Macular Degeneration: Blinder KJ

Wickens J, Blinder KJ. · Barnes Retina Institute, Department of Ophthalmology, Washington University School of Medicine, St Louis, Missouri 63144, USA. · Drug Saf. · Pubmed #16524319 No free full text.

Abstract: The prevalence of neovascular age-related macular degeneration (AMD) is expected to increase significantly during the next 20 years. New treatment alternatives to laser photocoagulation are on the horizon - the first of these, photodynamic therapy (PDT) with verteporfin, was approved by the US FDA in 2000. In this article we present a preliminary risk-benefit assessment of verteporfin in AMD, focusing on the landmark randomised, double-blind, placebo-controlled studies. The TAP (Treatment of Age-related macular degeneration with Photodynamic therapy) trial established the efficacy of PDT for classic subfoveal neovascularisation in AMD at 2 years follow-up. The VIP (Verteporfin in Photodynamic therapy) study concentrated on subfoveal occult-only lesions not included in the TAP study. After 2 years, treated eyes were less likely to experience visual loss. Exploratory analyses of TAP and VIP suggest that lesion size is a more significant predictor of the treatment benefit than either lesion composition or visual activity. The VIM (Visudyne in Minimally classic) trial altered the standard PDT light fluence rate in the treatment of subfoveal minimally classic lesions. This trial again demonstrated a beneficial effect for those receiving treatment with PDT. The VIO (Visudyne in Occult) trial, evaluating PDT in occult-only lesions as a confirmatory study of the VIP trial, did not achieve its primary end-point at 2 years. Further analyses are pending.PDT with verteporfin has an excellent safety profile that has been established with >1 million treatment applications. Cost-effectiveness data are limited but suggest that PDT may be a cost-effective treatment modality. Other FDA-approved treatments (pegaptanib, ranibizumab and bevacizumab) for neovascular AMD are discussed, as well as investigational substances such as anecortave acetate.

Saab G, Almony A, Blinder KJ, Schuessler R, Brennan DC. · No affiliation provided · Arch Ophthalmol. · Pubmed #18195237 No free full text.

This publication has no abstract.

Dhalla MS, Shah GK, Blinder KJ, Ryan EH, Mittra RA, Tewari A. · Barnes Retina Institute, St Louis, MO, USA. · Retina. · Pubmed #17151484 No free full text.

Abstract: PURPOSE: To examine the 7-month results for patients treated with combined photodynamic therapy (PDT) with verteporfin and intravitreal bevacizumab for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). METHODS: This is a retrospective series of 24 eyes with juxtafoveal or subfoveal CNV secondary to AMD. Patients were treated with PDT with verteporfin and 1.25 mg of intravitreal bevacizumab. All patients were naive to treatment and had either treatment within a 14-day interval. Main outcome measures were visual acuity stabilization (defined as no change or a gain in visual acuity) and retreatment rate. RESULTS: At the 7-month follow-up, 20 (83%) of 24 patients had stabilization of visual acuity. Sixteen eyes (67%) had improvement in visual acuity. Mean improvement in visual acuity (n = 24) was 2.04 Snellen lines. Fifteen eyes (63%) required only a single combined treatment for CNV resolution. There were no complications, including endophthalmitis, uveitis, and ocular hypertension. CONCLUSION: The results of this study suggest that combined treatment of PDT with verteporfin and intravitreal bevacizumab may be useful in treating neovascular AMD by reducing retreatment rates and improving visual acuity. Further investigation with large, controlled trials is warranted to outline the appropriate treatment paradigm for combination therapy.

Smith BT, Dhalla MS, Shah GK, Blinder KJ, Ryan EH, Mittra RA. · Barnes Retina Institute, St. Louis, Missouri, USA. · Retina. · Pubmed #18463509 No free full text.

Abstract: PURPOSE: To report the outcome for eyes treated with intravitreal injection of bevacizumab combined with verteporfin photodynamic therapy (PDT) for choroidal neovascularization (CNV) in age-related macular degeneration (AMD). STUDY DESIGN AND PARTICIPANTS: Interventional, consecutive, retrospective case series including 40 eyes of 40 patients with newly diagnosed juxtafoveal or subfoveal CNV secondary to AMD. METHODS: The charts of patients treated with a 1.25-mg intravitreal injection of bevacizumab followed by PDT within a 2-week period were reviewed. Main outcome measures were visual acuity stabilization (defined as no change or a gain in visual acuity) and need for retreatment. RESULTS: Thirty-three (83%) of 40 eyes had stabilization of visual acuity. Mean improvement in visual acuity was 1.73 lines. Twenty-six eyes (65%) required only a single intravitreal injection of bevacizumab combined with PDT. Of the 23 eyes with 12 months of follow-up, 17 (74%) had stabilization of visual acuity, while 9 (40%) had improvement in visual acuity (mean, 1.22 Snellen lines). Eleven eyes (48%) required only a single combined treatment for CNV resolution at the 12-month follow-up. Fifteen (88%) of 17 eyes with only 6 months of follow-up required only a single combined treatment. There were no complications such as endophthalmitis, uveitis, or ocular hypertension. CONCLUSION: These findings suggest that eyes treated with both intravitreal injection of bevacizumab and PDT require none to a minimal number of re-treatments to have stabilization of vision, even at 12 months of follow-up. Further investigation with large controlled trials is warranted to outline the appropriate treatment paradigm for combination therapy.

Dhalla MS, Fantin A, Blinder KJ, Bakal JA. · Barnes Retina Institute, St Louis, Missouri, USA. <> · Am J Ophthalmol. · Pubmed #17303062 No free full text.

Abstract: PURPOSE: To introduce a standardized macular photostress test using an automated perimeter as a method to quantify macular disease severity and as a tool to distinguish optic neuropathy from macular pathology. DESIGN: Prospective interventional pilot study. METHODS: Twenty-five bilaterally pseudophakic subjects aged range, 65 to 84: 15 patients with varying severity of non-neovascular age-related macular degeneration (AMD), five patients with no ocular disease, and five patients with moderate primary open-angle glaucoma (POAG). Previously reported normative values served as controls for this study. Patients underwent foveal threshold testing using the Humphrey Visual Field Perimeter Model 750 (Carl Zeiss Meditec, Inc, Dublin, California, USA). Baseline measurements were compared to threshold sensitivity after photostress at one minute and then two-minute intervals until sensitivity returned to baseline. Main outcome measures were baseline foveal threshold sensitivity, foveal threshold depression, and recovery following photostress. RESULTS: Automated macular photostress testing in macular disease (AMD) causes a decrease (P < .001) in baseline foveal sensitivity and a delay (P < .001) in recovery time to baseline sensitivity. Optic nerve pathology (POAG) does not affect (P = .343) the foveal response curve. CONCLUSIONS: The macular automated photostress (MAP) test is an inexpensive, noninvasive, and readily accessible adjunct for evaluating patients with macular disease. This standardized protocol is useful in objectively defining disease severity, may be used to follow response to treatment, and could aid in distinguishing optic neuropathy from macular pathology.

Dhalla MS, Blinder KJ, Tewari A, Hariprasad SM, Apte RS. · Barnes Retina Institute, St Louis, Missouri, USA. · Am J Ophthalmol. · Pubmed #16564819 No free full text.

Abstract: PURPOSE: To report two cases of a retinal pigment epithelial tear after intravitreal injection of pegaptanib sodium. To our knowledge, this is the first report of this finding after intraocular antivascular endothelial growth factor therapy. DESIGN: Observational case reports. METHODS: Two patients presented with occult choroidal neovascularization and associated serous pigment epithelial detachment that was a result of age-related macular degeneration. Both patients were treated with an intravitreal injection of pegaptanib sodium. RESULTS: One patient developed a retinal pigment epithelium tear one week after the intravitreal injection. The second patient developed a retinal pigment epithelium tear eight weeks after treatment. CONCLUSIONS: Although these cases may represent natural history, there should be a high index of suspicion for retinal pigment epithelium tears in patients who report significant visual deterioration after intravitreal injection of pegaptanib sodium. Further studies are needed to determine whether angiographic subtypes of choroidal neovascular membranes are more susceptible to developing retinal pigment epithelium tears after treatment with antivascular endothelial growth factor agents.

Hariprasad SM, Shah GK, Blinder KJ. · Department of Ophthalmology and Visual Science, University of Chicago, Chicago, Illinois, USA. · Am J Ophthalmol. · Pubmed #16387003 No free full text.

Abstract: PURPOSE: To report the changes and trends in intraocular pressures (IOP) following intravitreal injection of Pegaptanib (Macugen) for the treatment of exudative age-related macular degeneration. DESIGN: Retrospective chart review. METHODS: Review of 79 patients who underwent 122 consecutive Pegaptanib injections. Analysis of the short-term effect of Pegaptanib injections on IOP was performed. RESULTS: Baseline mean IOP was 15.73 +/- 3.41 mm Hg (mean +/- standard deviation) with a range of 9 to 27 mm Hg. Postinjection mean IOP was 24.47 +/- 6.29 mm Hg with a range of 8 to 36 mm Hg. Mean IOP change from baseline to roughly 30 minutes after Pegaptanib injection was 8.74 +/- 7.23 mm Hg. At the 5- to 7-day follow-up visit, IOP had normalized. CONCLUSIONS: Pegaptanib injection in this limited series seems to be safe from an IOP standpoint in the short-term. IOP monitoring postinjection may not be necessary.

Blinder KJ, Shah GK, Thomas MA, Holekamp NM, Joseph DP, Grand MG, Sharma S. · Barnes Retina Institute, Washington University School of Medicine, St Louis, Missouri, USA. · Ophthalmic Surg Lasers Imaging. · Pubmed #16238033 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: To describe the results of surgical treatment of peripapillary choroidal neovascularization in age-related macular degeneration as an option to both laser photocoagulation and photodynamic therapy. PATIENTS AND METHODS: Retrospective review of patients with peripapillary choroidal neovascularization secondary to age-related macular degeneration who were not eligible for or refused laser photocoagulation. Patients without the diagnosis of age-related macular degeneration and those who had extension of their neovascularization subfoveally were excluded from the review. RESULTS: Eleven patients total were identified who met the specified inclusion criteria. The male to female ratio was 4:7, with an age range of 63 to 94 years (mean = 78 years). The mean area of involved retina temporal to the optic disc was 5 clock hours, with the distance of the temporal edge of the lesion from the fovea ranging from 100 to 2,000 microm. The mean duration of follow-up was 23 months, with 27% (3 of 11) experiencing recurrent choroidal neovascularization. The preoperative and postoperative visual acuity ranges were both 20/25 to counting fingers. Sixty-four percent (7 of 11) of patients had stable or improved visual acuity postoperatively, with a mean visual acuity change of 1 line visual improvement. CONCLUSION: In cases where photodynamic therapy and laser photocoagulation are not indicated, the surgical treatment of peripapillary choroidal neovascularization secondary to age-related macular degeneration may prove beneficial.

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

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

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

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

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

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

Botelho PJ, Blinder KJ, Shahinfar S. · Department of Ophthalmology, Scott Air Force Base, Illinois 62225, USA. · Am J Ophthalmol. · Pubmed #10458190 No free full text.

Abstract: PURPOSE: To report the cotransmission of retinitis punctata albescens (RPA) and congenital sensorineural deafness. METHODS: Case reports of two siblings with nyctalopia and profound bilateral sensorineural deafness. RESULTS: The affected siblings, an 11-year-old female and a 7-year-old male, presented with decreased visual acuity and night blindness. In both eyes of both siblings, ophthalmoscopic evaluation disclosed numerous white spots at the level of the retinal pigment epithelium with macular sparing. The rod threshold dark adaptation and electroretinogram tracings were consistent with advanced rod-cone degeneration. CONCLUSION: Two affected members of a family were found to exhibit RPA and congenital sensorineural deafness. This pedigree supports the genetic cotransmission of the traits.