Macular Degeneration: Marsh MJ

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.

Childs AL, Bressler NM, Bass EB, Hawkins BS, Mangione CM, Marsh MJ, Miskala PH, Anonymous00092. · SST Coordinating Center, 550 North Broadway, 9th Floor, Baltimore, MD 21205, USA. · Ophthalmology. · Pubmed #15522365 links to  free full text

Abstract: PURPOSE: To present and compare findings from health-related quality-of-life (HRQOL) interviews conducted with patients enrolled in the SST Group B Trial evaluating surgical removal of subfoveal choroidal neovascular lesions associated with age-related macular degeneration versus observation. DESIGN: Randomized clinical trial. PARTICIPANTS: Eligible patients had predominantly hemorrhagic subfoveal choroidal neovascular lesions (total lesion size of >3.5 disc areas, area of blood at least 50% of the lesion area, and at least 75% of blood posterior to the equator) and best-corrected visual acuity (VA) of 20/100 to <20/1600 but at least light perception in the study eye. Three hundred thirty-six patients enrolled after baseline quality-of-life interviews, 168 assigned to each of surgery or observation. METHODS: Clinical and HRQOL data were collected before randomization and at 6, 12, 24, 36, and 48 months after enrollment. Baseline clinical evidence was used to stratify patients as having unilateral or bilateral neovascularization at the time of randomization. The HRQOL interviews included the National Eye Institute Visual Function Questionnaire (NEI-VFQ), the 36-item Short Form Health Survey, and the Hospital Anxiety and Depression Scale. MAIN OUTCOMES MEASURE: Two-year change in NEI-VFQ. RESULTS: At 24 months after enrollment, overall NEI-VFQ scores had a median decrease of 1 point from baseline in the observation arm (95% confidence interval [CI]: -4 to 3 points) and no change in the surgery arm (95% CI: -3 to 3 points) (P = 0.70). Changes from baseline on NEI-VFQ subscales also were similar between treatment arms. Differences in scores by unilateral or bilateral involvement seen at baseline in each treatment arm persisted throughout follow-up for most outcomes. Planned analyses stratified by VA showed trends (P = 0.17) in favor of surgery at 24 months in the patients with baseline VA greater than 20/200 for the NEI-VFQ scale (3.5-point median increase from baseline in the surgery arm [95% CI: -4 to 7] vs. a 1-point median loss from baseline in the observation arm [95% CI: -6 to 4]). CONCLUSIONS: No difference was detected with respect to vision-targeted quality-of-life outcomes for patients randomized to surgery or observation in the SST Group B Trial. This article contains additional online-only material available at www.ophsource.com/periodicals/ophtha.

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.

Miskala PH, Bass EB, Bressler NM, Childs AL, Hawkins BS, Mangione CM, Marsh MJ, Anonymous00090. · SST Coordinating Center, 550 North Broadway, 9th Floor, Baltimore, MD 21205-2010, USA. · Ophthalmology. · Pubmed #15522363 links to  free full text

Abstract: PURPOSE: To describe health-related quality of life (HRQOL), overall and in patients with unilateral or bilateral choroidal neovascularization (CNV), in a clinical trial (Group N Trial) comparing observation and surgical removal of subfoveal CNV secondary to age-related macular degeneration (AMD). DESIGN: Randomized clinical trial. PARTICIPANTS: Eligible patients had untreated subfoveal CNV and AMD, best-corrected visual acuity (VA) of 20/100 to 20/800, classic CNV on fluorescein angiography, and a total subfoveal lesion size of < or =9.0 disc areas in the study eye. METHODS: Health-related quality of life data (the National Eye Institute Visual Function Questionnaire [NEI-VFQ], 36-item Short Form Health Survey [SF-36], and Hospital Anxiety and Depression Scale [HADS]) and clinical data were collected at baseline and at 6, 12, 24, 36, and 48 months. Patients were divided into unilateral and bilateral CNV subgroups based on fluorescein angiographic and clinical evidence. MAIN OUTCOME MEASURE: Two-year change in the NEI-VFQ. RESULTS: Of 454 patients enrolled, 228 were assigned to observation and 226 to surgery. At baseline, median overall NEI-VFQ scores were 67 in the observation group and 69 in the surgery group; by 2 years, the observation group had lost a median of 3 points (95% confidence interval [CI]: -6 to -2), and the surgery group gained a median of 1 point (CI: -1 to 3). The largest difference was observed for the mental health subscale, where the observation group lost a median of 5 points (CI: -5 to 0), and the surgery group gained a median of 5 points (CI: 0-10) by 2 years. Treatment differences in median 2-year changes in NEI-VFQ scores favored surgery by up to 10 points for unilateral cases and up to 8 points for bilateral cases. No treatment difference in 2-year change was observed for the SF-36 physical component summary; 2-year change in the mental component summary favored surgery by 2 points. Few patients (2%-4%) had HADS definite anxiety or depression at baseline or at 24 months. CONCLUSIONS: Although HRQOL outcomes were better in the submacular surgery arm than in the observation arm, surgery (per protocol) is not recommended because VA outcomes (reported elsewhere) were similar in the treatment arms. 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.

Dong LM, Childs AL, Mangione CM, Bass EB, Bressler NM, Hawkins BS, Marsh MJ, Miskala P, Jaffee HA, McCaffrey LA, Anonymous00315. · Wilmer Clinical Trials and Biometry, The Wilmer Ophthalmologic Institute, 550 N. Broadway, 9th Floor, Baltimore, MD 21205-2010, USA. · Am J Ophthalmol. · Pubmed #15234287 No free full text.

Abstract: PURPOSE: To describe the effect of subfoveal choroidal neovascularization (CNV) from age-related macular degeneration (AMD) on health-related quality of life (HRQOL) of patients at enrollment in two randomized clinical trials; to examine the relation of visual acuity to HRQOL; to compare HRQOL scores between participants with unilateral and bilateral CNV independent of other characteristics. DESIGN: Randomized clinical trials. METHODS: Two Submacular Surgery Trials (SST) recruited patients with AMD and either new subfoveal CNV (Group N Trial) or predominantly hemorrhagic CNV (Group B Trial). Health-related quality of life interviews included the National Eye Institute Visual Function Questionnaire [NEI-VFQ], the SF-36 Health Survey, and the Hospital Anxiety and Depression Scale [HADS]. Linear correlation and regression analyses were used to relate baseline HRQOL scores to visual acuity and bilateral disease. RESULTS: Interview data were analyzed for 789 AMD patients: 454 patients in the Group N Trial and 335 patients in the Group B Trial. Participants reported poor vision-related functioning in many domains measured by the NEI-VFQ (mean overall scores of 65 for Group N and 63 for Group B). Visual acuity of the better eye was strongly associated with NEI-VFQ scores but not with SF-36 or HADS scores. After adjusting for visual acuity of the better eye and other factors, bilateral cases had NEI-VFQ overall scores six points lower than unilateral cases in Group N Trial and 10 points lower than unilateral cases in the Group B Trial. CONCLUSIONS: Subfoveal CNV profoundly affects vision-related quality of life. The effect is more pronounced with bilateral disease, even after controlling for visual acuity.

Miskala PH, Hawkins BS, Mangione CM, Bass EB, Bressler NM, Dong LM, Marsh MJ, McCaffrey LD, Anonymous00023. · Submacular Surgery Trials Coordinating Center, Wilmer Clinical Trials and Biometry, Baltimore, MD 21205, USA. · Arch Ophthalmol. · Pubmed #12695250 links to  free full text

Abstract: BACKGROUND: The National Eye Institute Visual Function Questionnaire (NEI-VFQ) measures vision-targeted quality of life, but it is unclear whether it is sensitive to changes within individuals over time. OBJECTIVE: To determine the responsiveness of the NEI-VFQ to "within-individual" changes in visual acuity in patients who had subfoveal choroidal neovascularization in at least one eye secondary to age-related macular degeneration, ocular histoplasmosis syndrome, or idiopathic causes, and who participated in randomized trials of submacular surgery. METHODS: Trained telephone interviewers administered the NEI-VFQ as part of annual follow-up data collection for pilot trials and larger clinical trials of submacular surgery. Best-corrected visual acuity was measured by local vision examiners at 12 months after enrollment and, typically, by central "traveling" vision examiners at 24 months after enrollment. Changes in visual acuity and NEI-VFQ scores from 12 to 24 months were analyzed using linear regression methods. RESULTS: Two-hundred eighteen patients had both interviews and visual acuity measurements at 12 and 24 months after enrollment. Changes in the overall NEI-VFQ score and in 9 of the subscales (near activities, dependency, driving, role difficulties, distance activities, mental health, general vision, peripheral vision, and social functioning) were related to changes in visual acuity of the better-seeing eye based on linear regression analysis (P<.05). In our analysis, a 3-line decrease in the visual acuity of the better-seeing eye was associated with 3.6- to 16.2-point decreases in the overall NEI-VFQ score and 9 subscale scores. CONCLUSIONS: Most of the NEI-VFQ subscales were responsive to changes in the visual acuity of the better-seeing eye over a 12-month interval in this patient population. Thus, the NEI-VFQ can be used to measure change in vision-targeted quality of life over time to augment clinical measurements of visual acuity.

Dong LM, Hawkins BS, Marsh MJ. · Wilmer Clinical Trials and Biometry, 550 N Broadway, Ninth Floor, Baltimore, MD 21205-2010, USA. · Arch Ophthalmol. · Pubmed #12427067 No free full text.

Abstract: OBJECTIVE: To investigate the consistency of visual acuity (VA) scores measured at 2 different distances in patients with or at risk for choroidal neovascularization. METHODS: Best-corrected VA scores measured at 2 distances for the same eyes at the same examinations were collected from 4 sets of randomized clinical trials among patients with or at risk of choroidal neovascularization. Within each trial, the pairs of VA scores were compared and their relationship was explored. RESULTS: After adjustment for test distance, VA scores obtained at the closer distance were found to be systematically lower than those obtained at the farther distance in all data sets. In the Submacular Surgery Trials pilot study, the average discrepancy between 2- and 0.5-m VA scores was 7.5 letters. In an ancillary study of the Macular Photocoagulation Study, the discrepancy between 10-ft and 5-ft VA scores was 3.1 letters. In the Laser to Drusen Trial pilot study, the discrepancy between 3.2- and 1-m VA scores was 7.3 letters. In the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy Study, in which the VA scores at the closer test distance were censored, the estimated discrepancy between 2- and 1-m VA scores was 8.2 letters. Reduction in visual angle at closer test distance did not explain the discrepancy completely. Features of the macular lesion, poor accommodation of the elderly population with age-related macular degeneration, or the test charts did not account for the discrepancies. CONCLUSION: The VA scores at distances less than 2 m were lower than expected in all 4 studies. The observed discrepancy was consistent with findings from a study among healthy young subjects, suggesting that the phenomenon is real and common.

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.

Orr PR, Marsh MJ, Hawkins BS, Hawse PL, Bressler NM, Anonymous00177. · The Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2010, USA. · Ophthalmic Epidemiol. · Pubmed #15848920 No free full text.

Abstract: PURPOSE: To describe methods and results and to assess the value of a Traveling Vision Examiner (TVE) Program designed to provide masked vision measurements by expert vision examiners who were independent of, and traveled to, local clinical centers. METHODS: The Submacular Surgery Trials (SST) Pilot Study was conducted to refine the design and methods for a set of multicenter, randomized clinical trials to evaluate submacular surgery in patients with subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) or ocular histoplasmosis (OHS), or idiopathic CNV in which the primary study outcome would be change in 2-year best-corrected vision from baseline. As part of the SST Pilot Study, the feasibility and value of a TVE Program was assessed. The goal of the program was to obtain unbiased vision measurements, according to a standard protocol, of best-corrected visual acuity, reading speed, and contrast threshold, of each patient at 2 and 4 years after enrollment. RESULTS: Eighty-three visits by TVEs were made to 16 centers participating in the SST Pilot Study; 239 patients had at least one masked vision examination. Comparison of pairs of vision measurements of the traveling vision examiners and local vision examiners for 71 patients made on the same day showed good agreement overall (intraclass correlation coefficient > or = 0.81). CONCLUSIONS: The proposed TVE Program was judged to be a feasible and useful method of providing standardized, unbiased, masked vision measurements. This approach was incorporated into the larger clinical trials conducted by the SST Research Group.

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.