Submacular Surgery Trials Research Articles

Visual function quality of life measure changes upon conversion to neovascular age-related macular degeneration in second eyes.

To determine changes in quality of life measures when choroidal neovascularization (CNV) developed in the second eye of patients with initially unilateral neovascular age-related macular degeneration (AMD). We analyzed responses to the 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ), 36-item Short Form Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HADS) at baseline, and prior to and following second eye CNV diagnosis in 92 participants enrolled in two Submacular Surgery Trials. Paired t-tests for sample sizes over 30 and Wilcoxon signed-rank tests for sample sizes <30 were performed to compare scores. CNV development resulted in statistically and clinically significant changes in responses to 20 of 39 NEI-VFQ items, indicating visual function decline during a mean interval of 25 months. Little difference was noted between baseline scores and prior to CNV diagnosis, which averaged 8.9 months duration. Subscales demonstrated a statistically significant decline in general vision, near activities, distance activities, social functioning, role difficulties, dependency, and driving. There were minimal changes in the HADS and SF-36 scales. CNV development in the second eye had a dramatic effect on visual functioning based on patient responses to the NEI-VFQ questionnaire. Our investigation is believed to be the first study using data collected prospectively to demonstrate vision-related quality of life changes that resulted from development of CNV in AMD patients.

A multilevel refraction protocol based on visual acuity

Objective: To describe the historical development and methodology of a standard subjective refraction protocol to obtain best-corrected visual acuities in multicentre ophthalmic clinical trials. Methods: A revised, multilevel, subjective refraction protocol was developed for the Macular Photocoagulation Study (MPS) to accommodate poorer levels of vision than had previously been encountered. Results: Since its development in 1983, the multilevel refraction protocol has been adopted by several major clinical trials, is a reliable method to obtain best-corrected visual acuity among patients with a wide range of visual acuities and eye disorders, and has been shown to be more reliable than autorefraction. Among 82 participants in the MPS, 89% of repeated refractions obtained using the multilevel refraction protocol differed from each other by less than +/– 0.50 dioptre (D) and 97.5% by less than +/–1.00 D. Among 29 participants in the Submacular Surgery Trials (SST), the multilevel refraction protocol gave a spherical equivalent that averaged 1.04 D more positive than autorefraction (95% limits of agreement: 0.74, 1.34), and the visual acuity score, using the refraction protocol, was 1.5 letters better compared with autorefraction (95% limits of agreement: 0.0, 3.0). Conclusions: The multilevel refraction protocol is a reliable method of obtaining best-corrected visual acuity among patients across a wide range of visual acuities and many different eye disorders in ophthalmic clinical trials.

Sub-Macular Surgery: Is Still an Option for Age-Related Macular Degeneration?

This review summarizes the data reported in peer-reviewed literature on the effects of submacular surgery for age-related macular degeneration (AMD) associated with choriodal neovascularization (CNV). A review of the MEDLINE database has been performed in order to examine the therapeutic effects of submacular surgical treatments in patients affected by AMD. The multicenter studies conducted by the Submacular Surgery Trials Research Group compare the removal of the CNV complex, both with (336) and without blood (454), with observation in patients affected by AMD. At a 1-year follow-up, no benefit in preventing visual loss had been shown. Furthermore, complications occurred in the surgery arm such as retinal detachment and lens opacification. No differences have been found between submacular surgery and laser photocoagulation in terms of visual acuity and quality of life. As yet, there are no randomized controlled trials concerning retinal pigment epithelium and choroid translocation or macular translocation, but only prospective, non-controlled case series with low quality of evidence. No evidence of potential benefit from submacular removal of the CNV complex due to AMD has been shown. Randomized clinical trails (RCT) concerning other submacular surgical approaches are not available. There are sufficient non-comparative data on retinal pigment epithelium (RPE) graft to warrant an RCT especially in patients with large subretinal haemorrhages, RPE rip or in Anti-VEGF non-responders.

PROSPECTIVE ONE-YEAR STUDY OF RANIBIZUMAB FOR PREDOMINANTLY HEMORRHAGIC CHOROIDAL NEOVASCULAR LESIONS IN AGE-RELATED MACULAR DEGENERATION

To determine the safety and effect of ranibizumab on predominantly hemorrhagic choroidal neovascular lesions due to age-related macular degeneration. Seven subjects with predominantly hemorrhagic choroidal neovascular lesions were treated with intravitreal injections of ranibizumab at baseline, Month 1, and Month 2. Additional monthly injections were given through Month 11 at the discretion of the examiner for a potential maximum of 12 injections. At 12 months, the median visual acuity letter score was 30 (Snellen equivalent: 20/250), with a median change from baseline to last follow-up of +7 letters. Three of 7 subjects (43%) gained 2 or more lines of vision, while no subject lost 2 or more lines. The median change in OCT central subfield thickness from baseline to Month 12 was -109 microm, with a mean of -120 +/- 158 microm. Two eyes had retinal pigment epithelial tears. No ocular adverse events or systemic adverse events were reported related to the usage of ranibizumab. With no subject losing 2 or more lines of visual acuity over 12 months and no new safety concerns identified, these predominantly hemorrhagic lesions treated with ranibizumab appeared to have a better visual acuity outcome than the natural history controls of the submacular surgery trials. While the study is limited by few cases enrolled, the results suggest that ranibizumab is able to penetrate through the subretinal hemorrhage to affect the underlying hemorrhagic choroidal neovascular lesion and the natural history.

RISK FACTORS FOR SECOND EYE PROGRESSION TO ADVANCED AGE-RELATED MACULAR DEGENERATION

To identify characteristics predictive of progression to advanced age-related macular degeneration (AMD) in second (fellow) eyes of participants in the Submacular Surgery Trials (SST) who had unilateral neovascular AMD at study entry. Review of baseline fluorescein angiograms confirmed the absence of advanced AMD in 370 fellow eyes. All participants were eligible for 2 years of follow-up; follow-up angiograms of eyes at risk were evaluated to estimate incidence rates of advanced AMD. Baseline nonocular and ocular AMD characteristics were evaluated to identify those that predicted development of advanced AMD. Of 110 eyes that progressed to advanced AMD, choroidal neovascularization (CNV) developed in 98 eyes and foveal geographic atrophy (GA) in 15 eyes. No nonocular characteristic (age, gender, history of hypertension or smoking) or ocular feature of the study eye at baseline (lesion composition, lesion size, or visual acuity) was predictive of progression to advanced AMD in this cohort. Multivariate analysis identified three baseline fellow eye ocular features that had a significant and independent relationship with progression to advanced AMD: drusen size, focal hyperpigmentation, and nonfoveal GA. Recognition of factors that predict advanced AMD in the second eye may identify those individuals at greater risk of progression so that treatment can be provided before vision is severely compromised.

RISK FACTORS FOR RHEGMATOGENOUS RETINAL DETACHMENT IN THE SUBMACULAR SURGERY TRIALS

To identify risk factors associated with the development of rhegmatogenous retinal detachment (RRD) in patients enrolled in the Submacular Surgery Trials. One thousand fifteen patients with eligible subfoveal neovascular lesions in the study eye were assigned randomly to observation or to surgery. Eyes were examined at 3 months, 6 months, 12 months, and 24 months after enrollment to assess study outcomes and adverse events, including RRDs. Adverse events also were reported at other times as clinical personnel became aware of them. Potential risk factors for the development of RRD in study eyes were evaluated using recursive partitioning and logistic regression analysis. Among 506 eyes assigned to surgery, RRD developed in 44 (8.7%) compared with 4 (0.8%) of 509 eyes assigned to observation. Of the 44 eyes in which RRD developed, 27 had age-related macular degeneration (AMD) and large (>3.5 MPS disk areas) hemorrhagic subfoveal neovascular lesions at baseline and represented 16.1% of all eyes with such lesions assigned to surgery. Eyes with AMD and larger hemorrhagic lesions (>16 MPS disk areas) together with relatively poor visual acuity (best-corrected visual acuity < or =20/1280) had a higher risk of RRD (odds ratio = 6.2, 95% confidence interval: 2.2-16.7) compared with those with smaller lesions and better visual acuity at baseline. Poor visual acuity and very large, predominantly hemorrhagic subfoveal neovascular AMD lesion type were the greatest risk factors for RRD after submacular surgery. Submacular surgery should be undertaken in such eyes with full awareness of the risk of RRD during subsequent follow-up.

Surgical Removal vs Observation for Idiopathic or Ocular Histoplasmosis Syndrome–Associated Subfoveal Choroidal Neovascularization

To determine whether patients receiving observation vs surgery for subfoveal choroidal neovascularization that was idiopathic or associated with histoplasmosis differed in preference values assigned to their health and vision status. Before and after enrollment, patients rated their current vision on a scale from 0 (blind) to 100 (perfect vision) and rated blindness and perfect vision on a scale from 0 (dead) to 100 (perfect health and vision). Scores for current vision were converted to a preference value scale (0 represents death; 100, perfect health and vision). In 170 patients, no significant difference existed between the observation and surgery arms in median vision preference values at baseline (74 vs 70) or at the 12- (74 vs 78) or 24-month follow-up (77 vs 73) (P > .05). Preference values did not differ between arms for subgroups defined by age, unilateral vs bilateral choroidal neovascularization, or good vs poor baseline visual acuity. Submacular surgery was no better than observation in the preference values patients assigned to their health status, despite previously reported improvements in vision-specific quality of life. (clinicaltrials.gov) Identifier: NCT00000150. Ophthalmologists should consider the effects on different measures of quality of life when determining treatment for patients similar to those in the Submacular Surgery Trials Group H Trial.

Incident choroidal neovascularization in fellow eyes of patients with unilateral subfoveal choroidal neovascularization secondary to age-related macular degeneration: SST report No. 20 from the Submacular Surgery Trials Research Group

Incident choroidal neovascularization in fellow eyes of patients with unilateral subfoveal choroidal neovascularization secondary to age-related macular degeneration: SST report No. 20 from the Submacular Surgery Trials Research Group

Incident Choroidal Neovascularization in Fellow Eyes of Patients With Unilateral Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration

To describe incident choroidal neovascular lesions in fellow eyes of participants in the Submacular Surgery Trials who had age-related macular degeneration (AMD). Review of baseline fluorescein angiograms confirmed the absence of neovascular AMD in fellow eyes of 364 participants at risk. Subjects were eligible for a minimum of 2 years of follow-up with angiograms of eyes at risk reevaluated to estimate incidence rates of choroidal neovascularization (CNV) and to characterize these lesions. Incidence of CNV during follow-up, characteristics of the incident lesion (composition, size, and location), and visual acuity at the time of incidence. Incident lesions were confirmed in 98 fellow eyes of participants, yielding 2- and 4-year cumulative incidence rates of 22% and 37%. Incident lesions were predominantly CNV in 87 fellow eyes (90%), extrafoveal in 29 fellow eyes (30%), and juxtafoveal in 9 fellow eyes (9%). Occult without classic CNV lesions were found in 64 eyes (67%), minimally classic CNV and predominantly classic CNV lesions in 12 eyes (13%) each, and predominantly blood lesions in 4 eyes (4%). Nearly two-thirds of all incident lesions were 3 disc areas or smaller in size. Median visual acuity decreased from 20/25 at baseline to 20/250 at the 4-year follow-up in fellow eyes with incident CNV. CONCLUSIONS AND APPLICATION TO CLINICAL PRACTICE: Frequent angiographic follow-up of fellow eyes at risk for CNV may lead to earlier detection and treatment of neovascular AMD and better visual acuity outcomes.

PATIENTS’ PREFERENCES IN CHOOSING THERAPY FOR RETINAL VEIN OCCLUSIONS

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. 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. 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. 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.

Comparison of Methods to Identify Incident Cataract in Eyes of Patients with Neovascular Maculopathy: Submacular Surgery Trials Report No. 18

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. Prospective study of patients enrolled in a set of randomized clinical trials. 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. 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. Incidence of cataract in study eyes. 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). 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.

The end of submacular surgery for age-related macular degeneration? A meta-analysis

The aim of this meta-analysis was to summarize and to discuss the results of the four main submacular surgical procedures for age-related macular degeneration (AMD) as reported in the literature through 2004 and to compare them to the Submacular Surgery Trials (SST) data. The existing data in the literature on submacular surgery for AMD from 1992 to 2004 were evaluated. The main outcomes were proportion of patients with two or more lines of improvement in visual acuity (VA) and proportion with two or more lines of deterioration in VA after surgery. Eighty-eight studies including 1,915 cases met the inclusion criteria. Estimates for the treatment outcome within the four groups of treatment based on a logistic regression model gave comparable results for removal of choroidal neovascularization (CNV) (improvement of VA 28%, deterioration of VA 25%), macular translocation (improvement of VA 31%, deterioration of VA 27%), and for transplantation of pigment epithelium (improvement of VA 22%, deterioration of VA 21%). Estimates for removal of subretinal hemorrhage were significantly different (improvement of VA 62%, deterioration of VA 13%). Selected case series showed superior results of VA compared to the SST. The question of whether this is due to selection bias that seems inevitable when dealing with medium-sized nonrandomized case series or due to better results in single centers cannot be answered. In our opinion there still seem to be indications for submacular surgery such as in patients with AMD with low preoperative VA due to large hemorrhagic or fibrotic membranes or nonresponders to photodynamic therapy (PDT).

Comparison of 2D Reconstructions of Surgically Excised Subfoveal Choroidal Neovascularization with Fluorescein Angiographic Features: SST Report No. 15

To compare topographic features of surgically excised subfoveal choroidal neovascularization with preoperative and postoperative fluorescein angiographic features from Submacular Surgery Trials (SST) patients, and to compare histological and angiographic features with preoperative and postoperative visual acuities (VAs). Patients enrolled in the SST Groups N, B, and H trials between October 1999 and September 2001 and assigned to the surgery arm had surgically removed choroidal neovascularization sent to the SST Pathology Center. Grossly intact specimens were sectioned serially for 2-dimensional reconstruction and were assigned to growth pattern groups based on topographic mapping of the location of cellular components relative to the retinal pigment epithelium (RPE): sub-RPE, subretinal, combined, or indeterminate. These features were compared with preoperative fluorescein angiographic features. The histological choroidal neovascularization growth pattern was compared with preoperative VAs. Two-dimensional reconstructions of surgically excised choroidal neovascularization could not be matched point for point to fluorescein angiographic features. Among the 52 specimens selected, the growth pattern could be determined by 2-dimensional reconstruction in 34 instances (65%), including 28 (80%) of 35 Group N specimens, 2 (40%) of 5 Group B specimens, and 4 (33%) of 12 Group H specimens. Among the choroidal neovascularization growth patterns that could be determined from specimens submitted, the majority of Group N specimens were combined, and the majority of Group H specimens were subretinal. In most instances for Group B specimens, the growth pattern was indeterminate. The postoperative abnormalities on fluorescein angiography were generally larger than measurements of excised specimens. The subretinal growth pattern was associated with the smallest decrease in 3-month postoperative average VA. Among the 52 specimens from the SST with adequate tissue to try to evaluate the growth pattern of the neovascular lesion, 34 had patterns that could be determined. The subretinal growth pattern tended to correspond with lesions that were classic choroidal neovascularization without occult choroidal neovascularization on fluorescein angiography. The most favorable visual outcome occurred if the choroidal neovascularization had a subretinal growth pattern. The combined growth pattern tended to correspond with lesions on fluorescein angiography that had both classic choroidal neovascularization and occult choroidal neovascularization. The conclusions must be viewed within the context that 18 (35%) of the 52 participants could not be characterized for histologic growth pattern.

Clinicopathologic Studies of Eyes That Were Obtained Postmortem From Four Patients Who Were Enrolled in the Submacular Surgery Trials: SST Report No. 16

To compare the fundus photographic and fluorescein angiographic features with the histologic findings in eyes from patients enrolled in the Submacular Surgery Trials (SST). Clinical trials with clinicopathologic correlation. 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. 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. 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.

Histopathologic and Ultrastructural Features of Surgically Excised Subfoveal Choroidal Neovascular Lesions

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. 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. 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. 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.

GUIDELINES FOR INTERPRETING RETINAL PHOTOGRAPHS AND CODING FINDINGS IN THE SUBMACULAR SURGERY TRIALS (SST)

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. 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. 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. 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.

Effect of order of administration of health-related quality of life interview instruments on responses

To determine the effect on patient responses from the order in which the generic health-related and vision-targeted instruments are administered in a set of randomized clinical trials of intraocular surgery. Patients who agreed to enroll in the Submacular Surgery Trials (SST) completed baseline quality of life interviews prior to random assignment to surgery or observation. Interviews were conducted by trained interviewers located at the SST Coordinating Center, via a computer-assisted telephone interview system that randomly assigned the order of instrument administration. Either the generic health-related instruments were administered first, the SF-36 Health Survey (SF-36) followed by the Hospital Anxiety and Depression Scale (HADS), followed by the vision-targeted instruments, National Eye Institute-Vision Function Questionnaire (NEI-VFQ) followed by the SST-Vision Preference Value Scale, or the vision-targeted questions were asked first, followed by the generic health instruments. The four instruments have 25 subscales total. Of the 1015 patients enrolled in the SST, 992 patients had all four instruments administered in random order: 483 (49%) patients responded to the generic instruments first and 509 (51%) patients responded to the vision-targeted instruments first. Order of administration produced significantly different scores for three health status subscales: SF-36 mental health, HADS depression and HADS anxiety (p < or = 0.05, Wilcoxon rank sum test). Overall, the order of administration did not have a large effect on responses to the baseline interviews in this study. However, three mental health subscales were affected by order, though the order effect was small in magnitude. When the generic health instruments followed the vision-targeted instrument the HADS depression and anxiety scores were higher and the SF-36 mental health scores were lower, both suggesting poorer mental health status. Thus, the order of administration in other settings in which both a generic health-related instrument and a condition-targeted instrument are used may be decided based on individual study goals and priorities but order of administration should be consistent throughout the study.

Evaluation of the Traveling Vision Examiner Program in the Submacular Surgery Trials Pilot Study

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,≥,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.

Surgical Removal vs Observation for Subfoveal Choroidal Neovascularization, Either Associated With the Ocular Histoplasmosis Syndrome or Idiopathic: I. Ophthalmic Findings From a Randomized Clinical Trial: Submacular Surgery Trials (SST) Group H Trial: SST Report No. 9—Correction

Surgical Removal vs Observation for Subfoveal Choroidal Neovascularization, Either Associated With the Ocular Histoplasmosis Syndrome or Idiopathic: I. Ophthalmic Findings From a Randomized Clinical Trial: Submacular Surgery Trials (SST) Group H Trial: SST Report No. 9—Correction

Patients’ Perceptions of the Value of Current Vision

To improve understanding and awareness of the impact of subfoveal choroidal neovascularization (CNV) on health-related quality of life, we sought to measure the preference value that patients with subfoveal CNV assigned to their health and vision status. Patients with subfoveal CNV completed telephone interviews about their quality of life prior to enrollment and random treatment assignment in the Submacular Surgery Trials, a set of multicenter randomized controlled trials evaluating outcomes of submacular surgery compared with observation. The interviewers asked patients to rate their current vision on a scale from 0 (completely blind) to 100 (perfect vision). The interviewers also asked them to rate complete blindness and then perfect vision, assuming their health otherwise was the same as it was at the time of the interview, on a scale from 0 (dead) to 100 (perfect health with perfect vision). Scores were converted to a 0 to 1 preference value scale for health and vision status, where 0 represents death and 1 represents perfect health and vision. Of 1015 participants enrolled in the Submacular Surgery Trials, 996 completed interviews that included the rating questions, and 792 (80%) answered all 3 rating questions in a manner permitting calculation of a single overall preference value for their current health and vision status on a scale from 0 (dead) to 1 (perfect). The mean preference value was 0.64 (median, 0.68; interquartile range, 0.51-0.80). The preference values correlated with age (Pearson correlation coefficient, -0.11; P = .002), patients' self-rated perception of overall health (Spearman correlation coefficient, 0.36; P<.001), and self-reported perception of vision (Spearman correlation coefficient, 0.47; P<.001). The preference values were significantly lower with poorer visual acuity in the better eye and greater evidence of dysfunction on either the Hospital Anxiety and Depression Scale or the Physical or Mental Component Summary scales of the Short Form-36 Health Survey but did not differ significantly by gender or other baseline characteristics such as race, treatment assignment, or size of the CNV lesion. Vision loss from subfoveal CNV is associated with patient preference values that are as low as or lower than values previously reported for other serious medical conditions such as dialysis-dependent renal failure and AIDS, indicating that both unilateral and bilateral CNV have a profound impact on how patients feel about their overall health-related quality of life.