Macular Degeneration: Bressler NM

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. · No affiliation provided · Am J Ophthalmol. · Pubmed #11755871 No free full text.

This publication has no abstract.

Bressler NM, Anonymous00257. · No affiliation provided · Arch Ophthalmol. · Pubmed #11176980 No free full text.

Abstract: OBJECTIVE: To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, Ga) in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD). DESIGN: Two multicenter, double-masked, placebo-controlled, randomized clinical trials. SETTING: Twenty-two ophthalmology practices in Europe and North America. PARTICIPANTS: Patients with subfoveal CNV lesions caused by AMD with greatest linear dimension on the retina measuring 5400 micrometer or less, with evidence of classic CNV and best-corrected visual acuity (approximate Snellen equivalent) between 20/40 and 20/200. METHODS: The methods were similar to those described in our 1-year results, with follow-up examinations beyond 1 year continuing every 3 months (except for Photograph Reading Center evaluations, which occurred only at month 18 and month 24 examinations). During the second year, the same regimen (with verteporfin or placebo as applied at baseline) was used if angiography showed fluorescein leakage from CNV. The primary outcome was the proportion of eyes with fewer than 15 letters (approximately 3 lines) of visual acuity loss at the month 24 examination, adhering to an intent-to-treat analysis. The last observation was carried forward to impute for any missing data. RESULTS: Three hundred fifty-one (87%) of 402 patients in the verteporfin group compared with 178 (86%) of 207 patients in the placebo group completed the month 24 examination. Beneficial outcomes with respect to visual acuity and contrast sensitivity noted at the month 12 examination in verteporfin-treated patients were sustained through the month 24 examination. At the month 24 examination for the primary outcome, 213 (53%) of 402 verteporfin-treated patients compared with 78 (38%) of 207 placebo-treated patients lost fewer than 15 letters (P<.001). In subgroup analyses for predominantly classic lesions (in which the area of classic CNV makes up at least 50% of the area of the entire lesion) at baseline, 94 (59%) of 159 verteporfin-treated patients compared with 26 (31%) of 83 placebo-treated patients lost fewer than 15 letters at the month 24 examination (P<.001). For minimally classic lesions (in which the area of classic CNV makes up <50% but >0% of the area of the entire lesion) at baseline, no statistically significant differences in visual acuity were noted. Few additional photosensitivity adverse reactions and injection site adverse events were associated with verteporfin therapy in the second year of follow-up. CONCLUSIONS: The visual acuity benefits of verteporfin therapy for AMD patients with predominantly classic CNV subfoveal lesions are safely sustained for 2 years, providing more compelling evidence to use verteporfin therapy for these cases. For AMD patients with subfoveal lesions that are minimally classic, there is insufficient evidence to warrant routine use of verteporfin therapy.

Orr PR, Cramer LD, Hawkins BS, Bressler NM. · The Johns Hopkins University School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205-2010, USA. · Invest Ophthalmol Vis Sci. · Pubmed #11157881 links to  free full text

Abstract: PURPOSE: To compare the results from manifest refraction using trial lenses and a standard visual acuity protocol to results from autorefraction for obtaining refractive error and best corrected visual acuity in patients enrolled in a randomized clinical trial. METHODS: During a 4-month period, 29 patients with subfoveal choroidal neovascularization (CNV), who were enrolled in the Submacular Surgery Trials (SSTs) Pilot Study at the Wilmer Ophthalmological Institute, gave verbal consent to participate in this study. Best corrected visual acuity was obtained using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts and standardized room lighting after performance of manifest refraction, according to the SST protocol, and autorefraction. Refractive error (spherical equivalent) and visual acuity scores were obtained in both eyes of all patients. RESULTS: On average, manifest refraction gave a spherical equivalent that was 1.04 D more plus than autorefraction (95% limits of agreement = 0.74, 1.34). On average, the visual acuity score was 1.5 letters better after manifest refraction than after autorefraction (95% limits of agreement = 0, 3.0).The comparison of the two methods of refraction was subdivided according to visual acuity level and eye disease (age-related macular degeneration or ocular histoplasmosis syndrome). CONCLUSIONS: Despite large differences in spherical equivalent between manifest refraction and autorefraction, the visual acuity scores were close (mean difference, 1.5 letters). Other studies comparing subjective refraction and autorefraction have shown similar results. Autorefraction in patients with subfoveal CNV may be a satisfactory alternative to manifest refraction in clinical trials and field studies in which best corrected visual acuity is of interest.

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.

Sickenberg M, Schmidt-Erfurth U, Miller JW, Pournaras CJ, Zografos L, Piguet B, Donati G, Laqua H, Barbazetto I, Gragoudas ES, Lane AM, Birngruber R, van den Bergh H, Strong HA, Manjuris U, Gray T, Fsadni M, Bressler NM. · Hopital Ophtalmique Jules Gonin, Lausanne, Switzerland. · Arch Ophthalmol. · Pubmed #10721954 No free full text.

Abstract: OBJECTIVE: To evaluate short-term safety and the effects on visual acuity and fluorescein angiography of single or multiple sessions of photodynamic therapy with verteporfin for choroidal neovascularization (CNV) not related to age-related macular degeneration (AMD), including pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes. DESIGN: A nonrandomized, multicenter, open-label, dose-escalation phase 1 and 2 clinical trial. SETTING: Four ophthalmic centers in Europe and North America providing retinal care. PARTICIPANTS: Thirteen patients with subfoveal CNV due to pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, or idiopathic causes. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of photodynamic therapy treatments with verteporfin. Follow-up ranged from 12 weeks for patients who were treated once to 43 weeks for patients who were treated up to 4 times. RESULTS: Verteporfin therapy was well tolerated in patients with CNV not related to AMD. No deterioration in visual acuity was observed; most patients gained at least 1 line of vision. Reduction in the size of leakage area from classic CNV was noted in all patients as early as 1 week after verteporfin therapy, with complete absence of leakage from classic CNV in almost half of the patients. Improvement in visual acuity after verteporfin therapy was greatest (+6, +8, and +9 lines) in 3 patients with relatively poor initial visual acuity (between 20/200 and 20/800). Up to 4 treatments were found to have short-term safety even with retreatment intervals as short as 4 weeks. CONCLUSIONS: Treatment of CNV not related to AMD with verteporfin therapy achieves short-term cessation of fluorescein leakage from CNV in a small number of patients without loss of vision. Further randomized clinical trials including a larger number of patients are under way to confirm whether verteporfin therapy is beneficial for subfoveal CNV not related to AMD.

Schmidt-Erfurth U, Miller JW, Sickenberg M, Laqua H, Barbazetto I, Gragoudas ES, Zografos L, Piguet B, Pournaras CJ, Donati G, Lane AM, Birngruber R, van den Berg H, Strong HA, Manjuris U, Gray T, Fsadni M, Bressler NM. · Retina Department, University Eye Hospital, Lübeck, Germany. · Arch Ophthalmol. · Pubmed #10496389 No free full text.

Abstract: OBJECTIVES: To evaluate safety and short-term visual acuity and fluorescein angiographic effects of photodynamic therapy (PDT) after retreatments with verteporfin for choroidal neovascularization (CNV) in age-related macular degeneration (AMD) that demonstrated fluorescein leakage after at least 1 course of PDT. DESIGN: Nonrandomized, multicenter, open-label phase 1 and 2 clinical trial using 2 different retreatment dosage regimens. SETTING: Four ophthalmic centers in Europe and North America providing retinal care. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of multiple PDT treatments. Two regimens (regimens 2 and 4) for treatment and retreatment were chosen from 5 used in a single-treatment study. Both regimens used a verteporfin dose of 6 mg/m2 infused for 10 minutes. However, regimen 2 used a light dose of 100 J/cm2 applied 20 minutes after the start of the verteporfin infusion, whereas regimen 4 used a light dose of 50, 75, or 100 J/cm2 applied 15 minutes after infusion commenced. Posttreatment evaluations were planned in 31 participants up to 3 months after up to 2 retreatments given at 2- or 4-week intervals after initial PDT treatment. Similar posttreatment evaluations were planned after retreatments in 5 additional participants who were reenrolled some time more than 12 weeks after an initial PDT treatment. RESULTS: The average visual acuity change for the 31 participants who had retreatment within 2 to 4 weeks after the initial treatment and a follow-up examination 16 to 20 weeks after the initial treatment was 0.2 lines (range, -4 to 4 lines) in regimen 2 and -1.0 line (range, -5 to 3 lines) in regimen 4. Similar outcomes were noted in the 5 reenrolled participants. Cessation of fluorescein leakage from classic CNV for at least 1 to 4 weeks could be achieved without loss of visual acuity after at least 2 treatments in 2 (6.5%) of 31 patients. Similar to single-treatment effects, the disappearance of leakage was documented regularly at 1 week after each retreatment. Fluorescein leakage reappeared by 4 to 12 weeks after a retreatment in almost all cases. However, compared with baseline, leakage activity appeared to be reduced after multiple PDT courses. For the 31 patients who had follow-up for 3 months after the last retreatment and had received retreatment 2 to 4 weeks after the initial treatment, progression of CNV beyond the area identified before the retreatment was noted in 10 (48%) of the 21 eyes with classic CNV in regimen 2 and 9 (90%) of 10 eyes in regimen 4. The rate and severity of ocular or systemic adverse events were not increased by multiple applications. CONCLUSIONS: Multiple applications of PDT with verteporfin achieve repetitive, short-term cessation of fluorescein leakage from CNV secondary to AMD, without loss of visual acuity. This strategy can be used in randomized clinical trials investigating the efficacy of verteporfin in PDT for recurrent fluorescein dye leakage from persistent or recurrent CNV, following an initial or subsequent PDT treatment, with maintenance of visual acuity. Retreatments may achieve progressive cessation of leakage and prevent further growth of CNV and subsequent visual loss.

Miller JW, Schmidt-Erfurth U, Sickenberg M, Pournaras CJ, Laqua H, Barbazetto I, Zografos L, Piguet B, Donati G, Lane AM, Birngruber R, van den Berg H, Strong A, Manjuris U, Gray T, Fsadni M, Bressler NM, Gragoudas ES. · Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, USA. · Arch Ophthalmol. · Pubmed #10496388 No free full text.

Abstract: OBJECTIVE: To evaluate the safety and short-term visual and fluorescein angiographic effects of a single photodynamic therapy treatment with verteporfin with the use of different dosage regimens in patients with choroidal neovascularization (CNV) from age-related macular degeneration. DESIGN: Nonrandomized, multicenter, open-label, clinical trial using 5 dosage regimens. SETTING: Four ophthalmic centers in North America and Europe providing retinal care. PARTICIPANTS: Patients with subfoveal CNV caused by age-related macular degeneration. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examination, color photographs, and fluorescein angiograms were used to evaluate the effects of a single treatment of photodynamic therapy with verteporfin. Follow-up was planned through 3 months in 97 patients and for less than 3 months in 31 other patients. RESULTS: The mean visual acuity change (and range of change) from baseline at the follow-up examination at week 12 after a single treatment with regimens 1 through 5 was -0.2 (-3 to +2), -0.9 (-9 to +5), -1.6 (-9 to +2), +0.4 (-8 to +7), and +0.1 (-8 to +9) lines, respectively. Only the highest light dose (150 J/cm2) in regimens 2 and 3, which produced angiographic nonperfusion of neurosensory retinal vessels, caused marked vision loss. Some cessation of fluorescein leakage from CNV was achieved without loss of vision when the light dose used was less than 150 J/cm2. Systemic adverse events were rare. Cessation of fluorescein leakage from CNV was noted in all regimens by 1 week after photodynamic therapy. Fluorescein leakage from at least a portion of the CNV reappeared by 4 to 12 weeks after treatment in almost all cases. Progression of classic CNV beyond the area of CNV identified before treatment was noted in 42 (51%) of the 83 eyes with classic CNV followed up for 3 months after a single treatment. Eyes in which the area of any CNV leakage at 12 weeks was less than at baseline had a significantly better visual acuity outcome (+0.8 line) than eyes in which CNV leakage progressed (-0.8 line). CONCLUSIONS: Photodynamic therapy with verteporfin achieved short-term cessation of fluorescein leakage from CNV without loss of vision or growth of classic CNV in some patients with age-related macular degeneration. Except for nonperfusion of neurosensory retinal vessels at a light dose of 150 J/cm2, no other adverse events were of concern. Randomized clinical trials to investigate whether this new modality can preserve vision in patients with CNV secondary to age-related macular degeneration are justified.

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.

Solomon SD, Dong LM, Haller JA, Gilson MM, Hawkins BS, Bressler NM, Anonymous00207. · Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Retina. · Pubmed #19516120 No free full text.

Abstract: OBJECTIVE: To identify risk factors associated with the development of rhegmatogenous retinal detachment (RRD) in patients enrolled in the Submacular Surgery Trials. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Hawkins BS, Bressler NM, Reynolds SM. · Wilmer Eye Institute, School of Medicine, Johns Hopkins University, 550 N Broadway, Room 930, Baltimore, MD 21205-2010, USA. · Arch Ophthalmol. · Pubmed #19506188 No free full text.

Abstract: OBJECTIVE: To compare 2-year visual acuity outcomes between similar participants assigned to sham and no-treatment control arms in randomized clinical trials. METHODS: We retrospectively matched sham controls from 2 randomized trials to no-treatment controls (no sham or placebo) from 3 trials on 8 baseline prognostic criteria (full matches) or on 4 to 7 criteria (partial matches). Outcomes were compared using data from those who had 2-year visual acuity measurements and also using the last observation carried forward method to impute missing 2-year measurements. RESULTS: A full match to a no-treatment control was identified for 72 of 321 sham controls (22%); a partial match was identified for another 93 sham controls (29%). Among the fully matched pairs, no important difference in 2-year visual acuity outcomes was observed. However, 2-year outcomes differed somewhat between sham and no-treatment controls within the partially matched pairs. CONCLUSIONS: Findings from fully matched pairs suggest that sham treatment to mask participants in clinical trials may be unnecessary when visual acuity is the outcome of interest. However, findings from the partially matched pairs do not fully support this conclusion. This analysis challenges the necessity for sham (placebo) controls in randomized clinical trials in ophthalmology when visual acuity is the primary outcome of interest.

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.

Anonymous00065, Beck RW, Edwards AR, Aiello LP, Bressler NM, Ferris F, Glassman AR, Hartnett E, Ip MS, Kim JE, Kollman C. · No affiliation provided · Arch Ophthalmol. · Pubmed #19273785 No free full text.

Abstract: OBJECTIVE: To report 3-year outcomes of patients who participated in a randomized trial evaluating 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone compared with focal/grid photocoagulation for treatment of diabetic macular edema. METHODS: Eyes with diabetic macular edema and visual acuities of 20/40 to 20/320 were randomly assigned to focal/grid photocoagulation or 1 mg or 4 mg of triamcinolone. At the conclusion of the trial, 3-year follow-up data were available in 306 eyes. RESULTS: Between 2 years (time of the primary outcome) and 3 years, more eyes improved than worsened in all 3 treatment groups. Change in visual acuity letter score from baseline to 3 years was +5 in the laser group and 0 in each triamcinolone group. The cumulative probability of cataract surgery by 3 years was 31%, 46%, and 83% in the laser and 1-mg and 4-mg triamcinolone groups, respectively. Intraocular pressure increased by more than 10 mm Hg at any visit in 4%, 18%, and 33% of eyes, respectively. CONCLUSIONS: Results in a subset of randomized subjects who completed the 3-year follow-up are consistent with previously published 2-year results and do not indicate a long-term benefit of intravitreal triamcinolone relative to focal/grid photocoagulation in patients with diabetic macular edema similar to those studied in this clinical trial. Most eyes receiving 4 mg of triamcinolone as given in this study are likely to require cataract surgery. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00367133.

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.

Jefferys JL, Alexander J, Hiner CJ, Javornik NB, Smith RE, Bressler NM, Hawkins BS. · The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Ophthalmic Epidemiol. · Pubmed #18569815 No free full text.

Abstract: PURPOSE: To assess the reproducibility of the evaluation of color photographs and fluorescein angiograms of the macula of each eye for patients enrolled in the Macular Photocoagulation Study (MPS) trials of laser photocoagulation of subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration. METHODS: A total of 65 pre-enrollment and 26 posttreatment sets of photographs were regraded. The two gradings were compared on selected items judged to be of primary importance with respect to the role of the MPS Reading Center. RESULTS: Agreement on eligibility of the neovascular lesion for an MPS trial was 88% (kappa statistic = 0.59); agreement on the size of the lesion was 86% (kappa statistic = 0.80); agreement on whether the lesion was covered by heavy treatment was 69% (kappa statistic = 0.35); and agreement on whether the treatment was in compliance with the study protocol was 73% (kappa statistic = 0.06). CONCLUSIONS: Interpretation of photographs of eyes with CNV secondary to age-related macular degeneration for eligibility and size of the lesion was reproducible in the MPS. However, adequacy of laser photocoagulation treatment could not be determined reliably from photographs.

Kim SJ, Belair ML, Bressler NM, Dunn JP, Thorne JE, Kedhar SR, Jabs DA. · Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA 30322, USA. · Retina. · Pubmed #18536605 No free full text.

Abstract: OBJECTIVE: To validate a method of reporting postcataract macular edema (ME) using optical coherence tomography (OCT). METHODS:: Data were analyzed for 130 eyes followed prospectively for ME after uncomplicated cataract surgery. Each eye underwent OCT within 4 weeks before surgery and at 1 month and 3 months after surgery. ME was defined by observation of cystoid changes by OCT. RESULTS: Incidence of ME was 14% (95% confidence interval, 8-20). Average increase in baseline center point thickness (CPT) +/- SD at 1 month for eyes with and without ME was 202 +/- 113 microm and 8 +/- 19 microm, respectively (P < 0.001), which resulted in a 1-letter loss (-0.02 logMAR [logarithm of the minimum angle of resolution]) and a 3-line gain (0.29 logMAR) in vision, respectively (P < 0.001). Percent change in baseline CPT +/- SD for eyes with and without ME was 115 +/- 67% and 6 +/- 11%, respectively (P < 0.001). A > or =40% increase in baseline CPT accurately determined 100% of eyes with ME and 99% of eyes without ME. CONCLUSIONS: A > or =40% increase in baseline CPT, determined by OCT, offers a valid and objective method of reporting clinically relevant postcataract ME. Standardized reporting of postcataract ME would allow objective assessment and comparison of treatment outcomes among clinical studies.

Sunness JS, Rubin GS, Broman A, Applegate CA, Bressler NM, Hawkins BS. · The Richard E Hoover Rehabilitation Services for Low Vision and Blindness, Greater Baltimore Medical Center, Baltimore, Maryland 21204, USA. · Ophthalmology. · Pubmed #18486216 No free full text.

Abstract: OBJECTIVE: To show that low luminance visual dysfunction is predictive of subsequent visual acuity (VA) loss in eyes with geographic atrophy (GA) resulting from age-related macular degeneration (AMD). DESIGN: Cohort study examining the prospective natural history study of GA from 1992 through 2000 at the Wilmer Eye Institute. PARTICIPANTS: Ninety-one participants with GA resulting from AMD without choroidal neovascularization in at least 1 eye who completed a 2-year study examination. METHODS: Annual examinations included measurement of best-corrected VA, low luminance VA, Pelli-Robson contrast sensitivity, reading speed, examination, and fundus photography. The total GA area was quantified, as was the GA within a 10.2-mm(2) circle centered on the fovea. MAIN OUTCOME MEASURES: Visual acuity loss at 2 years and risk factors for visual loss. RESULTS: Participants with baseline VA of 20/50 or more had a 40% 2-year rate of VA loss of 3 lines or more, compared with 13% for the participants with worse baseline acuities. The baseline low-luminance deficit (LLD) in VA was a strong predictor of subsequent VA loss for all levels of baseline VA. Within the good baseline VA group, the relative risk (RR) of 3-line loss for the worse LLD group compared with the better LLD group was 2.88 (95% confidence interval [CI], 1.13-7.35). The LLD is a stable and reproducible measure. Other significant visual function predictors of subsequent VA loss in eyes with good baseline VA included foveal dark-adapted sensitivity (RR, 4.20; 95% CI, 1.39-12.71) and reduced reading rate (RR, 2.43; 95% CI, 1.11-5.31). The rate of VA loss within the good acuity group was higher when the GA included 25% to 75% of the central 10.2 mm(2) than in eyes with GA including less than 25% or more than 75% of the central 10.2 mm(2). The following were not significant predictors of subsequent VA loss among these participants: age, gender, fellow eye diagnosis, fellow eye VA, baseline GA area, and GA enlargement rate. CONCLUSIONS: Visual function measures can predict the risk of future VA loss in subjects with GA and good baseline VA. They may allow identification of the highest risk group for VA loss, enabling more efficient design of clinical trials. They also may be appropriate surrogate measures of foveal health in short-term treatment trials.

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.

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.

Chang TS, Bressler NM, Fine JT, Dolan CM, Ward J, Klesert TR, Anonymous00144. · Retina Institute of California, 800 S Fairmount Ave, Ste 312, Pasadena, CA 91105, USA. · Arch Ophthalmol. · Pubmed #17998507 links to  free full text

Abstract: OBJECTIVE: To examine the effects of ranibizumab on patient-reported visual function using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) in patients with neovascular age-related macular degeneration (AMD). DESIGN: In MARINA, a randomized, double-masked clinical trial, 716 patients with AMD with recent disease progression and minimally classic or occult with no classic lesion component were randomized 1:1:1 to monthly intravitreal ranibizumab (0.3 or 0.5 mg) or sham injections. The NEI VFQ-25 was administered at 0, 1, 2, 3, 6, 9, 12, 18, and 24 months. Main Outcome Measure Mean change from baseline in NEI VFQ-25 scores at 12 and 24 months. RESULTS: At 12 months, ranibizumab-treated patients (0.3 mg [n = 238] and 0.5 mg [n = 240]) had mean improvements in NEI VFQ-25 composite scores of +5.2 (95% confidence interval [CI], 3.5 to 6.9) and +5.6 (95% CI, 3.9 to 7.4), respectively; sham-injected patients (n = 238) had a mean decline of -2.8 (95% CI, -4.6 to -1.1; P < .001 vs each dose). Ranibizumab-treated patients were more likely to improve in near activities, distance activities, and vision-specific dependency through 24 months. CONCLUSIONS: In MARINA, ranibizumab-treated patients were more likely than sham-treated patients to report visual function improvements at 12 and 24 months. APPLICATION TO CLINICAL PRACTICE: Treatment of neovascular AMD with ranibizumab can improve patient-reported visual function in a meaningful way compared with sham treatments. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00056836.

Anonymous00076, Solomon SD, Jefferys JL, Hawkins BS, Bressler NM. · Johns Hopkins University School of Medicine, 550 N Broadway, Ste 115, Baltimore, MD 21205-2005, USA. · Arch Ophthalmol. · Pubmed #17923538 links to  free full text

Abstract: OBJECTIVE: To describe incident choroidal neovascular lesions in fellow eyes of participants in the Submacular Surgery Trials who had age-related macular degeneration (AMD). METHODS: 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. MAIN OUTCOME MEASURES: Incidence of CNV during follow-up, characteristics of the incident lesion (composition, size, and location), and visual acuity at the time of incidence. RESULTS: 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.

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

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

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

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

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

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