Macular Degeneration: Dubovy SR

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.

Miller DM, Espinosa-Heidmann DG, Legra J, Dubovy SR, Sũner IJ, Sedmak DD, Dix RD, Cousins SW. · Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine, 900 NW 17th Street, Miami, FL 33136, USA. · Am J Ophthalmol. · Pubmed #15364212 No free full text.

Abstract: PURPOSE: To determine if prior exposure to pathogens associated with vascular disease, cytomegalovirus, Chlamydia pneumoniae, and Helicobacter pylori correlates with neovascular age-related macular degeneration (AMD). DESIGN: An experimental study. METHODS: SETTING: Institutional. Bascom Palmer Eye Institute, October 2001 to December 2002. PATIENT POPULATION: 150 patients (47 neovascular amd, 36 dry amd, and 67 non-amd controls) were included in the study. exclusion criteria included hiv infection, malignancy, recent acute illness requiring hospitalization within 6 months, or immunosuppressive illness. PROCEDURE: Serum samples were obtained for analysis of cytomegalovirus, chlamydia pneumoniae, and helicobacter pylori igg antibody titers by elisa. MAIN OUTCOME MEASURE: Comparison of the distribution of igg titers between patients with wet amd, dry amd, and controls. RESULTS: The average cytomegalovirus IgG titer was higher in patients with wet AMD versus controls (p = 0.02, Student t-test, two-tailed) and patients with dry AMD (p = 0.06). Twenty-six (55%) of 47 subjects with wet AMD had high cytomegalovirus IgG titers compared with 14 (39%) of 36 patients with dry AMD (odds ratio [OR] = 2.23, 95% confidence interval [CI] = 0.77 to 6.44) and 23 (34%) of 67 control patients (OR = 2.49, 95% CI = 0.98 to 6.33). There was no major difference in the distribution of titers for Chlamydia pneumoniae IgG and Helicobacter pylori IgG in wet and dry AMD patients. Five of 47 patients with wet AMD (11%) had high antibody titers to all three pathogens, compared with only 1 of 36 patients with dry AMD (3%) (OR = 4.17, 95% CI = 0.46 to 37.36). CONCLUSIONS: There was a significant association of high cytomegalovirus IgG titer with neovascular AMD compared with dry AMD and control patients. Chronic infection with cytomegalovirus may be a novel risk factor for the progression from dry to neovascular AMD.

Benz MS, Murray TG, Dubovy SR, Katz RS, Eifrig CW. · Bascom Palmer Eye Institute, PO Box 016880, Miami, FL 33101, USA. · Arch Ophthalmol. · Pubmed #12583797 No free full text.

This publication has no abstract.

Bailey TA, Alexander RA, Dubovy SR, Luthert PJ, Chong NH. · Department of Pathology, Institute of Ophthalmology, UCL, Bath Street, London, EC1V 9EL, UK. · Exp Eye Res. · Pubmed #11846515 No free full text.

Abstract: An increase or accumulation in tissue inhibitor of matrix metalloproteinases-3 (TIMP-3) protein in Bruch's membrane with ageing in normal eyes, and in age related macular degeneration (AMD) has been previously demonstrated. The purpose of this study was to determine whether the expression of TIMP-3 mRNA increases with age, and to define any relationship between altered expression and Bruch's membrane thickness. Normal eyes were obtained from 30 donors (age range 15-90 years). Full-thickness 8 mm macular punches centred on the fovea were taken to allow removal of the chorioretinal complex, for subsequent nucleic acid extraction. Samples were normalized for RNA degradation using beta-actin reverse transcriptase-polymerase chain reaction (RT-PCR). A competitive RT-PCR was then used to allow measurement of TIMP-3 gene expression in each sample. The tissue adjacent to that used for nucleic acid extraction was processed histologically to allow determination of Bruch's membrane thickness. Bruch's membrane thickness was found to increase with age (P < 0.01), but TIMP-3 expression, as measured by competitive RT-PCR, was not significantly increased with age (P = 0.19). An inverse correlation was noted between TIMP-3 expression and Bruch's membrane thickness after controlling for age (P = 0.032). The results of this study suggest that TIMP-3 expression does not alter significantly with age. Therefore, accumulation of the TIMP-3 protein must occur by a mechanism other than increased expression. TIMP-3 protein levels may still prove to contribute to events associated with ageing in the macula, such as matrix remodelling in Bruch's membrane. Further studies are required to elucidate the precise interactions and turnover of the TIMP-3 protein, and resulting changes in the control of matrix metalloproteinase activity in the ageing macula.

Dubovy SR, Hairston RJ, Schatz H, Schachat AP, Bressler NM, Finkelstein D, Green WR. · Wilmer Ophthalmological Institute, and Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. · Retina. · Pubmed #11131418 No free full text.

Abstract: PURPOSE: The authors describe the clinicopathologic features of three patients with adult onset foveomacular pigment epithelial dystrophy (AOFPED). METHODS: The eyes of three patients were studied ophthalmoscopically and by fluorescein angiography, and obtained postmortem and studied by light and electron microscopy. RESULTS: Histopathologic study of the three patient's eyes disclosed central loss of the retinal pigment epithelium and photoreceptor cell layer with a moderate number of pigment-containing macrophages present in the subretinal space and outer retina. To either side, the retinal pigment epithelium was distended with much lipofuscin. Basal laminar and basal linear deposits were present throughout the central area. No discontinuities of Bruch membrane were present. CONCLUSION: The findings in the eyes of three patients with AOFPED included marked aging changes that are similar to those seen in age-related macular degeneration. Pigmented cells with lipofuscin in the subretinal space account for the vitelliform appearance.