Macular Degeneration: Wilson DJ

Hawkins BS, Bressler NM, Miskala PH, Bressler SB, Holekamp NM, Marsh MJ, Redford M, Schwartz SD, Sternberg P, Thomas MA, Wilson DJ, Anonymous00089. · SST Coordinating Center, Wilmer Clinical Trials and Biometry, 550 North Broadway, 9th Floor, Baltimore, MD 21205-2010, USA. · Ophthalmology. · Pubmed #15522362 links to  free full text

Abstract: PURPOSE: To present visual acuity (VA) and related findings from patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of subfoveal choroidal neovascularization secondary to age-related macular degeneration (SST Group N Trial). DESIGN: Randomized clinical trial. PARTICIPANTS: Eligible patients had age-related macular degeneration with subfoveal choroidal neovascularization, some with a classic pattern on fluorescein angiography, and best-corrected VA (BCVA) of 20/100 to 20/800 in one eye (study eye) that had received no treatment in the macula. Any contiguous blood had to account for <50% of the total area occupied by the subfoveal lesion (maximum size, 9.0 disc areas [22.9 mm2]). METHODS: Randomization was stratified by VA and by clinical center. All patients were scheduled for study examinations at 3, 6, 12, and 24 months after enrollment for assessment of study outcomes. MAIN OUTCOME MEASURE: A successful outcome was defined a priori to be either improvement of BCVA or VA no more than 1 line (7 letters) worse than baseline at the 24-month examination. RESULTS: Of 454 patients enrolled, 228 study eyes were assigned to observation and 226 to surgery. The percentages of eyes that had successful outcomes were similar in the 2 arms: 44% assigned to observation and 41% assigned to surgery. Median VA losses from baseline to the 24-month examination were 2.1 lines (10.5 letters) in the observation arm and 2.0 lines (10 letters) in the surgery arm. Median VA declined from 20/100 at baseline to 20/400 at 24 months in both arms. No subgroup of patients was identified in which submacular surgery led to better VA outcomes. In the surgery arm, 55 (39%) of 142 initially phakic eyes had cataract surgery by the 24-month examination, compared with 6 (5%) of 133 eyes in the observation arm. Rhegmatogenous retinal detachment occurred in 12 surgery eyes (5%) and 1 observation eye. CONCLUSIONS: Submacular surgery, as performed in this clinical trial, did not improve or preserve VA for 24 months in more eyes than observation and is not recommended for patients with similar lesions. This article contains additional online-only material available at http://www.ophsource.com/periodicals/ophtha.

Monson DM, Smith JR, Klein ML, Wilson DJ. · Casey Eye Institute, Portland, OR 97239-4197, USA. · Arch Ophthalmol. · Pubmed #19064845 No free full text.

Abstract: OBJECTIVES: To correlate clinical and histopathologic features of an eye with retinal angiomatous proliferation (RAP) secondary to age-related macular degeneration and to investigate the expression of von Willebrand factor (VWF) and vascular endothelial growth factor (VEGF) in this condition. METHODS: Histopathologic features from serial sections through the globe of an 87-year-old woman with RAP were studied and compared with fluorescein angiography and color fundus photographs obtained 4 months before death. Commercially available anti bodies were used to detect expression of VWF and VEGF in tissue sections. RESULTS: The pathologic correlate of RAP was a circumscribed intraretinal angiomatous complex within the outer part of the neurosensory retina overlying a large pigment epithelial detachment. There were no breaks in the Bruch membrane. No choroidal neovascularization was present. Endothelial cells within the RAP lesion immunostained positively for VWF and VEGF. The Bruch membrane expressed VWF adjacent to the RAP. CONCLUSIONS: Fundus examination and fluorescein angiography images of RAP in a patient with age-related macular degeneration correlated histopathologically with a neovascular intraretinal angiomatous complex, without the presence of sub-retinal pigment epithelial neovascularization. Immunostaining demonstrated that RAP expresses VWF and VEGF.

Anonymous00153, Gilson MM, Bressler NM, Jabs DA, Solomon SD, Thorne JE, Wilson DJ. · Johns Hopkins University, Baltimore, Maryland, USA. · Ophthalmology. · Pubmed #17822977 No free full text.

Abstract: PURPOSE: To evaluate fluorescein angiographic and visual acuity (VA) outcomes from patients enrolled in a trial of a single periocular corticosteroid injection immediately before photodynamic therapy (PDT) versus PDT alone for subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). DESIGN: Randomized 2-center clinical trial. PARTICIPANTS: Sixty-seven subjects with AMD, subfoveal choroidal neovascularization, and best-corrected VA of 20/20 to 20/320 in the study eye who had received no more than 1 prior PDT treatment. METHODS: Subjects were randomized to receive PDT alone (no corticosteroid) or a single periocular corticosteroid injection given via the posterior superior sub-Tenon's capsule route before PDT (corticosteroid) and assessed 1, 3, and 6 months after enrollment. Best-corrected VA and intraocular pressure (IOP) measurements were taken during each examination. Color photographs and fluorescein angiograms were taken at baseline and 3 and 6 months. MAIN OUTCOME MEASURE: Presence or absence of fluorescein leakage from choroidal neovascularization 3 months after randomization. RESULTS: Between the 34 participants randomized to periocular corticosteroid and 33 to no corticosteroid, baseline features appeared balanced. Thirty-three corticosteroid participants and 30 no corticosteroid participants returned for the 3-month follow-up, at which time 56 had fluorescein leakage. Proportions of participants with leakage at 3 months for the 2 treatment groups did not statistically significantly differ; 94% of the corticosteroid group and 90% of the no corticosteroid group had fluorescein leakage at 3 months (P = 0.66). Mean VAs at 3 months after enrollment were 20/100 and 20/125 in the corticosteroid and no corticosteroid groups, respectively, decreasing on average 1.5 and 0.9 lines from baseline (P = 0.50). Adverse events included IOP > 21 mmHg in 7 corticosteroid participants (21%) and 1 (3%) no corticosteroid participant (P<0.05) and ptosis of the study eyelid in 1 (3%) corticosteroid participant. CONCLUSIONS: In contrast to previously reported uncontrolled studies and 1 controlled study, this trial did not find a reduction in the amount of fluorescein leakage 3 months after a single periocular injection of corticosteroid and PDT compared with PDT alone.

Emerson GG, Flaxel CJ, Lauer AK, Stout JT, Emerson MV, Nolte S, Wilson DJ, Klein ML. · Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA. · Retina. · Pubmed #17621181 No free full text.

Abstract: BACKGROUND: To evaluate macular thickness measured by optical coherence tomography (OCT) during pegaptanib therapy for neovascular age-related macular degeneration (AMD). METHODS: For this prospective, nonrandomized, observational case series, 41 eyes from 41 patients with neovascular AMD received intravitreous pegaptanib (1 mg) injections repeated every 6 weeks. The primary outcome measure was central foveal thickness measured by OCT. Secondary outcomes were fluorescein angiographic leakage and visual acuity. RESULTS: Mean thickness of the central area on OCT decreased from 340 +/- 24 microm to 299 +/- 14 microm after 12 weeks of pegaptanib injections. This represents a reduction in thickening of 32%. Fluorescein angiograms with definite leakage decreased from 100% to 81%, and mean visual acuity decreased from 20/116 to 20/120. CONCLUSIONS: Intravitreal injections of pegaptanib at 6-week intervals result in a moderate reduction of central foveal thickness in eyes with subfoveal neovascular AMD. This presents a modest effect relative to that reported with other anti-angiogenic agents.

Emerson MV, Lauer AK, Flaxel CJ, Wilson DJ, Francis PJ, Stout JT, Emerson GG, Schlesinger TK, Nolte SK, Klein ML. · Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA. · Retina. · Pubmed #17420695 No free full text.

Abstract: PURPOSE: To report the change in visual acuity and central retinal thickness by optical coherence tomography (OCT) after intravitreal injections of bevacizumab for the treatment of neovascular age-related macular degeneration (AMD). METHODS: A retrospective case series in a university-based practice evaluated patients with subfoveal choroidal neovascularization (CNV) due to AMD. Patients received intravitreal injections (1.25 mg) of bevacizumab and were monitored monthly with determination of best-corrected ETDRS visual acuity and OCT for persistence of retinal thickening. Eyes were retreated on an "as needed" basis, defined by presence of intraretinal or subretinal fluid. Patients were monitored every 2 months to 3 months for persistence of angiographic leakage. RESULTS: Seventy-nine eyes of 74 consecutive patients received the initial injection of bevacizumab between August 1, 2005, and January 30, 2006. Sixty-eight eyes (86%) of 64 patients had at least 3 months of follow-up. Mean central retinal thickness +/- SD decreased from 304 +/- 83 microm at baseline to 237 +/- 105 microm at 3 months (P = 0.00002). Mean ETDRS visual acuity gained 4 letters from 20/100 at baseline to 20/80-1 at 3 months (P = 0.040). Twenty eyes (25%) appeared to have a sustained response to a single injection and did not require further injections through 3 months. Two patients had a potentially drug-related adverse event (ischemic stroke and myocardial infarction). No serious injection-related adverse events occurred. CONCLUSIONS: Intravitreal bevacizumab injection affects a rapid decrease in retinal thickness to normal or near-normal levels and improvement in visual acuity in eyes with CNV due to AMD. The sustainability of changes in retinal thickness and visual acuity in response to bevacizumab treatment warrant further investigation and long-term follow-up.

Grossniklaus HE, Wilson DJ, Bressler SB, Bressler NM, Toth CA, Green WR, Miskala P. · Department of Ophthalmology, Emory University School of Medicine, 428 Emory Eye Center, 1365 Clifton Road, Atlanta, GA 30322, USA. · Am J Ophthalmol. · Pubmed #16386982 No free full text.

Abstract: PURPOSE: To compare the fundus photographic and fluorescein angiographic features with the histologic findings in eyes from patients enrolled in the Submacular Surgery Trials (SST). DESIGN: Clinical trials with clinicopathologic correlation. METHODS: Eyes that were obtained postmortem from patients who participated in the donor program were processed at the SST Pathology Center and examined histologically; the macular regions were reconstructed topographically with two-dimensional cartography. Fundus photographic and fluorescein angiographic features were correlated with the histopathologic and two-dimensional cartographic findings. RESULTS: The eyes from two patients each from the SST Group N and B Trials were studied. The study eye of one patient that had been assigned randomly to observation contained a subretinal fibrovascular scar that corresponded to a histologic growth pattern of a thick, collagenized subretinal component combined with a subretinal pigment epithelium (subRPE) fibrovascular component. The study eye of the other patient who was assigned randomly to observation showed angiographic occult without classic choroidal neovascularization (CNV) that corresponded to subRPE CNV. The study eye of one patient who was assigned randomly to surgery showed an angiographic surgical defect without CNV and histologic retinal pigment epithelium (RPE)/photoreceptor atrophy that was associated with a thin layer of subRPE CNV. The study eye of the other patient who was assigned randomly to surgery showed an angiographic surgical defect with classic CNV that corresponded to histologic RPE/photoreceptor atrophy that was associated with subRPE fibrovascular tissue and subretinal CNV. Both surgical eyes contained linear breaks in Bruch's membrane that included chevron-shaped breaks. CONCLUSION: Four SST study eyes that were examined postmortem contained CNV. The angiographic patterns and histologic features of the CNV support previous correlations of surgically excised CNV.

Grossniklaus HE, Miskala PH, Green WR, Bressler SB, Hawkins BS, Toth C, Wilson DJ, Bressler NM. · Montgomery Ophthalmic Pathology Labotratory, BT0428 Emory Eye Center, 1365 Clifton Road NE, Atlanta, GA 30322, USA. · Arch Ophthalmol. · Pubmed #16009831 No free full text.

Abstract: OBJECTIVES: To identify the histologic and ultrastructural features of surgically excised subfoveal choroidal neovascular lesions from patients enrolled in the Submacular Surgery Trials and to compare them with clinical data. METHODS: Surgically excised subfoveal choroidal neovascular lesions from patients enrolled in the Submacular Surgery Trials group N trial (lesion predominantly choroidal neovascularization [CNV] with evidence of classic CNV from age-related macular degeneration), group B trial (lesion predominantly hemorrhagic from age-related macular degeneration), and group H trial (idiopathic subfoveal CNV or subfoveal CNV from ocular histoplasmosis syndrome) between October 1, 1999, and September 1, 2001, were submitted to the pathology center. The lesion growth pattern (subretinal pigment epithelial [sub-RPE], subretinal, combined, or indeterminate) and the cellular and extracellular constituents were classified independently. Demographic, clinical, and fluorescein angiographic characteristics of patients, eyes, and lesions, respectively, were compared with the pathologic features. RESULTS: Of 269 patients assigned to surgery during the 24 months that pathologic specimens were collected, surgical specimens from study eyes of 199 were submitted to the pathology center. Of the 199 routine histologic specimens processed, 144 (72%) were classified as CNV, 51 (26%) as fibrocellular tissue, and 4 (2%) as hemorrhage. The median specimen size was smaller in group H (932 x 208 mum) than in groups N (1980 x 325 mum) and B (1800 x 395 mum). The CNV growth pattern was determined in 91 (46%) of 199 specimens. Of 159 group N and group B lesions, 76 (48%) had an indeterminate growth pattern, 28 (18%) had a sub-RPE growth pattern, and 33 (21%) had sub-RPE and subretinal growth patterns. Of 40 group H lesions, 32 (80%) had an indeterminate growth pattern, 7 (18%) had a subretinal growth pattern, and 1 (2%) had a combined sub-RPE and subretinal pattern. Based on electron microscopy, the most common cellular lesion components were RPE, macrophages, erythrocytes, fibrocytes, and vascular endothelium; the most common extracellular components were 24-nm collagen and fibrin. Basal laminar and linear deposits were found in 80% (40/50) and 16% (8/49) of group N specimens, 66% (43/65) and 5% (3/65) of group B specimens, and 8% (2/26) and 0% (0/26) of group H specimens, respectively. CONCLUSIONS: Most surgically excised subfoveal specimens had evidence of CNV or tissue associated with CNV. The constituents in CNV were consistent with granulation tissue proliferation. The presence of basal deposits in surgically excised specimens suggested a clinical diagnosis of age-related macular degeneration, even when blood was the predominant component of the lesion. Correlation of growth patterns above or below the RPE with fluorescein angiographic patterns of classic or occult CNV was limited because most specimens had insufficient material to determine these patterns.

Lauer AK, Yoken J, Klein ML, Wilson DJ. · Casey Eye Institute, Oregon Health and Science University, 3575 SW Terwilliger Boulevard, Portland, OR 97239, USA. · Arch Ophthalmol. · Pubmed #15364723 No free full text.

This publication has no abstract.

Lauer AK, Wilson DJ, Klein ML. · Macular Degeneration Center and Leonard Christenen Eye Pathology Laboratory, Casey Eye Institute, Oregon Health Sciences University, Portland 97201-4197, USA. · Retina. · Pubmed #11039424 No free full text.

Abstract: PURPOSE: To correlate the clinical and histopathologic features of an eye with age-related macular degeneration studied with fluorescein (FA) and indocyanine green (ICG) angiography 4.5 months before the patient's death. METHODS: Histopathologic features from serial sections through the macula of a 76-year-old man with occult choroidal neovascularization (CNV) were reconstructed in a scaled two-dimensional map and compared with FA and ICG angiogram images obtained 4.5 months before his death. RESULTS: The region of prior laser photocoagulation was identified as a well-demarcated hypofluorescent region in the early frames of the FA and the early and late phases of the ICG angiogram. This corresponded histopathologically to a well-circumscribed area of absence of the choriocapillaris, loss of the outer retina and retinal pigment epithelium, and scarring of the choroid. Occult CNV characterized by elevated late hyperfluorescence on the FA and intense well-defined hyperfluorescence on the ICG angiogram corresponded to a thick fibrovascular membrane in the subretinal space and within Bruch's membrane. Thin extensions of both the subretinal and intra-Bruch's membrane fibrovascular membrane components corresponded to nonelevated stippled late hyperfluorescence on the FA and mild late hyperfluorescence on the ICG angiogram. CONCLUSION: Histopathologic mapping revealed a large fibrovascular complex located subretinally and within Bruch's membrane with thin and thick components that correlate well with findings of occult CNV on FA and ICG angiography.