Macular Degeneration: Brucker AJ

Anonymous00148, Brucker AJ, Qin H, Antoszyk AN, Beck RW, Bressler NM, Browning DJ, Elman MJ, Glassman AR, Gross JG, Kollman C, Wells JA. · No affiliation provided · Arch Ophthalmol. · Pubmed #19204228 No free full text.

Abstract: OBJECTIVE: To compare the effects of single-sitting vs 4-sitting panretinal photocoagulation (PRP) on macular edema in subjects with severe nonproliferative or early proliferative diabetic retinopathy with relatively good visual acuity and no or mild center-involved macular edema. METHODS: Subjects were treated with 1 sitting or 4 sittings of PRP in a nonrandomized, prospective, multicentered clinical trial. Main Outcome Measure Central subfield thickness on optical coherence tomography (OCT). RESULTS: Central subfield thickness was slightly greater in the 1-sitting group (n = 84) than in the 4-sitting group (n = 71) at the 3-day (P = .01) and 4-week visits (P = .003). At the 34-week primary outcome visit, the slight differences had reversed, with the thickness being slightly greater in the 4-sitting group than in the 1-sitting group (P = .06). Visual acuity differences paralleled OCT differences. CONCLUSIONS: Our results suggest that clinically meaningful differences are unlikely in OCT thickness or visual acuity following application of PRP in 1 sitting compared with 4 sittings in subjects in this cohort. More definitive results would require a large randomized trial. Application to Clinical Practice These results suggest PRP costs to some patients in terms of travel and lost productivity as well as to eye care providers could be reduced. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00687154.

Brucker AJ. · Department of Ophthalmology, Scheie Eye Institute, Philadelphia, Pennsylvania 19104, USA. · Retina. · Pubmed #19553791 No free full text.

Abstract: Age-related macular degeneration (AMD) is a significant source of morbidity in aging adults. The damage to the macula and vision loss in advanced forms of wet AMD stems from choroidal neovascularization that originates in the choroid and proliferates through breaks in the Bruch membrane. Although inhibitors of angiogenesis have been a recent advance in the treatment of AMD associated with neovascularization, these agents do not appear to cure the condition. Rather, antiangiogensis agents halt or slow progression of AMD in most cases. The development of additional treatments to provide more effective disease control may depend on addressing several pathophysiologic processes simultaneously. The search for more effective treatments will require a better understanding of the different physiologic processes involved with this disease process.

Ranchod TM, Brucker AJ, Liu C, Cukras CA, Hopkins TB, Ying GS. · Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. · Am J Ophthalmol. · Pubmed #19195634 No free full text.

Abstract: PURPOSE: To determine the accuracy of the photodynamic therapy (PDT) laser spot size on the retina as generated by 2 Food and Drug Administration (FDA)-approved lasers. DESIGN: Prospective observational case series. METHODS: Fundus photographs were taken of 1 eye of each of 10 subjects with the WinStation 4000 fundus photography system (OIS; Ophthalmic Imaging Systems, Sacramento, California, USA); disc size was calculated using OIS software. Slit-lamp photographs were taken of the PDT laser spot focused on the retina adjacent to the optic disc, using various spot sizes in combination with 3 different contact lenses and 2 different lasers. Spot size at the retina was determined by measuring the ratio of disc diameter to spot diameter in Adobe Photoshop (San Jose, California, USA) and applying this ratio to the OIS disc measurements. RESULTS: Spot size at the retina averaged 87% of expected spot size for the Coherent Opal laser (Coherent Inc, Santa Clara, California, USA) and 104% of expected spot size for the Zeiss Visulas laser (Carl Zeiss Meditec Inc, Dublin, California, USA)(P = .002). Multivariate analysis demonstrated that percentage of expected spot size decreased with larger spot diameter (P = .01 for Coherent laser; P = .02 for Zeiss laser). CONCLUSIONS: PDT spot size at the retina appears to be consistently smaller than expected for the Coherent laser while the spot size was consistently within 10% of expected size for the Zeiss laser. The deviation from expected size increased with larger spot size using the Coherent laser.

Metelitsina TI, Grunwald JE, DuPont JC, Ying GS, Brucker AJ, Dunaief JL. · Department of Ophthalmology, Scheie Eye Institute, School of Medicine, University of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104, USA. · Invest Ophthalmol Vis Sci. · Pubmed #18172113 links to  free full text

Abstract: PURPOSE: To investigate in a longitudinal study whether foveolar choroidal blood flow changes are associated with the development of choroidal neovascularization (CNV) in AMD. METHODS: Relative foveolar choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBFlow) were assessed in 135 patients with AMD, at baseline and then annually with laser Doppler flowmetry. All study eyes had visual acuity of 20/40 or better and no CNV at the time of enrollment. Comparison of foveolar choroidal circulatory measurements at baseline and their change before the development of CNV was made between eyes that had CNV and those that did not. RESULTS: CNV developed in 28 eyes during the study. Baseline average foveolar ChBVol and ChBFlow in these eyes were 24% (P < 0.0001) and 20% (P = 0.0007) lower than that observed in the 165 eyes in which CNV did not develop. In the eyes with CNV, foveolar ChBVol and ChBFlow decreased by 9.6% and 11.5% before the formation of CNV, whereas in the eyes that did not, they increased by 6.7% (P = 0.006) and 2.8% (P = 0.004), respectively. Eyes with lower baseline foveolar ChBFlow were more likely (risk ratio = 3.47, 95% CI: 1.24-8.70) to show visual loss of three or more lines than were eyes with a higher baseline ChBFlow (P = 0.005). CONCLUSIONS: The development of CNV and visual loss are associated with lower choroidal circulatory parameters at baseline. In addition, the results suggest that decreases in the foveolar choroidal circulation precede the development of CNV in AMD and may play some role in its development.

Singerman LJ, Brucker AJ, Jampol LM, Lim JI, Rosenfeld P, Schachat AP, Spaide RF. · Retina Associates of Cleveland, Cleveland, OH, USA. · Retina. · Pubmed #16208185 No free full text.

Abstract: Several recent developments may provide an opportunity to improve outcome in individuals who develop neovascular age-related maculopathy (age-related macular degeneration [ARMD]). Concurrent with progress in isolating clinically relevant subtypes of neovascular ARMD, several therapies have been introduced that show promise for halting progression of this disorder. However, data from controlled clinical trials to test the relative efficacy of different management strategies across these subtypes of disease presentation remain limited. In addition, strategies to control ARMD may evolve quickly as more is learned about how specific molecular events, such as cell-mediated inflammation and angiogenesis, contribute to disease expression. A roundtable of investigators was convened to discuss and summarize recent progress in the treatment of ARMD. Case studies were then presented to provide an opportunity for experts to reveal their specific thought processes in the approach to neovascular ARMD based on their own interpretation of current clinical data and empirical experience.

Tolentino MJ, Brucker AJ, Fosnot J, Ying GS, Wu IH, Malik G, Wan S, Reich SJ. · Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104, USA. · Retina. · Pubmed #15076954 No free full text.

Abstract: PURPOSE: To determine the safety and efficacy of small interfering RNA (siRNA) directed against vascular endothelial growth factor (VEGF) in a nonhuman primate model of laser-induced choroidal neovascularization (CNV). METHODS: Each animal received laser rupture of Bruch's membrane to induce CNV in both eyes. Each animal was then randomized to receive 0.05 mL of either vehicle alone or VEGF siRNA at 70 microg, 150 microg, or 350 microg in both eyes by intravitreal injection. Eyes were monitored weekly by ophthalmic examination, color photography, and fluorescein angiography for 36 days after laser injury. Electroretinograms were measured at baseline and at 5 weeks after laser. CNV on fluorescein angiograms were measured for area and graded for clinically significant leakage in a standardized, randomized, and double-masked fashion on days 15, 22, 29, and 36 after laser. RESULTS: VEGF siRNA did not cause any change in electroretinographic, hemorrhage, inflammation, or clinical signs of toxicity. A single administration of VEGF siRNA significantly inhibited growth of CNV and attenuated angiographic leakage in a dose-dependent manner. CONCLUSION: Intravitreal injection of VEGF siRNA is capable of inhibiting the growth and vascular permeability of laser-induced CNV in a nonhuman primate in a dose-dependent manner. This study demonstrates preclinical proof of a principle that supports proceeding to clinical studies of VEGF siRNA in patients with exudative age-related macular degeneration.