VEGF-A was demonstrated in a human umbilical vein endothelial cell (HUVEC) proliferation-inhibition assay. Inhibition of VEGF-A-induced vascular permeability by ranibizumab was assessed in vivo using hairless guinea pigs and a modified Miles assay. Ranibizumab was capable of binding to recombinant human VEGF165, VEGF121, and VEGF110 (KD < or = 192 pM), inhibiting VEGF-A-induced HUVEC proliferation in a concentration-dependent manner. Ranibizumab also exerted potent dose-dependent inhibition (IC(50) of 0.4-1.2 nM) of the vascular permeability-enhancing activity of VEGF165, VEGF121, and VEGF110 in the Miles assay. In conclusion, these results show that ranibizumab is capable of binding to and specifically inhibiting the activities of 3 biologically active forms of VEGF-A. As VEGF-A plays a pivotal role in the pathogenesis of neovascular AMD, ranibizumab activity, as demonstrated in this study, supports its clinical utility in the treatment of this disease.

Wu L, Martínez-Castellanos MA, Quiroz-Mercado H, Arevalo JF, Berrocal MH, Farah ME, Maia M, Roca JA, Rodriguez FJ, Anonymous00001. · Instituto de Cirugía Ocular, San José, Costa Rica. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #17674014 No free full text.

Abstract: BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in many diseases of the posterior pole that are characterized by macular edema and/or intraocular neovascularization. Recently anti-VEGF agents such as ranibizumab and pegaptanib sodium have been shown to be beneficial in the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (ARMD). However in most parts of the world, both pegaptanib sodium and ranibizumab are not readily available. Bevacizumab, a humanized recombinant monoclonal IgG antibody that binds and inhibits all VEGF isoforms, has been proposed as an alternative treatment option. METHODS: A total of 1,265 consecutive patients were injected with bevacizumab for diseases such as proliferative diabetic retinopathy, diabetic macular edema, retinal vein occlusions, and CNV of several etiologies including ARMD at eight Latin American institutions from 1 September 2005 to 31 January 2006. Of these 1,265, 92 were excluded because they were injected once and lost to follow-up. The remaining 1,173 patients constitute the subjects of this retrospective, multicenter, open label, uncontrolled interventional case series that reports the cumulative systemic and ocular adverse events following intravitreal bevacizumab during 12 months of follow-up. Patients were examined at baseline and then monthly. If the patients were unable to attend the 12-month visit, a telephone interview was conducted to assess for possible systemic complications. RESULTS: A total of 4,303 intravitreal injections of bevacizumab on 1,310 eyes was reported. All 1,173 patients were accounted for at the 12-month visit. Systemic adverse events were reported in 18 (1.5%) patients. These included seven (0.59%) cases of an acute elevation of systemic blood pressure, six (0.5%) cerebrovascular accidents, five (0.4%) myocardial infarctions, two (0.17%) iliac artery aneurysms, two (0.17%) toe amputations and five (0.4%) deaths. Ocular complications included seven (0.16%) bacterial endophthalmitis, seven (0.16%) tractional retinal detachments, four (0.09%) uveitis, and a case (0.02%) each of rhegmatogenous retinal detachment and vitreous hemorrhage. CONCLUSION: Despite the limited follow-up, repeated intravitreal injections of either 1.25 mg or 2.5 mg of bevacizumab appears to be safe and well tolerated during the 1st year.