Macular Degeneration: Lalwani GA

Rosenfeld PJ, Rich RM, Lalwani GA. · Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, 900 NW 17th Street, Miami, FL 33136, USA. · Ophthalmol Clin North Am. · Pubmed #16935211 No free full text.

Abstract: Ranibizumab therapy is the first treatment for neovascular AMD to improve vision for most patients. The benefits apply to all angiographic subtypes of neovascular AMD and across all lesion sizes. Although the pivotal phase III trials (MARINA and ANCHOR) used monthly injections of ranibizumab for 2 years, the ongoing PIER, PrONTO, and SAILOR trials are investigating less frequent dosing regimens, and preliminary results from the PrONTO study suggest that fewer injections will most likely result in visual acuity improvements similar to the results from the phase III trials. When comparing the ANCHOR results with the FOCUS results, it also becomes apparent that the combination of ranibizumab with PDT does not necessarily result in better visual acuity outcomes, and the use of PDT may even reduce the visual acuity benefits achieved with ranibizumab alone (see Figs. 1-3). It seems unlikely that combination therapy provides any significant advantage over ranibizumab alone unless the combination of PDT and ranibizumab can decrease the need for frequent retreatment. The results from the PrONTO Study already suggest that less frequent treatment with ranibizumab is possible by using a variable dosing regimen with OCT. Ranibizumab also seems to be safe, with the 2-year MARINA data showing no increase in the incidence of systemic adverse events that could be associated with anti-VEGF therapy, such as myocardial infarction and stroke. There was a hint of a safety concern, however, in the pooled 1-year safety results from the MARINA and ANCHOR trials. Although the combined rate of myocardial infarction and stroke during the first year of the ANCHOR and MARINA trials was similar in the control and the 0.3-mg ranibizumab arms (1.3% and 1.6% respectively), these adverse events were slightly higher in the 0.5-mg ranibizumab arm (2.9%). These differences are not statistically significant, however, and probably do not represent a dose-dependent increase in risk because the 2-year results from the MARINA trial with the same monthly injection regimen showed no increased risk of thromboembolic events. In December 2005, Genentech submitted a Biologics License Application to the FDA for the use of ranibizumab in the treatment of neovascular wet AMD based on 1-year clinical efficacy and safety data from the two pivotal phase III trials, ANCHOR and MARINA, and the phase I-II FOCUS trial. Genentech has been granted a 6-month Priority Review from the FDA with a decision anticipated 6 months from the December submission date or by the end of June 2006 [29]. By the summer of 2006, this revolutionary therapy should be available for the treatment of neovascular AMD. At that time, the major dilemma facing most retina specialists will be whether to use intravitreal ranibizumab or intravitreal bevacizumab, the low cost alternative, for the treatment of neovascular AMD.

Lalwani GA, Rosenfeld PJ, Fung AE, Dubovy SR, Michels S, Feuer W, Davis JL, Flynn HW, Esquiabro M. · Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida 33136, USA. · Am J Ophthalmol. · Pubmed #19376495 No free full text.

Abstract: PURPOSE: To assess the long-term efficacy of a variable-dosing regimen with ranibizumab in the Prospective Optical Coherence Tomography (OCT) Imaging of Patients with Neovascular Age-Related Macular Degeneration (AMD) Treated with intraOcular Ranibizumab (PrONTO) Study, patients were followed for 2 years. DESIGN: A 2-year prospective, uncontrolled, variable-dosing regimen with intravitreal ranibizumab based on OCT. METHODS: In this open-label, prospective, single-center, uncontrolled clinical study, AMD patients with neovascularization involving the central fovea and a central retinal thickness (CRT) of at least 300 microm as measured by OCT were enrolled to receive 3 consecutive monthly intravitreal injections of ranibizumab (0.5 mg) [Lucentis; Genentech Inc, South San Francisco, California, USA]. During the first year, retreatment with ranibizumab was performed at each monthly visit if any criterion was fulfilled such as an increase in OCT-CRT of at least 100 microm or a loss of 5 letters or more. During the second year, the retreatment criteria were amended to include retreatment if any qualitative increase in the amount of fluid was detected using OCT. RESULTS: Forty patients were enrolled and 37 completed the 2-year study. At month 24, the mean visual acuity (VA) improved by 11.1 letters (P < .001) and the OCT-CRT decreased by 212 microm (P < .001). VA improved by 15 letters or more in 43% of patients. These VA and OCT outcomes were achieved with an average of 9.9 injections over 24 months. CONCLUSIONS: The PrONTO Study using an OCT-guided variable-dosing regimen with intravitreal ranibizumab resulted in VA outcomes comparable with the outcomes from the phase III clinical studies, but fewer intravitreal injections were required.

Fung AE, Lalwani GA, Rosenfeld PJ, Dubovy SR, Michels S, Feuer WJ, Puliafito CA, Davis JL, Flynn HW, Esquiabro M. · Pacific Eye Associates, California Pacific Medical Center, San Francisco, California, USA. · Am J Ophthalmol. · Pubmed #17386270 No free full text.

Abstract: PURPOSE: To evaluate an optical coherence tomography (OCT)-guided, variable-dosing regimen with intravitreal ranibizumab for the treatment of patients with neovascular age-related macular degeneration (AMD). DESIGN: Open-label, prospective, single-center, nonrandomized, investigator-sponsored clinical study. METHODS: In this two-year study, neovascular AMD patients with subfoveal choroidal neovascularization (CNV) (n = 40) and a central retinal thickness of at least 300 microm as measured by OCT were enrolled to receive three consecutive monthly intravitreal injections of ranibizumab (0.5 mg). Thereafter, retreatment with ranibizumab was performed if one of the following changes was observed between visits: a loss of five letters in conjunction with fluid in the macula as detected by OCT, an increase in OCT central retinal thickness of at least 100 microm, new-onset classic CNV, new macular hemorrhage, or persistent macular fluid detected by OCT at least one month after the previous injection of ranibizumab. RESULTS: At month 12, the mean visual acuity improved by 9.3 letters (P < .001) and the mean OCT central retinal thickness decreased by 178 microm (P < .001). Visual acuity improved 15 or more letters in 35% of patients. These visual acuity and OCT outcomes were achieved with an average of 5.6 injections over 12 months. After a fluid-free macula was achieved, the mean injection-free interval was 4.5 months before another reinjection was necessary. CONCLUSION: This OCT-guided, variable-dosing regimen with ranibizumab resulted in visual acuity outcomes similar to the Phase III clinical studies, but required fewer intravitreal injections. OCT appears useful for determining when retreatment with ranibizumab is necessary.

Rich RM, Rosenfeld PJ, Puliafito CA, Dubovy SR, Davis JL, Flynn HW, Gonzalez S, Feuer WJ, Lin RC, Lalwani GA, Nguyen JK, Kumar G. · Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine, FL 33136, USA. · Retina. · Pubmed #16770255 No free full text.

Abstract: PURPOSE: To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin, Genentech Inc.) for the treatment of neovascular age-related macular degeneration (ARMD). METHODS: A retrospective review was performed on consented patients with neovascular ARMD receiving intravitreal bevacizumab therapy. All patients received intravitreal bevacizumab at baseline with additional monthly injections given at the discretion of the treating physician. At each visit, a routine Snellen visual acuity assessment was performed followed by an ophthalmic examination and optical coherence tomography (OCT) imaging. RESULTS: Fifty-three eyes of 50 patients received an intravitreal bevacizumab injection between May and August 2005. Including the month 3 visit, the average number of injections was 2.3 out of a maximum of 4 injections. No serious drug-related ocular or systemic adverse events were identified. Improvements in visual acuity and central retinal thickness measurements were evident by week 1 and continued through month 3. At month 3, the mean visual acuity improved from 20/160 to 20/125 (P < 0.001) and the mean central retinal thickness decreased by 99.6 microm (P < 0.001). CONCLUSION: Off-label intravitreal bevacizumab therapy for neovascular ARMD was well tolerated over 3 months with improvements in visual acuity and OCT central retinal thickness measurements. While the long-term safety and efficacy of intravitreal bevacizumab remain unknown, these short-term results suggest that intravitreal bevacizumab may be the most cost effective therapy for the treatment of neovascular ARMD.