Macular Degeneration: Bressler SB

Solomon SD, Bressler SB, Hawkins BS, Marsh MJ, Bressler NM, Anonymous00106. · Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2005, USA. · Retina. · Pubmed #15805900 links to  free full text

Abstract: PURPOSE: To describe the guidelines followed by the Submacular Surgery Trials (SST) Research Group in the interpretation of color fundus photographs and fluorescein angiograms of subfoveal choroidal neovascular lesions evaluated in the SST and to assist ophthalmologists in applying the results of the SST. METHODS: Stereoscopic color fundus photographs and fluorescein angiograms of the study eye and nonstudy eye of 1,015 patients with subfoveal choroidal neovascular lesions secondary to age-related macular degeneration, ocular histoplasmosis syndrome, or idiopathic choroidal neovascularization (CNV) were obtained and graded by certified SST fundus photograph readers at the baseline examination in three randomized clinical trials comparing surgery with observation. Adherence to the inclusion and exclusion criteria and ocular features that might affect visual outcome were documented. Stereoscopic color fundus photography and fluorescein angiography were repeated 1 month after randomization for patients assigned to surgery to provide documentation that surgery was performed and to assess compliance with the surgery protocol. Photographs and fluorescein angiograms of both the study eye and the fellow eye in all patients then were obtained 3 months, 6 months, and 12 months after randomization and then annually up to 48 months. The kappa statistic was used to evaluate interobserver reliability of photograph gradings. RESULTS: Lesion components at baseline included classic CNV, occult CNV, and features contiguous to CNV, including blood, fibrous tissue, hypofluorescence not corresponding to blood, serous detachment of the retinal pigment epithelium, and prior areas of laser photocoagulation. At follow-up, fluorescein leakage from CNV was assessed peripheral to or within the area of the retinal pigment epithelium abnormality after surgery. The lesion at follow-up could include any of the features identified at baseline as well as retinal pigment epithelium abnormalities, such as mottling of the retinal pigment epithelium with a subtle transition to normal retinal pigment epithelium or a very sharply demarcated, markedly hypopigmented area that was easily distinguished from the surrounding retinal pigment epithelium. kappa statistics for interobserver reliability ranged from good (0.47) to excellent (1.00) for features graded at baseline and follow-up. CONCLUSIONS: Although some of the definitions essential to the interpretation of the SST are similar to those used in the Macular Photocoagulation Study and randomized clinical trials of photodynamic therapy with verteporfin, this guideline provides new information regarding lesion components at baseline as well as standardized descriptions of lesions after submacular surgery. These descriptions from the SST assist in understanding what lesions were studied, when additional treatment was considered after surgery, and how anatomical results should be interpreted.

Browning DJ, Altaweel MM, Bressler NM, Bressler SB, Scott IU, Anonymous00050. · Jaeb Center for Health Research, Tampa, FL 33647, USA. · Am J Ophthalmol. · Pubmed #18774122 No free full text.

Abstract: PURPOSE: To review the available information on classification of diabetic macular edema (DME) as focal or diffuse. DESIGN: Interpretive essay. METHODS: Literature review and interpretation. RESULTS: The terms focal diabetic macular edema and diffuse diabetic macular edema frequently are used without clear definitions. Published definitions often use different examination methods and often are inconsistent. Evaluating published information on the prevalence of focal and diffuse DME, the responses of focal and diffuse DME to treatments, and the importance of focal and diffuse DME in assessing prognosis is hindered because the terms are used inconsistently. A newer vocabulary may be more constructive, one that describes discrete components of the concepts such as extent and location of macular thickening, involvement of the center of the macula, quantity and pattern of lipid exudates, source of fluorescein leakage, and regional variation in macular thickening and that distinguishes these terms from the use of the term focal when describing one type of photocoagulation technique. Developing methods for assessing component variables that can be used in clinical practice and establishing reproducibility of the methods are important tasks. CONCLUSIONS: Little evidence exists that characteristics of DME described by the terms focal and diffuse help to explain variation in visual acuity or response to treatment. It is unresolved whether a concept of focal and diffuse DME will prove clinically useful despite frequent use of the terms when describing management of DME. Further studies to address the issues are needed.

Bressler NM, Bressler SB. · Retinal Vascular Center, Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2010, USA. · Invest Ophthalmol Vis Sci. · Pubmed #10711673 links to  free full text

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Scott IU, Bressler NM, Bressler SB, Browning DJ, Chan CK, Danis RP, Davis MD, Kollman C, Qin H, Anonymous00398. · Pennsylvania State University College of Medicine, Hershey, PA, USA. · Retina. · Pubmed #18185135 links to  free full text

Abstract: PURPOSE: To evaluate agreement in diabetic retinopathy severity classification by retina specialists performing ophthalmoscopy versus reading center (RC) grading of seven-field stereoscopic fundus photographs in a phase 2 clinical trial of intravitreal bevacizumab for center-involved diabetic macular edema. METHODS: Clinicians' grading scale used four levels: microaneurysms only, mild/moderate nonproliferative diabetic retinopathy (NPDR), severe NPDR, and proliferative diabetic retinopathy (PDR) or prior panretinal photocoagulation (PRP) or both. The RC scale used eight levels: microaneurysms only, mild NPDR, moderate NPDR, moderately severe NPDR, severe NPDR, mild PDR, moderate PDR, and high-risk PDR. Percent agreement and kappa statistic were defined by collapsing RC categories to match those used by clinicians. RESULTS: There was agreement in 89/118 eyes (75%) with kappa = 0.55 (95% confidence interval [0.41, 0.68]). In six eyes, disagreements were of potential substantial clinical importance: five eyes with subtle retinal neovascularization and one with a small preretinal hemorrhage identified only in photographs. CONCLUSIONS: Clinician grading of retinopathy severity had moderate agreement with RC grading and might be useful for placing eyes into broad baseline categories.

Bressler NM, Bressler SB, Haynes LA, Hao Y, Kaiser PK, Miller JW, Naor J, Potter MJ, Pournaras CJ, Reaves A, Rosenfeld PJ, Schmidt-Erfurth U, Slakter JS, Strong A, Vannier S. · No affiliation provided · Arch Ophthalmol. · Pubmed #16157822 No free full text.

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Azab M, Boyer DS, Bressler NM, Bressler SB, Cihelkova I, Hao Y, Immonen I, Lim JI, Menchini U, Naor J, Potter MJ, Reaves A, Rosenfeld PJ, Slakter JS, Soucek P, Strong HA, Wenkstern A, Su XY, Yang YC, Anonymous00313. · No affiliation provided · Arch Ophthalmol. · Pubmed #15824216 No free full text.

Abstract: OBJECTIVE: To compare the treatment effect and safety of photodynamic therapy with verteporfin using a standard (SF) or reduced (RF) light fluence rate with that of placebo therapy in patients with subfoveal minimally classic choroidal neovascularization (CNV) with age-related macular degeneration. DESIGN: Phase 2, multicenter, double-masked, placebo-controlled, randomized clinical trial. SETTING: Nineteen ophthalmology practices in North America and Europe. PARTICIPANTS: Patients with initial best-corrected visual acuity of at least 20/250 and a lesion size of no greater than 6 Macular Photocoagulation Study (MPS) disc areas. METHODS: We randomly assigned 117 patients (1:1:1) to verteporfin infusion (6 mg/m(2)) and light application with an RF rate (300 mW/cm(2)) for 83 seconds (light dose of 25 J/cm(2)) or an SF rate (600 mW/cm(2)) for 83 seconds (light dose of 50 J/cm(2)) or to placebo infusion with RF or SF. Treatment was repeated every 3 months if the treating physician noted fluorescein leakage from CNV on angiography. Patients in whom a predominantly classic lesion developed could receive open-label standard verteporfin treatment. Best-corrected visual acuity was measured every 3 months, and angiographic changes were assessed by the Photograph Reading Center through the 3-month examination unless an ocular adverse event or conversion to a predominantly classic lesion was identified by an investigator. Safety was assessed throughout the study. All outcomes were on an intent-to-treat basis. RESULTS: One hundred three (88%) of 117 patients completed the 24-month examination. Twelve (30%) of 40 patients assigned to placebo received open-label standard verteporfin treatment after confirmation of presence of predominantly classic CNV. At month 12, a loss of at least 3 lines of visual acuity occurred in 5 (14%) of 36 eyes assigned to RF and 10 (28%) of 36 eyes assigned to SF, compared with 18 (47%) of 38 eyes assigned to placebo (RF, P = .002; SF, P = .08; RF + SF, P = .004). At month 24, this loss occurred in 9 (26%) of 34 eyes assigned to RF and 17 (53%) of 32 assigned to SF, compared with 23 (62%) of 37 eyes assigned to placebo (RF, P = .003; SF, P = .45; RF + SF, P = .03). Progression to predominantly classic CNV by 24 months was more common in the placebo group (11 [28%] of 39 patients compared with 2 [5%] of 38 in the RF group [P = .007] and 1 [3%] of 37 in the SF group [P = .002]). No unexpected ocular or systemic adverse events were identified. Treatment-related, usually transient visual disturbances were 13% with SF, 10% with placebo, and 5% with RF. CONCLUSIONS: Verteporfin therapy safely reduced the risks of losing at least 15 letters (> or =3 lines) of visual acuity and progression to predominantly classic CNV for at least 2 years in individuals with subfoveal minimally classic lesions due to age-related macular degeneration measuring 6 MPS disc areas or less. Based on the overall evidence available on verteporfin therapy for these lesions, the VIM Study Group would consider recommending verteporfin therapy for relatively small minimally classic lesions similar to those enrolled in the VIM Trial.

Goldstein M, Loewenstein A, Barak A, Pollack A, Bukelman A, Katz H, Springer A, Schachat AP, Bressler NM, Bressler SB, Cooney MJ, Alster Y, Rafaeli O, Malach R, Anonymous00107. · Department of Ophthalmology, Tel-Aviv Medical Center, Israel. · Retina. · Pubmed #15805906 No free full text.

Abstract: PURPOSE: To compare the preferential hyperacuity perimeter (PHP) with an Amsler grid in detection of age-related macular degeneration (AMD). METHODS: Patients underwent refraction, visual acuity examination, PHP, Amsler grid examination, and macular photography. RESULTS: One hundred fifty patients participated in the trial. Of 19 eyes with neovascular AMD, 19 (100%) were positive on the PHP, and 10 (53%), on the Amsler grid. Of 27 eyes with geographic atrophy, 26 (96%) were positive on the PHP, and 12 (44%), on the Amsler grid. Of 20 eyes with intermediate AMD, 14 (70%) were positive on the PHP, and 4 (20%), on the Amsler grid. Of 51 eyes with early AMD, 21 (41%) were positive on the PHP, and 4 (8%), on the Amsler grid. Of 33 eyes with no AMD, 6 (18%) were positive on the PHP, and none, on the Amsler grid. Thus, 80 (68%) of 117 patients with AMD had a positive PHP, while 30 (26%) had positive results of Amsler grid examination (P < 0.001, McNemar test). CONCLUSION: The PHP had greater sensitivity, although with a relatively high rate of false-positive results for healthy individuals, than the Amsler grid in detecting AMD-related lesions.

Bressler NM, Bressler SB, Childs AL, Haller JA, Hawkins BS, Lewis H, MacCumber MW, Marsh MJ, Redford M, Sternberg P, Thomas MA, Williams GA, Anonymous00091. · SST Coordinating Center, Wilmer Clinical Trials and Biometry, 550 North Broadway, 9th Floor, Baltimore, MD 21205-2010, USA. · Ophthalmology. · Pubmed #15522364 links to  free full text

Abstract: PURPOSE: To present best-corrected visual acuity (BCVA) findings and other clinical outcomes from eyes of patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of predominantly hemorrhagic subfoveal choroidal neovascularization (CNV) associated with age-related macular degeneration. DESIGN: Randomized clinical trial (SST Group B Trial). PARTICIPANTS: Eligible patients had subfoveal choroidal neovascular lesions greater than 3.5 disk areas (8.9 mm2) composed of at least 50% blood (either blood or CNV underlying the center of the foveal avascular zone) and BCVA of 20/100 to light perception in the study eye. INTERVENTION: Patients were assigned randomly at time of enrollment to observation or surgical removal of blood and any associated CNV. MAIN OUTCOME MEASURE: A successful outcome was defined a priori as either improvement in visual acuity (VA), no change in VA, or a decline in VA of no more than 1 line (7 letters) from baseline to the 24-month examination based on an intent-to-treat analysis. RESULTS: Of 336 patients enrolled, 168 were assigned to each treatment arm; treatment arms were balanced by baseline characteristics. Of 1501 expected examinations 3 months through 36 months after baseline, 1370 (91%) were performed. Loss of > or =2 lines (> or =8 letters) of VA occurred in 56% of surgery eyes, versus 59% of observation eyes examined at 24 months. Although severe loss of VA was not the primary outcome of interest, surgery more often prevented such loss: 36% in the observation arm versus 21% in the surgery arm at the 24-month examination (chi2 P = 0.004). Of initially phakic eyes, the cumulative percentage that had undergone cataract surgery by 24 months was 44% in the surgery arm, compared with 6% in the observation arm. Twenty-seven eyes (16%) in the surgical arm, compared with 3 eyes (2%) in the observation arm, had a rhegmatogenous retinal detachment (RD). CONCLUSIONS: Submacular surgery as performed in the SST Group B Trial did not increase the chance of stable or improved VA (the primary outcome of interest) and was associated with a high risk of rhegmatogenous RD, but did reduce the risk of severe VA loss in comparison with observation. This article contains additional online-only material available at http://www.ophsource.com/periodicals/ophtha.

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.

Clemons TE, Chew EY, Bressler SB, McBee W, Anonymous00036. · AREDS Coordinating Center, The EMMES Corporation, 401 N Washington Street, Suite 700, Rockville, MD 20850-1707, USA. · Arch Ophthalmol. · Pubmed #12583787 links to  free full text

Abstract: OBJECTIVES: To describe the vision-targeted, health-related quality of life, measured with the National Eye Institute Visual Function Questionnaire (NEI-VFQ), in patients with age-related macular degeneration, cataract, or reduced visual acuity; to determine the relationship between the NEI-VFQ subscale scores and clinical measures of visual function; and to assess the internal consistency and reliability of the NEI-VFQ subscales. DESIGN: The 39-item NEI-VFQ was administered at the 5-year clinic visit to 4077 Age-Related Eye Disease Study participants. RESULTS: The subscales of the NEI-VFQ had moderate to high internal consistency (Cronbach's alpha = 0.58-0.91). The NEI-VFQ scores for participants with advanced age-related macular degeneration in 1 or both eyes, severe nuclear opacity, reduced visual acuity, or cataract surgery generally were lower than scores for disease-free participants (P<.001). CONCLUSION: These findings support the use of the NEI-VFQ as a measure of vision-targeted, health-related quality of life among patients with age-related macular degeneration, cataract, or reduced visual acuity.

Bressler NM, Arnold J, Benchaboune M, Blumenkranz MS, Fish GE, Gragoudas ES, Lewis H, Schmidt-Erfurth U, Slakter JS, Bressler SB, Manos K, Hao Y, Hayes L, Koester J, Reaves A, Strong HA, Anonymous00111. · Wilmer Photograph Reading Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2002, USA. · Arch Ophthalmol. · Pubmed #12427056 No free full text.

Abstract: OBJECTIVE: To explore how baseline lesion composition influenced vision outcomes in patients with age-related macular degeneration (AMD) undergoing photodynamic therapy with verteporfin (Visudyne) for subfoveal choroidal neovascularization (CNV) in the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy Investigation. METHODS: Patients with subfoveal lesions secondary to AMD with evidence of classic CNV were categorized into 2 subgroups based on baseline color photographs and fluorescein angiograms assessed by graders at the Wilmer Photograph Reading Center (The Johns Hopkins University School of Medicine) before any outcome analyses as follows: (1) predominantly classic CNV (area of classic CNV >/=50% of the area of the entire lesion) or (2) minimally classic CNV (area of classic CNV <50% but >0% of the area of the entire lesion). Additional exploratory analyses were performed in the predominantly classic subgroup to investigate the effects of visual acuity, lesion size, prior laser photocoagulation, phakic status, micronutrient use, and presence of occult CNV on vision outcomes. MAIN OUTCOME MEASURES: Subgroup analyses of vision and fluorescein angiographic outcomes at 1 and 2 years after study enrollment were examined in an intent-to-treat analysis from 2 multicenter, double-masked, placebo-controlled, randomized clinical trials. RESULTS: Compared with patients who had minimally classic CNV, patients with predominantly classic CNV had a worse initial mean visual acuity and smaller lesions and were more likely to have lesions that included blood or blocked fluorescence. When evaluated by treatment assignment and lesion composition, 84% to 88% completed the month 24 examination. In the subgroup with predominantly classic lesions, visual acuity outcomes were consistently better in verteporfin-treated patients. Outcomes for patients with predominantly classic lesions without occult CNV tended to be better than outcomes for patients with predominantly classic lesions with occult CNV, although the former tended to have smaller lesions and lower levels of visual acuity at baseline. Contrast sensitivity and fluorescein angiographic outcomes (total lesion size, progression of classic CNV, and absence of classic CNV) were better in verteporfin-treated patients than in placebo-treated patients in the predominantly classic and the minimally classic CNV subgroups. In patients with predominantly classic CNV, no interaction of the treatment benefit by phakic status, micronutrient use, or prior laser photocoagulation therapy was noted. CONCLUSIONS: Verteporfin therapy can safely reduce the risk of moderate and severe vision loss in patients with subfoveal lesions that are predominantly classic CNV secondary to AMD. While this benefit seemed to be even greater in the absence of occult CNV, the effect may be related to the smaller lesions and worse visual acuity associated with predominantly classic lesions without occult CNV and not solely to the lesion composition itself. These analyses support initial reports that verteporfin therapy should be used to treat patients with AMD who have predominantly classic CNV, with or without occult CNV, but suggest that further investigations should be performed to determine if lesions with a minimally classic composition might benefit when they are smaller and have lower levels of visual acuity.

Blumenkranz MS, Bressler NM, Bressler SB, Donati G, Fish GE, Haynes LA, Lewis H, Miller JW, Monés JM, Potter MJ, Pournaras C, Reaves A, Rosenfeld PJ, Schachat AP, Schmidt-Erfurth U, Sickenburg M, Singerman LJ, Slakter JS, Strong A, Vannier S, Anonymous00194. · No affiliation provided · Arch Ophthalmol. · Pubmed #12365909 No free full text.

Abstract: OBJECTIVE: To report vision and safety outcomes from an extension of a 2-year investigation evaluating verteporfin photodynamic therapy in patients with age-related macular degeneration with subfoveal choroidal neovascularization (CNV). DESIGN AND SETTING: Open-label extension of selected patients from 2 multicenter, double-masked, placebo-controlled, randomized clinical trials, the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) Investigation, at 22 ophthalmology practices in Europe and North America. PARTICIPANTS: Patients enrolled in the TAP Investigation and followed up for at least 24 months in whom verteporfin therapy to CNV might reduce the risk of further vision loss. METHODS: Before receiving verteporfin therapy in the extension, eligible patients signed a written informed consent form accompanied by an oral consent process approved by local institutional review boards. Methods were similar to those described for 1- and 2-year results, with follow-up examinations beyond 2 years continuing at 3-month intervals with a few exceptions, including that extension patients with fluorescein leakage from CNV were to receive open-label verteporfin therapy irrespective of their original treatment assignment. RESULTS: Of 402 patients in the verteporfin group, 351 (87.3%) completed the month 24 examination; 320 (91.2%) of these enrolled in the extension study. The enrolled participants included 124 (78.0%) of the 159 verteporfin-treated patients with lesions composed of predominantly classic CNV at baseline, of whom 105 (84.7%) completed the month 36 examination. Verteporfin-treated patients with this lesion composition at baseline who participated in the extension study, with or without a month 36 examination, appeared more likely to have a younger age, better level of visual acuity, absence of fluorescein leakage from classic CNV, or no progression of classic CNV beyond the baseline boundaries of the lesion at the month 24 examination compared with those who did not enroll in the extension. For the 105 patients with a predominantly classic baseline lesion composition who completed the month 36 examination, an average of 1.3 treatments were given from the month 24 examination up to, but not including, the month 36 examination. A letter score loss in the study eye of at least 15 from baseline for these patients occurred in 39 (37.5%) at the month 24 examination compared with 44 (41.9%) of these patients at the month 36 examination. Visual acuity changed little from the month 24 examination (mean, -1.9 lines) to the month 36 examination (mean, -2.0 lines) for these eyes. Verteporfin-treated patients had little change in the mean visual acuity lost and few or no additional instances of infusion-related back pain or photosensitivity reactions from month 24 to month 36. Two patients originally assigned to placebo had acute severe vision decrease within 7 days after verteporfin treatment during the extension. One patient originally assigned to verteporfin had acute severe vision decrease after verteporfin treatment of the fellow eye during the extension. CONCLUSIONS: Vision outcomes for verteporfin-treated patients with predominantly classic lesions at baseline remained relatively stable from month 24 to month 36, although only approximately one third of the verteporfin-treated patients originally enrolled with this lesion composition had a month 36 examination. From these results, the TAP Study Group identified no safety concerns to preclude repeating photodynamic therapy with verteporfin. Additional treatment was judged likely to reduce the risk of further vision loss. Caution appears warranted in the absence of comparison with an untreated group during the extension and since not all patients in the TAP Investigation participated in the TAP Extension.

Bressler NM, Bressler SB, Hawkins BS, Marsh MJ, Sternberg P, Thomas MA, Anonymous00036. · No affiliation provided · Am J Ophthalmol. · Pubmed #11024412 No free full text.

Abstract: PURPOSE: To report complications and changes in vision during 2 years of follow-up of patients with age-related macular degeneration assigned randomly to surgical removal or to laser photocoagulation of subfoveal recurrent neovascular lesions in a pilot trial designed to test methods, to refine estimates of outcome rates, and to project patient accrual rates for a larger multicenter randomized trial to evaluate submacular surgery. PATIENTS AND METHODS: Eligible patients with previous laser photocoagulation of extrafoveal or juxtafoveal choroidal neovascularization secondary to age-related macular degeneration were enrolled at 15 collaborating clinical centers. Assignments to treatment arm were made by personnel at a central coordinating center. Adherence to eligibility criteria and treatment assignment was assessed centrally at a photograph reading center. Patients were examined at 3, 6, 12, and 24 months after treatment for data collection purposes. Outcome measures reported include treatment complications, adverse events, requirements for additional treatment, and 2-year changes in visual acuity from baseline. RESULTS: Of 70 patients enrolled, 36 were assigned to laser photocoagulation and 34 to submacular surgery; all were treated as assigned. One patient in each group died before the 2-year examination. Visual acuity was measured at the 2-year examination for 31 of the surviving patients (89%) in the laser arm and for 28 of the surviving patients (85%) in the surgery arm. The 2-year measurements for 36 of the 59 patients (61%) were made by an examiner masked to treatment assignment and to the identity of the study eye. Improvements and losses of visual acuity were observed in both treatment arms; 20 of 31 study eyes (65%) in the laser arm and 14 of 28 study eyes (50%) in the surgery arm had visual acuity 2 years after enrollment that was better than or no more than 1 line worse than the baseline level. Changes in visual acuity and the size of the central macular lesions from baseline to the 2-year examination were similar in the treatment arms. Few serious complications were observed in either arm at the time of initial treatment; serious adverse events were rare. During follow-up, 11 laser-treated eyes and 18 surgically treated eyes had additional intraocular procedures. CONCLUSIONS: The data from this pilot trial suggest no reason to prefer submacular surgery over laser photocoagulation for treatment of patients with age-related macular degeneration who have lesions similar to those studied in this pilot trial. Any clinical trial designed to compare submacular surgery with laser photocoagulation in eyes with age-related macular degeneration and subfoveal recurrent neovascular lesions must enroll several hundred patients in order to reach a statistically valid conclusion regarding differences between these two methods of treatment with respect to either changes in visual acuity or complication rates.

Muñoz B, West SK, Rubin GS, Schein OD, Quigley HA, Bressler SB, Bandeen-Roche K. · Wilmer Eye Institute, The Johns Hopkins University, 600 N Wolfe St, Room 116, Baltimore, MD 21287, USA. · Arch Ophthalmol. · Pubmed #10865321 No free full text.

Abstract: OBJECTIVE: To determine the causes of blindness and visual impairment in a population-based sample of older Americans. METHODS: A random sample of 3821 residents of Salisbury, Md, between the ages of 65 and 84 years was identified from Medicare records. Sixty-six percent (2520 persons) agreed to undergo an eye examination; 26% of the participants were African American. The clinical examination included acuity testing with an Early Treatment Diabetic Retinopathy Study chart and standardized refraction testing for those with a visual acuity worse than 20/30, slitlamp and dilated retinal examination by an ophthalmologist, tonometry, lens and fundus photography, and a suprathreshold visual field test. Visual impairment was defined as a best-corrected acuity in the better-seeing eye worse than 20/40 and better than 20/200, while blindness was acuity in the better-seeing eye of 20/200 or worse. For those with a visual acuity worse than 20/40 in either eye, one or more causes were assigned by an ophthalmologist and a final cause for each eye was confirmed by a panel of 3 subspecialty ophthalmologists (O.D.S., H.A.Q., and S.B.B.) based on all available evidence. RESULTS: Bilateral presenting acuity worse than 20/40 increased from 4% in the 65- to 74-year age group to 16% in the 80- to 84-year age group. One third of those with presenting acuity worse than 20/40 improved to 20/40 or better with refraction. Overall, 4.5% had a best-corrected acuity worse than 20/40. African Americans were more likely to remain visually impaired than were whites despite refraction (odds ratio [95% confidence interval], 1.7 [1.1-2.6]). Whites were most often impaired or blind from age-related macular degeneration (1.2% vs 0.5%; P=.09). African Americans had higher rates of impairment and blindness from cataract or posterior capsular opacification (2.7% vs 1.1%; P=.006), glaucoma (0.9% vs 0.1%; P=.006), and diabetic retinopathy (1.2% vs 0.2%; P=. 004). CONCLUSIONS: More than half of those with visual impairment or blindness had conditions that were either surgically treatable or potentially preventable. African Americans had a disproportionate number of blinding diseases, particularly those amenable to eye care intervention. Targeted interventions for specific populations to increase appropriate eye care use would greatly improve vision and function in older Americans. Arch Ophthalmol. 2000;118:819-825

Weisz JM, Bressler NM, Bressler SB, Schachat AP. · Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine and Hospital, Baltimore, Maryland, USA. · Ophthalmology. · Pubmed #10485530 No free full text.

Abstract: OBJECTIVE: To evaluate whether ketorolac ophthalmic drops prescribed four times a day can be associated with improved visual acuity and prompt resolution of edema for patients with pseudophakic cystoid macular edema identified more than 24 months after cataract surgery. DESIGN: Prospective, nonrandomized, comparative (subject self-controlled) trial. PARTICIPANTS: The records of nine patients who had pseudophakic cystoid macular edema more than 24 months after cataract surgery at the time treatment commenced were identified at the Wilmer Retinal Vascular Center from September 1, 1996, through March 1, 1997. MAIN OUTCOME MEASURES: Best-corrected visual acuities measured on a retroilluminated Bailey-Lovie chart approximately every 3 months, contact lens biomicroscopy, and fluorescein angiography following ketorolac. INTERVENTION: Commercially available ketorolac ophthalmic drops 0.5% were prescribed for the affected eye four times a day for at least 3 months and continued until edema resolved. RESULTS: Ten eyes of nine patients were identified more than 24 months after cataract extraction (median, 59 months). Seven eyes (70%) improved (mean, +3.2 lines; range, +1 to +13 lines), including six by 2 or more lines 3 months after treatment initiation. Two eyes (20%) were unchanged, and one eye (10%) was 1 line worse. All seven eyes that improved 1 line or more had some or complete angiographic resolution of fluorescein dye leakage. In these seven eyes, ketorolac was discontinued when dye leakage completely resolved or failed to continue to improve on periodic 3-month follow-up examinations. In all seven eyes, recurrence of edema was noted within 3 months after ketorolac was stopped. CONCLUSIONS: Chronic pseudophakic cystoid macular edema identified more than 24 months after cataract surgery can improve with topical ketorolac but probably requires persistent use.

Scott IU, Danis RP, Bressler SB, Bressler NM, Browning DJ, Qin H, Anonymous00054. · Department of Ophthalmology and Public Health Sciences, Penn State Hershey Eye Center, Penn State College of Medicine, Hershey, Pennsylvania, USA. · Retina. · Pubmed #19373126 No free full text.

Abstract: PURPOSE: To report visual acuity and anatomic changes from baseline to 12 months after modified Early Treatment Diabetic Retinopathy Study (ETDRS)-style (focal/grid) photocoagulation in eyes with non-center-involved (non-CI) clinically significant macular edema. METHODS: Visual acuity, optical coherence tomography, fluorescein angiography, and fundus photography data were analyzed from eyes with non-CI clinically significant macular edema treated with modified ETDRS-style (focal/grid) photocoagulation in a Diabetic Retinopathy Clinical Research Network trial. RESULTS: Among the 22 eyes (of 22 patients) with 12-month follow-up, median visual acuity letter score remained within 1 letter of baseline over 12 months. The median central subfield retinal thickness decreased by 10 mum, median total macular volume decreased by 0.2 mm, and median fluorescein leakage area within the grid decreased by 0.7 disk areas. CONCLUSION: We are unaware of any other systematic evaluation of eyes with non-CI clinically significant macular edema since the ETDRS. Focal/grid laser in these non-CI eyes was associated with relatively stable visual acuity and retinal thickness measurements, and decreased fluorescein leakage area at 1 year. One-year visual acuity results are consistent with those published by the ETDRS, despite the intervening significant differences in the management of diabetes. Although this was a small study without a concurrent control group, the ETDRS recommendation to consider focal/grid laser in eyes with non-CI clinically significant macular edema still seems appropriate.

Browning DJ, Apte RS, Bressler SB, Chalam KV, Danis RP, Davis MD, Kollman C, Qin H, Sadda S, Scott IU, Anonymous00031. · Charlotte Eye Ear Nose and Throat Assoc, PA, Charlotte, North Carolina, USA. · Retina. · Pubmed #19174719 No free full text.

Abstract: PURPOSE: To determine whether the extensiveness of diabetic macular edema using a 10-step scale based on optical coherence tomography explains pretreatment variation in visual acuity and predicts change in macular thickness or visual acuity after laser photocoagulation. METHODS: Three hundred twenty-three eyes from a randomized clinical trial of two methods of laser photocoagulation for diabetic macular edema were studied. Baseline number of thickened optical coherence tomography subfields was used to characterize diabetic macular edema on a 10-step scale from 0 to 9. Associations were explored between baseline number of thickened subfields and baseline fundus photographic variables, visual acuity, central subfield mean thickness (CSMT), and total macular volume. Associations were also examined between baseline number of thickened subfields and changes in visual acuity, CSMT, and total macular volume at 3.5 and 12 months after laser photocoagulation. RESULTS: For baseline visual acuity, the number of thickened subfields explained no more variation than did CSMT, age and fluorescein leakage. A greater number of thickened subfields was associated with a greater baseline CSMT, total macular volume, area of retinal thickening, and degree of thickening at the center of the macula (r = 0.64, 0.77, 0.61-0.63, and 0.45, respectively) and with a lower baseline visual acuity (r = 0.38). Baseline number of thickened subfields showed no association with change in visual acuity (r < or = 0.01-0.08) and weak associations with change in CSMT and total macular volume (r from 0.11 to 0.35). CONCLUSION: This optical coherence tomography based assessment of the extensiveness of diabetic macular edema did not explain additional variation in baseline visual acuity above that explained by other known important variables nor predict changes in macular thickness or visual acuity after laser photocoagulation.

Chew EY, Sperduto RD, Milton RC, Clemons TE, Gensler GR, Bressler SB, Klein R, Klein BE, Ferris FL. · National Eye Institute, Bethesda, Maryland, USA. · Ophthalmology. · Pubmed #19091420 No free full text.

Abstract: PURPOSE: To assess the risk of advanced age-related macular degeneration (AMD) developing after cataract surgery. DESIGN: Cohort study. PARTICIPANTS: Four thousand five hundred seventy-seven participants (8050 eyes) from a multicenter, controlled, randomized clinical trial, the Age-Related Eye Disease Study (AREDS). METHODS: Development of advanced AMD, either neovascular (NV) AMD or geographic atrophy (GA), was evaluated with annual fundus photographs, and history of cataract surgery was assessed every 6 months. Cox proportional hazard models with time-dependent covariates were conducted for NV AMD and GA separately. MAIN OUTCOME MEASURES: Neovascular AMD, GA, and central GA (CGA; involving the center of the macula). RESULTS: The Cox proportional hazards model of right eyes showed nonsignificant hazard ratios of 1.20 (95% confidence interval [CI], 0.82-1.75) for NV AMD, 0.80 (95% CI, 0.61-1.06) for GA, and 0.87 (95% CI, 0.64-1.18) for CGA. Similar results were obtained for left eyes: 1.07 (95% CI, 0.72-1.58) for NV AMD, 0.94 (95% CI, 0.71-1.25) for GA, and 0.86 (95% CI, 0.63-1.19) for CGA. For participants with advanced AMD in 1 eye (AREDS category 4), the hazard ratios for fellow eyes were 1.08 (95% CI, 0.65-1.72) for NV AMD and 0.98 (95% CI, 0.64-1.49) for CGA. CONCLUSIONS: The AREDS results showed no clear effect of cataract surgery on the risk of progression to advanced AMD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Ip MS, Bressler SB, Antoszyk AN, Flaxel CJ, Kim JE, Friedman SM, Qin H, Anonymous00381. · University of Wisconsin Fundus Photograph Reading Center, Madison, WI, USA. · Retina. · Pubmed #18698292 No free full text.

Abstract: PURPOSE: To compare baseline demographic, systemic, and ocular characteristics within age and racial subgroups among participants in this Diabetic Retinopathy Clinical Research Network clinical trial and to compare this cohort with other cohorts enrolled in phase 3 clinical trials for diabetic retinopathy. METHODS: Thirty-six month, randomized, controlled, multicenter clinical trial of 693 participants with diabetic macular edema enrolled at 88 clinical sites in the United States. Participants were categorized into self-reported race/ethnicity subgroups and into one of three age groups: 18 to <60, 60 to <70, and 70 and older. RESULTS: Mean age of participants was 63 years, 72% were white, and median visual acuity letter score was 62 (approximately 20/63). No substantial difference was identified between racial subgroups for any baseline variable. Older participants were more likely to have Type 2 diabetes mellitus and longer duration disease. The most frequent levels of diabetic retinopathy among 840 study eyes were moderate (level 43) to moderately severe (level 47) nonproliferative disease. CONCLUSION: While the racial composition of this cohort does not differ from other cohorts in large phase 3 trials that have evaluated participants with diabetic retinopathy, the inclusion of many subjects over age 70 and a better level of glycemic control are distinguishing features.

Browning DJ, Glassman AR, Aiello LP, Bressler NM, Bressler SB, Danis RP, Davis MD, Ferris FL, Huang SS, Kaiser PK, Kollman C, Sadda S, Scott IU, Qin H, Anonymous00193. · Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647, USA. · Ophthalmology. · Pubmed #18675696 No free full text.

Abstract: OBJECTIVE: To evaluate optical coherence tomography (OCT) measurements and methods of analysis of OCT data in studies of diabetic macular edema (DME). DESIGN: Associations of pairs of OCT variables and results of 3 analysis methods using data from 2 studies of DME. PARTICIPANTS: Two hundred sixty-three subjects from a study of modified Early Treatment of Diabetic Retinopathy Study (mETDRS) versus modified macular grid (MMG) photocoagulation for DME and 96 subjects from a study of diurnal variation of DME. METHODS: Correlations were calculated for pairs of OCT variables at baseline and for changes in the variables over time. Distribution of OCT measurement changes, predictive factors for OCT measurement changes, and treatment group outcomes were compared when 3 measures of change in macular thickness were analyzed: absolute change in retinal thickness, relative change in retinal thickness, and relative change in retinal thickening. MAIN OUTCOME MEASURES: Concordance of results using different OCT variables and analysis methods. RESULTS: Center point thickness correlated highly with central subfield mean thickness (CSMT) at baseline (0.98-0.99). The distributions of changes in CSMT were approximately normally distributed for absolute change in retinal thickness and relative change in retinal thickness, but not for relative change in retinal thickening. Macular thinning in the mETDRS group was significantly greater than in the MMG group when absolute change in retinal thickness was used, but not when relative change in thickness and relative change in thickening were used. Relative change in macular thickening provides unstable data in eyes with mild degrees of baseline thickening, unlike the situation with absolute or relative change in retinal thickness. CONCLUSIONS: Central subfield mean thickness is the preferred OCT measurement for the central macula because of its higher reproducibility and correlation with other measurements of the central macula. Total macular volume may be preferred when the central macula is less important. Absolute change in retinal thickness is the preferred analysis method in studies involving eyes with mild macular thickening. Relative change in thickening may be preferable when retinal thickening is more severe.

Davis MD, Bressler SB, Aiello LP, Bressler NM, Browning DJ, Flaxel CJ, Fong DS, Foster WJ, Glassman AR, Hartnett ME, Kollman C, Li HK, Qin H, Scott IU, Anonymous00289. · Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA. · Invest Ophthalmol Vis Sci. · Pubmed #18316700 links to  free full text

Abstract: PURPOSE: To explore the correlation between optical coherence tomography (OCT) and stereoscopic fundus photographs (FP) for the assessment of retinal thickening (RT) in diabetic macular edema (DME) within a clinical trial. METHODS: OCT, FP, and best corrected visual acuity (VA) measurements were obtained in both eyes of 263 participants in a trial comparing two photocoagulation techniques for DME. Correlation coefficients (r) were calculated comparing RT measured by OCT, RT estimated from FP, and VA. Principal variables were central subfield retinal thickness (CSRT) obtained from the OCT fast macular map and DME severity assessed by a reading center using a seven-step photographic scale combining the area of thickened retina within 1 disc diameter of the foveal center and thickening at the center. RESULTS: Medians (quartiles) for retinal thickness within the center subfield by OCT at baseline increased from 236 (214, 264) microm in the lowest level of the photographic scale to 517 (455, 598) microm in the highest level (r = 0.67). However, CSRT interquartile ranges were broad and overlapping between FP scale levels, and there were many outliers. Correlations between either modality and VA were weaker (r = 0.57 for CSRT, and r = 0.47 for the FP scale). OCT appeared to be more reproducible and more sensitive to change in RT between baseline and 1 year than was FP. CONCLUSIONS: There was a moderate correlation between OCT and FP assessments of RT in patients with DME and slightly less correlation of either measure with VA. OCT and FP provide complementary information but neither is a reliable surrogate for VA.

Bressler SB, Muñoz B, Solomon SD, West SK, Anonymous00118. · The Wilmer Eye Institute, Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287-9228, USA. · Arch Ophthalmol. · Pubmed #18268216 links to  free full text

Abstract: OBJECTIVE: To determine differences in the prevalence of age-related macular degeneration (AMD) and its fundus manifestations in a population-based sample of older black and white Americans. DESIGN: Cross-sectional population-based study of 2520 participants of whom 1854 are white and 666 are black. Mean age was 73.5 years. Stereoscopic color fundus photographs were graded for presence, severity, and location of drusen, retinal pigment epithelium abnormalities, and choroidal neovascularization or disciform scarring. RESULTS: Drusen at least 64 microm in size were identified in 56% of black and white individuals within 3000 microm of the foveal center, but drusen larger than 125 microm were more common among white participants (16% white vs 11% black individuals). Drusen at least 250 microm in size, confluent drusen, or a larger area (> 10%) occupied by drusen were each more common among white participants. White individuals were 3 times more likely to have focal hyperpigmentation than black individuals. Racial differences were most pronounced for features within the central 1500-microm macular zone. Neovascular AMD was present in 1.7% of white participants and 1.1% of black participants (age-adjusted, P = .38), whereas geographic atrophy was more common in white than black individuals (1.8% vs 0.3%; age-adjusted, P = .02). CONCLUSIONS: White persons are generally more likely than black persons to have medium or large drusen, focal pigment abnormalities, and advanced AMD. Racial differences were prominent for nonneovascular AMD features only when present in the central zone. These data suggest that black individuals may have a mechanism for protection in the central zone against these critical fundus features, which themselves convey high risk of progression to advanced AMD.

Chang MA, Bressler SB, Munoz B, West SK. · Retina Division and Dana Center for Preventative Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. · Invest Ophthalmol Vis Sci. · Pubmed #18263809 links to  free full text

Abstract: PURPOSE: To evaluate risk factors for the incidence and progression of age-related macular degeneration (AMD) in a racially heterogeneous, geriatric population. METHODS: Subjects (n = 2240) aged 65 to 84 years underwent 2 examinations separated by 2 years, of which 1937 subjects (85%) were included in this report. Fundus photographs were performed at each examination and were graded by trained readers. Multivariate logistic regression models adjusted for age, sex, race, and clustering between eyes were used to evaluate risk factors for AMD incidence and progression. RESULTS: Smoking was a strong, dose-dependent, risk factor for progression from medium size drusen to large drusen or pigmentary abnormalities within the central 1500-microm macular zone. Smoking was also a strong risk factor for development of incident focal pigmentation within 3000 microm of the foveal center. White participants were significantly more likely than blacks to develop large drusen and focal pigmentation and to progress from medium- to large-sized drusen or pigment abnormalities within the central 1500 microm macular zone. However, whites did not have an increased risk of progression from large drusen or pigment abnormalities within the central 1500-microm perimacular zone to foveal GA or CNV when compared with blacks. CONCLUSIONS: Smoking and race are important risk factors for progression from medium to large drusen or to pigment abnormalities within the central 1500-microm macular zone. Limitations in the power of this study preclude assessment of the roles of smoking and race on the ultimate progression to foveal GA or CNV once central large drusen or pigment abnormalities are present.

Charkoudian LD, Gower EW, Solomon SD, Schachat AP, Bressler NM, Bressler SB. · Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. · Ophthalmology. · Pubmed #18096234 No free full text.

Abstract: OBJECTIVE: To describe micronutrient usage patterns among patients at a tertiary ophthalmic center. DESIGN: Cross-sectional clinical case series. PARTICIPANTS: Three hundred thirty-two adult patients with a diagnosis of age-related macular degeneration (AMD). METHODS: Participants were surveyed about micronutrient usage patterns. The treating ophthalmologist recorded AMD severity using the Age-Related Eye Disease Study (AREDS) classification system. MAIN OUTCOME MEASURES: Responses to study questionnaire and level of AMD severity. RESULTS: Among 332 participants, 309 (93%) were using supplements, among which 174 (52%) supplemented with an AREDS-like formulation. Of these 174, 140 (80%) were considered AREDS supplement candidates based on study guidelines. Applying AREDS supplementation guidelines to the full cohort, 228 (69%) were candidates for supplementation. Only 140 (61%) of these individuals were confirmed to be using the correct formulation and dosage; an additional 13 (6%) used the AREDS formulation but were not using the recommended dosage. CONCLUSIONS: Among patients receiving care for AMD at a tertiary retinal center, more than one third of those deemed candidates for AREDS-type supplements were not using them or were using an incorrect dose. Furthermore, nearly one fifth of participants who were using high-dose supplements did not have a level of AMD anticipated to benefit from usage. Increased patient education is needed regarding the recommendations of AREDS.

Klein ML, Ferris FL, Armstrong J, Hwang TS, Chew EY, Bressler SB, Chandra SR, Anonymous00008. · Devers Eye Institute, Legacy Good Samaritan Hospital and Medical Center, Portland, Oregon, USA. · Ophthalmology. · Pubmed #17981333 No free full text.

Abstract: PURPOSE: To determine specific retinal precursor lesions and sequence of events preceding the onset of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD). DESIGN: Retrospective review. PARTICIPANTS: All participants in the Age-Related Eye Disease Study (AREDS) at 2 clinical centers (Devers Eye Institute, Portland, Oregon, and University of Wisconsin, Madison, Wisconsin) in whom GA initially appeared in at least one eye a minimum of 4 years after the baseline study visit. METHODS: All stereoscopic fundus photographs taken before the appearance of GA in the involved (study) eye were reviewed. Fundus features at the site of future GA were graded and recorded. Three graders reviewed photographs, with independent grading and adjudication by mutual agreement. Features graded included drusen (classified by size and confluence), focal hyperpigmentation, hypopigmentation, and refractile deposits. The time between first appearance of these features and initial appearance of GA was recorded. MAIN OUTCOME MEASURE: Appearance of GA. RESULTS: Of all AREDS participants at the 2 sites, 95 eyes of 77 developed GA at least 4 years after entrance into the study. Average time from baseline to initial appearance of GA was 6.6 years (range, 4-11). Drusen were found in 100% of eyes at the site of later developing GA, drusen >125 mum in diameter in 96% of eyes, confluent drusen in 94%, hyperpigmentation in 96%, drusen > 250 mum in 83%, hypopigmentation in 82%, and refractile deposits in 23%. Time from lesion appearance to onset of GA varied by lesion type, ranging from 5.9 years for drusen confluence to 2.5 years for hypopigmentation or refractile deposits. Lesions generally followed a uniform sequence of appearance. CONCLUSIONS: By focusing on the location of initial GA appearance and then retrospectively analyzing prior photographs, we were able to identify specific precursor lesions and the most common sequence of events leading to GA formation in eyes with AMD. The progression was usually characterized by large drusen formation and development of hyperpigmentation, followed by regression of drusen, appearance of hypopigmentation, and ultimately development of GA, sometimes preceded by the appearance of refractile deposits.