Macular Degeneration: Bressler SB

Chang MA, Fine HF, Bass E, Bressler SB, Schachat AP, Solomon SD, Bressler NM. · Department of Ophthalmology, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Retina. · Pubmed #17621191 No free full text.

Abstract: PURPOSE: The purpose of this study was to assess preference values for vein occlusions with macular edema and to determine how this may affect patient perceptions of potential treatments. METHODS: The Submacular Surgery Trials Vision Preference Value Scale and questions regarding enthusiasm for potential treatments were administered to 153 patients with vein occlusion. Univariate analyses identified predictors of preference values, followed by adjustment for potential confounders using multivariate linear regression. Relationships between preference values and enthusiasm for potential treatments were assessed. RESULTS: The mean preference values +/- SD were similar for patients with branch vein occlusions and central vein occlusions (0.65 +/- 0.20). Lower preference values were associated with duration of occlusion of >2 years (P=0.03) and poorer last-recorded visual acuity (P=0.02). Approximately one half of patients were moderately or very enthusiastic about undergoing intravitreal injection. Sixty-nine percent of branch vein occlusion patients were moderately or very enthusiastic about the standard of care, laser photocoagulation; only one third of central vein occlusion patients were moderately or very enthusiastic about standard observation. CONCLUSIONS: These data suggest that vein occlusion with macular edema has a significant impact on quality of life. Most patients were willing to undergo potentially invasive treatment.

Anonymous00228, Mann AL, Bressler SB, Hawkins BS, Holekamp N, Bressler NM. · Submacular Surgery Trials Chair's Office, Wilmer Eye Institute, Johns Hopkins University, 550 North Broadway, Suite 115, Baltimore, MD 21205, USA. · Ophthalmology. · Pubmed #17574675 No free full text.

Abstract: PURPOSE: To describe and compare methods used to monitor development and progression of presumed vision-limiting lens opacity in study eyes of Submacular Surgery Trials (SST) patients. DESIGN: Prospective study of patients enrolled in a set of randomized clinical trials. PARTICIPANTS: Patients enrolled in the SST who were phakic in the study eye at the time of enrollment (n = 690). In a subset of 114 patients, lens photographs were obtained at baseline and 2 years after enrollment. METHODS: Data collection at baseline and annual follow-up examinations included ocular history, ophthalmologic examination including the SST ophthalmologist's assessment of presence or absence of vision-limiting opacity, fundus photography, and lens photography (13 of 27 clinics only). All photographs were assessed by masked graders centrally using the Lens Opacities Classification System III (LOCS III). kappa statistics were calculated to compare LOCS III cataract classifications with fundus photograph quality and with the ophthalmologist's assessment of lens opacity, with the LOCS III classification considered the gold standard. MAIN OUTCOME MEASURE: Incidence of cataract in study eyes. RESULTS: Baseline lens photographs were available and graded for 312 (45%) of 690 patients with phakic study eyes; 2-year lens photographs were available for 156 (23%) of 690 initially phakic eyes. Both baseline and 2-year lens photographs were available for 114 eyes that remained phakic. Submacular surgery was associated with significant progression of nuclear color and nuclear opalescence characteristics within 2 years of enrollment. The reliability of fundus photograph quality versus cataract classification using a 4.5 LOCS III score threshold for cataract was poor to good at each time point and for all groups (kappa, 0-0.51), but sensitivity of the photograph quality score as a surrogate was low, and both positive and negative predictive values were low. Agreement between the ophthalmologists' assessments of lens opacity and the 4.5 LOCS III score threshold for cataract was good (kappa, 0.42-0.78). CONCLUSIONS: In the SST, clinical identification of severe cataract (LOCS III scores of 4.5 or worse for nuclear opacity or nuclear color) by the examining ophthalmologist was valid based on comparison with LOCS III scores and may be an adequate method to use in similar trials.

Pieramici DJ, Bressler SB, Koester JM, Bressler NM. · No affiliation provided · Arch Ophthalmol. · Pubmed #16682587 links to  free full text

Abstract: OBJECTIVE: To determine whether data from patients with age-related macular degeneration (AMD) assigned to the placebo group in the Verteporfin in Photodynamic Therapy (VIP) Trial provide a rationale for continuation or cessation of follow-up of individuals with subfoveal occult choroidal neovascularization (CNV) with no classic lesions, presumed recent disease progression, larger lesion size (>4 disc areas), and a higher level of visual acuity (approximate Snellen equivalent, > or =20/50 in the affected eye) in whom no treatment is given at initial examination. METHODS: In a prospective, noncomparative case series, angiograms of participants assigned to a placebo group who had occult with no classic lesion composition at baseline were reviewed to identify conversion to minimally classic (area of classic CNV >0% but <50% of the entire lesion area) or predominantly classic (area of classic CNV > or =50% of the entire lesion area) composition. RESULTS: Of the 114 patients with AMD assigned to the placebo group, 89 were judged to have occult with no classic lesion composition at baseline in the study eye when fluorescein angiograms were reviewed in late 2001 for this report. By 24 months, 7 (8%) of the 89 patients had lesions that converted to predominantly classic composition, and 41 (46%) had minimally classic composition. Among the 24 patients with a baseline visual acuity better than 20/50(-1) and lesion size greater than 4 disc areas whose lesions did not convert to predominantly classic composition, the visual acuity of 18 (75%) dropped below 20/50. Six of these 18 continued to have occult with no classic CNV with a visual acuity of 20/100 or better and had a lesion size no greater than 9 disc areas at the time that visual acuity dropped below 20/50. CONCLUSIONS: Continued monitoring, rather than cessation of follow-up, is recommended for patients with occult with no classic lesions, similar to those patients enrolled in the VIP Trial who did not initially receive treatment when they had relatively large lesions with good visual acuity. In these cases, if visual acuity decreases or predominantly classic features develop, photodynamic therapy with verteporfin or pegaptanib sodium injections may be considered.

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.

Ferris FL, Davis MD, Clemons TE, Lee LY, Chew EY, Lindblad AS, Milton RC, Bressler SB, Klein R, Anonymous00307. · AREDS Coordinating Center, The EMMES Corporation, Rockville, MD 20850-1707, USA. · Arch Ophthalmol. · Pubmed #16286620 links to  free full text

Abstract: OBJECTIVE: To develop a simplified clinical scale defining risk categories for development of advanced age-related macular degeneration (AMD). METHODS: Following development of a detailed scale for individual eyes based on gradings of fundus photographs in the Age-Related Eye Disease Study, rates of progression to advanced AMD were assessed in cross-tabulations of presence or absence in each eye of 2 easily identified retinal abnormalities, drusen and pigment abnormalities. Large drusen and any pigment changes were particularly predictive of developing advanced AMD. RESULTS: The scoring system developed for patients assigns to each eye 1 risk factor for the presence of 1 or more large (> or = 125 microm, width of a large vein at disc margin) drusen and 1 risk factor for the presence of any pigment abnormality. Risk factors are summed across both eyes, yielding a 5-step scale (0-4) on which the approximate 5-year risk of developing advanced AMD in at least one eye increases in this easily remembered sequence: 0 factors, 0.5%; 1 factor, 3%; 2 factors, 12%; 3 factors, 25%; and 4 factors, 50%. For persons with no large drusen, presence of intermediate drusen in both eyes is counted as 1 risk factor. CONCLUSION: This simplified scale provides convenient risk categories for development of advanced AMD that can be determined by clinical examination or by less demanding photographic procedures than used in the Age-Related Eye Disease Study.

Davis MD, Gangnon RE, Lee LY, Hubbard LD, Klein BE, Klein R, Ferris FL, Bressler SB, Milton RC, Anonymous00306. · AREDS Coordinating Center, EMMES Corp, Rockville, MD 20850-1707, USA. · Arch Ophthalmol. · Pubmed #16286610 links to  free full text

Abstract: OBJECTIVE: To develop a fundus photographic severity scale for age-related macular degeneration (AMD). METHODS: In the Age-Related Eye Disease Study, stereoscopic color fundus photographs were taken at baseline, at the 2-year follow-up visit, and annually thereafter. Photographs were graded for drusen characteristics (size, type, area), pigmentary abnormalities (increased pigment, depigmentation, geographic atrophy), and presence of abnormalities characteristic of neovascular AMD (retinal pigment epithelial detachment, serous or hemorrhagic sensory retinal detachment, subretinal or sub-retinal pigment epithelial hemorrhage, subretinal fibrous tissue). Advanced AMD was defined as presence of 1 or more neovascular AMD abnormalities, photocoagulation for AMD, or geographic atrophy involving the center of the macula. We explored associations among right eyes of 3212 participants between severity of drusen characteristics and pigmentary abnormalities at baseline and development of advanced AMD within 5 years of follow-up. RESULTS: A 9-step severity scale that combines a 6-step drusen area scale with a 5-step pigmentary abnormality scale was developed, on which the 5-year risk of advanced AMD increased progressively from less than 1% in step 1 to about 50% in step 9. Among the 334 eyes that had at least a 3-step progression on the scale between the baseline and 5-year visits, almost half showed stepwise progression through intervening severity levels at intervening visits. Replicate gradings showed agreement within 1 step on the scale in 87% of eyes. CONCLUSIONS: The scale provides convenient risk categories and has acceptable reproducibility. Progression along it may prove to be useful as a surrogate for progression to advanced AMD.

Alster Y, Bressler NM, Bressler SB, Brimacombe JA, Crompton RM, Duh YJ, Gabel VP, Heier JS, Ip MS, Loewenstein A, Packo KH, Stur M, Toaff T, Anonymous00244. · Clin Reg Consulting Services Inc., Irvine, California, USA. · Ophthalmology. · Pubmed #16154198 No free full text.

Abstract: PURPOSE: To assess the ability of the Preferential Hyperacuity Perimeter (PreView PHP; Carl Zeiss Meditec, Dublin, CA) to detect recent-onset choroidal neovascularization (CNV) resulting from age-related macular degeneration (AMD) and to differentiate it from an intermediate stage of AMD. DESIGN: Prospective, comparative, concurrent, nonrandomized, multicenter study. PARTICIPANTS: Eligible participants' study eyes had a corrected visual acuity of 20/160 or better and either untreated CNV from AMD diagnosed within the last 60 days or an intermediate stage of AMD. METHODS: After obtaining consent, visual acuity with habitual correction, masked PHP testing, stereoscopic color fundus photography, and fluorescein angiography were performed. Photographs and angiograms were evaluated by graders masked to diagnosis and PHP results. The reading center's diagnosis determined if the patient was categorized as having intermediate AMD or neovascular AMD. MAIN OUTCOME MEASURES: A successful study outcome was defined a priori as a sensitivity of at least 80% and a specificity of at least 80%. RESULTS: Of 185 patients who gave consent to be enrolled, 11 (6%) had PHP results judged to be unreliable. An additional 52 were not included because they did not meet all eligibility criteria. Of the remaining 122 patients, 57 had an intermediate stage of AMD and 65 had neovascular AMD. The sensitivity to detect newly diagnosed CNV using PHP testing was 82% (95% confidence interval [CI], 70%-90%). The specificity to differentiate newly diagnosed CNV from the intermediate stage of AMD using PHP testing was 88% (95% CI, 76%-95%). CONCLUSIONS: Preferential Hyperacuity Perimeter testing can detect recent-onset CNV resulting from AMD and can differentiate it from an intermediate stage of AMD with high sensitivity and specificity. These data suggest that monitoring with PHP should detect most cases of CNV of recent onset with few false-positive results at a stage when treatment usually would be beneficial. Thus, this monitoring should be considered in the management of the intermediate stage of AMD.

Bressler SB, Silva JC, Bressler NM, Alexander J, Green WR. · No affiliation provided · Retina. · Pubmed #16049367 No free full text.

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Bressler NM, Silva JC, Bressler SB, Fine SL, Green WR. · No affiliation provided · Retina. · Pubmed #16049360 No free full text.

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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.

Freeman EE, Muñoz B, Bressler SB, West SK. · Dana Center for Preventive Ophthalmology, Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, MD 21287, USA. · Ophthalmic Epidemiol. · Pubmed #15848919 No free full text.

Abstract: PURPOSE: To evaluate a potential relationship between hormone replacement therapy (HRT), reproductive factors and age-related macular degeneration (AMD). METHODS: 1,458 female participants (age 65-84) from the Salisbury Eye Evaluation study were available for this cross-sectional analysis. AMD outcomes were identified by reading center assessment of fundus photographs. RESULTS: Women who currently used HRT had a lower adjusted odds of large drusen (> 125 microm) (OR = 0.5, 95% CI 0.2-1.0). Use of HRT was not statistically significantly associated with the prevalence of early AMD or advanced AMD, although the odds ratios were all much less than 1. Women who had had an increased number of births had a greater prevalence of large drusen (test of linear trend, p = 0.03). CONCLUSIONS: Current use of HRT was associated with a lower odds of large drusen, which may be predictive of advanced AMD. No statistically significant correlations were found between HRT or reproductive factors and early or advanced AMD.

Sadda SR, Pieramici DJ, Marsh MJ, Bressler NM, Bressler SB, Anonymous00372. · Doheny Retina Institute, Doheny Eye Institute, Los Angeles, California, USA. · Retina. · Pubmed #15579986 No free full text.

Abstract: PURPOSE: To compare the size of subfoveal lesions based on photographic documentation before and after submacular surgery of choroidal neovascularization (CNV) lesions. METHODS: Subfoveal lesion sizes at baseline and month 3 follow-up visits for patients assigned to surgery in the Submacular Surgery Trials (SST) Pilot Study were assessed categorically using Macular Photocoagulation Study (MPS) disc area (DA) circles. The Submacular Surgery Trials Pilot Study groups reviewed were as follows: Group N (age-related macular degeneration [AMD]; lesion <50% blood; classic CNV present; size < or =9 MPS DAs); Group R (AMD; prior nonfoveal laser; classic CNV present; size < or =9 MPS DAs); Group B (AMD; lesion > or =50% blood); and Group H (ocular histoplasmosis syndrome or idiopathic; classic CNV present; size < or =9 MPS DAs). RESULTS: Postoperative month 3 lesion size was at least 1 size category smaller than the preoperative lesion size in 6% (4/66) of Group N, 0 (0/31) of Group R, 6% (2/34) of Group H, and 45% (18/40) of Group B eyes. In Group H eyes, there was no size change in 50% (17/34), and enlargement was found in 44% (15/34). For eyes in Groups N and R, approximately one third remained stable (20/66, 30% and 12/31, 39%, respectively), whereas two thirds enlarged by at least 1 category (42/66, 64% and 19/31, 61%, respectively). CONCLUSIONS: The change in lesion size after submacular surgery was variable, with a tendency for Group H lesions to remain the same size or larger, Group B lesions to measure smaller, and Group N and Group R lesions to be larger.

Azab M, Benchaboune M, Blinder KJ, Bressler NM, Bressler SB, Gragoudas ES, Fish GE, Hao Y, Haynes L, Lim JI, Menchini U, Miller JW, Mones J, Potter MJ, Reaves A, Rosenfeld PJ, Strong A, Su XY, Slakter JS, Schmidt-Erfurth U, Sorenson JA, Anonymous00093, Anonymous00094. · No affiliation provided · Retina. · Pubmed #15076937 No free full text.

Abstract: PURPOSE: We sought to evaluate the detailed safety profile of photodynamic therapy with verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (ARMD) from the combined analysis of three multicenter, double-masked, placebo-controlled, randomized 24-month clinical trials of similar design (TAP Investigation Studies A and B and the VIP ARMD Trial), and to clarify the adverse reaction information in the current verteporfin product prescription information approved in the United States. METHODS: Nine hundred forty-eight patients were randomly assigned to verteporfin or placebo. Treatment was administered as described in previous reports. All general entry criteria were similar, so systemic safety results were combined for this analysis. Entry criteria for CNV lesion composition and visual acuity in the two TAP Investigation trials was different from those used in the VIP ARMD trial, so ocular safety results for the treated eye were not combined. RESULTS: The percentage of patients who experienced at least one ocular or nonocular adverse event, regardless of relationship to therapy, was similar between the verteporfin and placebo groups (92.3 and 89.1%, respectively, P = 0.114). The overall incidence of study eye adverse events was not significantly different between verteporfin and placebo. The only clinically relevant ocular adverse events reported with higher incidence after verteporfin compared with placebo were visual disturbances (22.1 versus 15.5% in TAP [P = 0.054] and 41.7 and 22.8% in VIP [P < 0.001]). Acute severe visual acuity decrease (defined as a visual acuity letter score decrease of at least 20, equivalent to at least four-line decrease, within 7 days of therapy) occurred in 3 patients treated with verteporfin in the TAP Investigation (0.7%) and 11 in the VIP ARMD trial (4.9%). Systemic adverse events with increased incidence after verteporfin compared with placebo, most of which were transient and mild or moderate, were injection site reactions (13.1 versus 5.6%; P < 0.001), photosensitivity reactions (2.4 versus 0.3%; P = 0.016), and infusion-related back pain (2.4 versus 0%; P = 0.004). No clinically relevant difference was observed between the verteporfin and placebo groups in any other adverse event. CONCLUSION: In 948 ARMD patients, verteporfin therapy had an overall safety profile similar to that for placebo, with a few exceptions. Visual disturbances, including acute severe visual acuity decrease, did not affect the net vision outcome benefits associated with treatment that has been reported previously. This detailed safety profile of verteporfin therapy clarifies the adverse reaction information in the current verteporfin product prescription information.

Arnold JJ, Blinder KJ, Bressler NM, Bressler SB, Burdan A, Haynes L, Lim JI, Miller JW, Potter MJ, Reaves A, Rosenfeld PJ, Sickenberg M, Slakter JS, Soubrane G, Strong HA, Stur M, Anonymous00242, Anonymous00243. · No affiliation provided · Am J Ophthalmol. · Pubmed #15059708 No free full text.

Abstract: PURPOSE: To describe in detail occurrences of acute severe visual acuity decrease after photodynamic therapy (PDT) with verteporfin in the Treatment of Age-related macular degeneration with Photodynamic therapy (TAP) Investigation and the Verteporfin In Photodynamic therapy (VIP) Trial. DESIGN: Observational case series. METHODS: Retrospective review of all cases that developed acute severe visual acuity decrease after treatment. RESULTS: Of 15 acute severe visual acuity decrease events originally identified in 14 eyes of 14 patients, one event in one patient was judged unlikely to have been an acute severe visual acuity decrease event on retrospective review of these events in preparation of this report. Eleven events occurred after the first treatment. At follow-up, 10 improved by at least 1 line in visual acuity from the level noted at the time of the event. Of the nine patients returning for the month 24 examination, visual acuity decreased at least 3 lines from baseline in six, including at least 6 lines in four, and remained within 1 line in three. Associated abnormal morphology included three with a serous macular detachment and abnormal choroidal hypofluorescence, four with macular hemorrhage, three with a greenish subfoveal hemorrhage, and four with no abnormality. Events appeared to be more likely when patients had a visual acuity of 20/50 or better. CONCLUSIONS: Acute severe visual acuity decrease after PDT with verteporfin was an uncommon event; the risk did not outweigh the benefits of therapy previously reported. When considering verteporfin therapy, patients should be warned of the possibility of this serious adverse event.

Do DV, Bressler NM, Bressler SB. · The Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. · Am J Ophthalmol. · Pubmed #15013883 No free full text.

Abstract: PURPOSE: To report the occurrence of large submacular hemorrhages after photodynamic therapy with verteporfin in age-related macular degeneration patients with subfoveal choroidal neovascularization (CNV) composed of occult with no classic CNV in whom the hemorrhage precluded determining if additional therapy should be given within 3 months after initiation of treatment. DESIGN: Retrospective, noncomparative case series. METHODS: The records of all age-related macular degeneration patients who received verteporfin therapy for subfoveal lesions composed of occult with no classic CNV between February and July 2001 at The Wilmer Eye Institute were reviewed. Subjects who reported either having undergone a procedure to remove intraocular blood before a month 3 follow-up visit, or who had submacular hemorrhage at the month 3 visit that was severe enough to preclude determining if additional verteporfin therapy should be given were identified. RESULTS: Fifty-five eyes of 52 patients were reviewed. Five eyes (9% [95% confidence interval, 1.4%-16.6%]) developed submacular hemorrhage that precluded determining if additional verteporfin therapy should be given. Visual acuity 3 months after documentation of the hemorrhage decreased a median of 8.5 lines compared with pretreatment acuity. CONCLUSIONS: Even in the absence of acute severe visual acuity decrease, submacular hemorrhage after verteporfin therapy can be associated with severe vision loss and preclude determining if additional therapy should be given.

Brown JC, Solomon SD, Bressler SB, Schachat AP, DiBernardo C, Bressler NM. · Retinal Vascular Center, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2002, USA. · Arch Ophthalmol. · Pubmed #15006844 No free full text.

Abstract: OBJECTIVE: To compare contact lens biomicroscopy with optical coherence tomography (OCT) for the detection of diabetic foveal edema. METHODS: Study participants consisted of a convenient cohort of consecutive patients with diabetes mellitus seen at the Wilmer Eye Institute's Retinal Vascular Center, Baltimore, MD. Case characteristics were recorded and eyes were examined by 1 of 4 retina specialists by means of contact lens biomicroscopy. Edema involving the center of the macula was assessed as definitely present, questionably present, or definitely not present. The OCT testing was performed and interpreted by trained technicians, masked to the physicians' assessment of foveal edema. Agreement between OCT and contact lens examination for the absence or presence of foveal edema was evaluated. RESULTS: One hundred seventy-two eyes of 95 patients with diabetes were enrolled in August and September 2002. Foveal thickness was objectively measured by OCT in 170 (99%) of 172 cases. We found excellent agreement between OCT and contact lens examination for the absence or presence of foveal edema when OCT thickness was normal (<or=200 microm) or moderately to severely increased (>300 microm). However, agreement was poor when foveal thickness was mildly increased on OCT (201-300 microm). CONCLUSIONS: Agreement between contact lens examination and OCT for the detection of diabetic foveal edema is poor when OCT thickening is mild. This suggests that contact lens biomicroscopy is relatively insensitive for the detection of mild foveal thickening apparent on OCT. Additional studies are needed to investigate the natural course of cases with mildly increased foveal thickness on OCT that do not appear thickened clinically.

Bressler SB, Pieramici DJ, Koester JM, Bressler NM. · Department of Ophthalmology, The Johns Hopkins University School of Medicine and The Johns Hopkins Hospital, Baltimore, MD 20205-2002, USA. · Arch Ophthalmol. · Pubmed #15006843 No free full text.

Abstract: OBJECTIVE: To determine if there is a rationale for monitoring patients with age-related macular degeneration who have a minimally classic subfoveal choroidal neovascular lesion and do not receive treatment at initial examination. METHODS: Participants assigned to placebo who had a minimally classic lesion composition at baseline were identified from the TAP Investigation. Fluorescein angiograms at baseline and follow-up examinations from these participants were reviewed by photograph reading center graders to determine if any follow-up angiograms had converted from a minimally classic lesion composition to a predominantly classic lesion composition. MAIN OUTCOME MEASURES: Proportion of minimally classic lesions at baseline that converted to a predominantly classic lesion composition, time of this conversion, and visual acuity and lesion size at the time of conversion. RESULTS: Of the 207 patients assigned to placebo in the TAP Investigation, 98 were judged to have a minimally classic lesion at baseline in the study eye when the fluorescein angiograms were reviewed in 2001. Of these 98 patients, 39 (40%) had lesions that converted to a predominantly classic lesion composition, including 21 by the month 3 examination. At the time of conversion, 32 (82%) lesions were no greater than 9 disc areas, including 20 (51%) with visual acuity of 20/200 or better. CONCLUSIONS: These data would suggest that patients with minimally classic lesions, in whom no therapy is recommended initially, should be monitored so that potential conversion to a predominantly classic lesion can be identified promptly and verteporfin therapy considered.

Bressler NM, Bressler SB, Congdon NG, Ferris FL, Friedman DS, Klein R, Lindblad AS, Milton RC, Seddon JM, Anonymous00184. · No affiliation provided · Arch Ophthalmol. · Pubmed #14609922 links to  free full text

Abstract: OBJECTIVE: To estimate the potential public health impact of the findings of the Age-Related Eye Disease Study (AREDS) on reducing the number of persons developing advanced age-related macular degeneration (AMD) during the next 5 years in the United States. METHODS: The AREDS clinical trial provides estimates of AMD progression rates and of reduction in risk of developing advanced AMD when a high-dose nutritional supplement of antioxidants and zinc is used. These results are applied to estimates of the US population at risk, to estimate the number of people who would potentially avoid advanced AMD during 5 years if those at risk were to take a supplement such as that used in AREDS. RESULTS: An estimated 8 million persons at least 55 years old in the United States have monocular or binocular intermediate AMD or monocular advanced AMD. They are considered to be at high risk for advanced AMD and are those for whom the AREDS formulation should be considered. Of these people, 1.3 million would develop advanced AMD if no treatment were given to reduce their risk. If all of these people at risk received supplements such as those used in AREDS, more than 300,000 (95% confidence interval, 158,000-487,000) of them would avoid advanced AMD and any associated vision loss during the next 5 years. CONCLUSION: If people at high risk for advanced AMD received supplements such as those suggested by AREDS results, the potential impact on public health in the United States would be considerable during the next 5 years.

Blinder KJ, Bradley S, Bressler NM, Bressler SB, Donati G, Hao Y, Ma C, Menchini U, Miller J, Potter MJ, Pournaras C, Reaves A, Rosenfeld PJ, Strong HA, Stur M, Su XY, Virgili G, Anonymous00153, Anonymous00154. · · Am J Ophthalmol. · Pubmed #12967792 No free full text.

Abstract: PURPOSE: To determine whether differences in baseline lesion size and visual acuity might explain differing results found in three different lesion compositions (predominantly classic, minimally classic, and occult with no classic) among three placebo-controlled, randomized clinical trials evaluating photodynamic therapy with verteporfin (Visudyne, Novartis AG), also termed verteporfin therapy, in patients with subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHODS: Exploratory analyses were conducted in patients with predominantly classic or minimally classic lesions at enrollment in the Treatment of AMD with Photodynamic Therapy (TAP) Investigation and in AMD patients with occult with no classic CNV in the Verteporfin In Photodynamic Therapy (VIP) Trial. Baseline characteristics of patients among these three lesion compositions were compared. In addition, multiple linear regression modeling was used to explore the effect of baseline lesion size, visual acuity, and lesion composition on mean change in visual acuity from baseline to 24 months. RESULTS: At baseline, the mean size of predominantly classic lesions (3.4 disk areas) was smaller than that of minimally classic (4.7 disk areas) and occult with no classic lesions (4.3 disk areas). In the multiple linear regression model of individual lesion compositions, there was a significant treatment-by-lesion-size interaction for minimally classic and occult with no classic lesions, but not for predominantly classic lesions. Interaction between treatment and baseline visual acuity was not significant for any lesion composition. Small verteporfin-treated lesions lost less vision than large verteporfin-treated lesions in each lesion composition. In the multiple linear regression model that included all lesion compositions, lesion size was a more significant predictive factor for the magnitude of treatment benefit than either lesion composition or visual acuity. Smaller (4.0 disk areas or less) minimally classic and occult with no classic lesions had similar visual acuity outcomes to those observed in predominantly classic lesions. CONCLUSIONS: Based on exploratory analyses, lesion size in the TAP Investigation and VIP Trial was an important predictor of the magnitude of treatment benefit with verteporfin therapy in occult with no classic and minimally classic lesion compositions. In patients with AMD, treating smaller rather than larger neovascular lesions, regardless of lesion composition, likely will result in a better level of visual acuity.

Barbazetto I, Burdan A, Bressler NM, Bressler SB, Haynes L, Kapetanios AD, Lukas J, Olsen K, Potter M, Reaves A, Rosenfeld P, Schachat AP, Strong HA, Wenkstern A, Anonymous00097, Anonymous00098. · Medizinische Universität zu Lübeck, Klinik für Augenheilkunde, Lübeck, Germany. · Arch Ophthalmol. · Pubmed #12963608 No free full text.

Abstract: OBJECTIVE: To describe fluorescein angiographic guidelines for the use of verteporfin therapy in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) or other conditions based on 2-year vision outcomes from the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) Investigation and Verteporfin in Photodynamic Therapy (VIP) Trial. METHODS: Three multicenter, double-masked, placebo-controlled randomized clinical trials at 28 ophthalmology clinical centers in Europe and North America involving prospectively identified patients with best-corrected visual acuity (Snellen equivalent) of approximately 20/20 to 20/200, subfoveal CNV secondary to AMD or pathologic myopia with evidence of CNV, and a lesion greatest linear dimension of 5400 micro m or less. Fluorescein angiography was to be performed on all patients at enrollment and at regular 3-month follow-up visits through 2 years. The initial treatment laser spot size and all subsequent treatment decisions were based on the investigator's interpretation of these fluorescein angiograms. Photographic materials forwarded to the Wilmer Photograph Reading Center were reviewed by masked graders. MAIN OUTCOME MEASURES: Baseline angiographic features, including lesion composition and size, morphologic response to treatment during follow-up (eg, absence of leakage), and reliability (kappa values) of grading selected characteristics based on a 10% regrading of baseline visits. RESULTS: Terms and examples of different lesions and lesion components are provided to assist recognition of fluorescein angiographic characteristics of choroidal neovascular lesions that were important in determining when and where to apply verteporfin therapy. The kappa statistics for agreement of identification of lesion characteristics by the Wilmer Photograph Reading Center for these trials ranged from 0.70 to 0.85. CONCLUSIONS: Ophthalmologists should consider interpreting fluorescein angiographic images of subfoveal lesions with terms provided to follow recommendations regarding which patients are most likely to benefit from verteporfin therapy based on results from the TAP Investigation and VIP Trial.

Ladd BS, Solomon SD, Bressler NM, Bressler SB. · Retinal Vascular Center, Wilmer Ophthalmological Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine and Hospital, Baltimore, Maryland, USA. · Am J Ophthalmol. · Pubmed #11704027 No free full text.

Abstract: PURPOSE: To report the use of photodynamic therapy (PDT) with verteporfin in three patients with choroidal neovascularization (CNV) from age-related macular degeneration and underlying diabetic retinopathy. The level of diabetic retinopathy would have excluded these patients from participation in previously reported randomized clinical trials evaluating PDT with verteporfin due to a theoretic concern of damage to the overlying retinal vasculature. DESIGN: Retrospective interventional case series. METHODS: Three patients from a referral practice with at least severe nonproliferative diabetic retinopathy and a history of clinically significant macular edema developed loss of vision from concurrent choroidal neovascularization evaluated with fundus photography and fluorescein angiography before and after PDT with verteporfin to identify adverse retinal vascular events. RESULTS: Four eyes in three patients had PDT using verteporfin. Three eyes received two treatments. With short follow-up, visual acuity remained stable in two eyes, improved from 20/400 to 20/320 in one eye, and decreased from 20/200 to 20/400 in one eye. Fluorescein angiograms at intervals from 2 weeks to 3 months after PDT showed no damage to the retinal vasculature or progression of the diabetic retinopathy, but did show a decreased area of fluorescein leakage from CNV. One eye that had new subretinal hemorrhage following treatment appeared to show new vasculopathy on initial evaluation of the post-treatment angiogram. Retrospective review suggested that the subretinal hemorrhage provided increased contrast to more easily visualize vasculopathy that was present before the PDT. CONCLUSIONS: Three patients with diabetic retinopathy undergoing a total of seven PDT treatments with verteporfin in four eyes had no new retinal vascular abnormalities develop. No other atypical responses of CNV to PDT were noted except new subretinal hemorrhage, providing increased contrast of the overlying vasculature, which gave the false impression of the development of new vasculopathy in one eye. Patients with diabetic retinopathy who have concurrent CNV for which PDT with verteporfin is recommended should be cautioned regarding the theoretical concerns of harming the retinal vasculature. Periodic surveillance for such concerns seems warranted until more experience is obtained.

Anand R, Bressler NM, Bressler SB, Gray TE, Harvey P, Haynes L, Koester JM, Manos KS, Miller JW, Murphy S, Reaves A, Sickenberg M, Singerman LJ, Strong A, Stur M, Anonymous00416. · No affiliation provided · Arch Ophthalmol. · Pubmed #12617718 No free full text.

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