Highlights of the 41st Annual Meeting of the Retina Society
Highlights of the 41st Annual Meeting of the Retina Society
Introduction
The Retina Society gathered for its annual meeting in Scottsdale, Arizona, September 25-28, 2008. Presentations from members of the society included updates on basic science as well as translational and clinical research. Named lectures were given and, as usual, were some of the high points of the meeting. This review highlights some of the most promising findings in medical therapy and surgical approaches to retinal disease as presented at the meeting.
Medical Therapy Approaches to Retinal Disease
Dante Pieramici, MD, presented results of a small trial evaluating the use of the vascular endothelial growth factor (VEGF) inhibitor ranibizumab in the management of central retinal vein occlusions (CRVO). The 20-patient trial compared outcomes of those receiving monthly vs quarterly injections of ranibizumab. Cohort 1 (n = 10) received 3 monthly ranibizumab injections and then quarterly doses as needed, and cohort 2 (n = 10) received 3 monthly injections and then monthly doses as needed. Patients in cohort 2 (the monthly dosing) appeared to have a better outcome, at least in the short term: At the 6-month timepoint, patients in cohort 1 had a mean improvement in visual acuity of 2.5 letters, compared with a mean improvement in visual acuity of 6.9 letters in cohort 2. Further study of ranibizumab in CRVO is under way, including a phase 3 multicenter clinical trial.
David Brown, MD, reviewed the 52-week results of a phase 2 interval-ranging study of intravitreal VEGF Trap-Eye (a fully human and soluble VEGF receptor fusion protein that binds all forms of VEGF-A as well as related placental growth factor) in patients with wet age-related macular degeneration (AMD). A total of 159 patients enrolled in 5 groups in the study; 134 (84.3%) completed 52 weeks of follow-up. Two groups (0.5 mg and 2 mg) received VEGF Trap-Eye at 4-week intervals over the first 12 weeks and then as needed until 52 weeks. Three groups (0.5 mg, 2 mg, and 4 mg) received VEGF Trap-Eye at a 12-week interval over the first 12 weeks and then as needed until 52 weeks. During the as-needed dosing phase from weeks 12 to 52, all patients grouped together received a mean number of 2.01 injections with VEGF Trap-Eye. The mean gain in visual acuity among all patients was 5.3 letters at 52 weeks. Notably, the patients who received a loading dose of VEGF Trap-Eye (those patients receiving a dose every 4 weeks during the initial 12 weeks of the study) seemed to have an improved outcome. In particular, patients receiving the 2-mg dose every 4 weeks during the first 12 weeks and then as needed during weeks 12 through 52 had better visual acuity results (mean gain of 9 letters). The implication is that a loading or induction phase of treatment may be an important strategy for obtaining the best possible visual acuity results when treating exudative AMD with an intravitreal anti-VEGF agent. Serious adverse events were rare. One patient had culture-negative endophthalmitis, and there were 2 deaths (1 from preexisting pulmonary hypertension and 1 from pancreatic cancer) and 1 arterial thromboembolic event (a stroke in a patient with a history of stroke). VEGF Trap-Eye is currently being evaluated in the treatment of wet AMD in a large, multicenter phase 3 trial comparing it head-to-head against ranibizumab.
Victor Gonzalez, MD, presented the results of the MIVI III trial, a phase 2 trial evaluating several doses of intravitreous microplasmin, an active component of the enzyme plasmin that has been shown to facilitate induction of a posterior vitreous detachment (PVD). In the study, patients without a prior PVD were enrolled before a planned pars plana vitrectomy. The most common diagnoses in enrolled patients included vitreomacular traction and macular hole. Patients received either a placebo injection of saline fluid or an injection of 1 of 3 doses of microplasmin (25, 75, or 125 μg) 1 week prior to planned pars plana vitrectomy. At 1 week after injection, 20 of 94 (21%) patients receiving microplasmin (including 10 of 32 [31%] of the patients receiving the 125 μg dose) had a total PVD. Of the patients receiving a placebo injection, 3/31(9.6%) patients had a total PVD. At the 1-week timepoint, pars plana vitrectomy surgery was planned. Of note, 18 of 94 (19%) patients receiving microplasmin did not require surgery. Furthermore, 10 of 32 (31%) patients receiving the highest dose of microplasmin (125 μg) did not require surgery, either due to release of vitreomacular traction or closure of a macular hole. At the 35-day timepoint, patients receiving microplasmin had, on average, a 4.7-letter improvement in visual acuity. Patients receiving the 125-μg dose had, on average, a 6.9-letter improvement in visual acuity. There were no significant safety signals noted, such as increased risk for retinal tear or detachment. Dr. Gonzalez highlighted the exciting possibility of treating surgical conditions, such as vitreomacular traction and macular hole, with an outpatient office-based intravitreal injection. An upcoming phase 3 clinical trial will further evaluate the safety and efficacy of intravitreal microplasmin in the treatment of vitreomacular traction and macular hole.
Surgical Approaches to Retinal Disease
Alan Ruby, MD, reviewed long-term rates of retinal detachment following 25-gauge vitrectomy surgery. The retrospective review looked at 179 eyes that underwent 25-gauge transconjunctival sutureless vitrectomy and excluded cases initially presenting with a retinal detachment or tear. Mean follow-up was 560 days. The overall rate of retinal detachment after 25-gauge vitrectomy was 2.79% (5 of 179). In the phakic group (48% of eyes), 4 of 86 (4.65%) had a retinal detachment. In the pseudophakic group (51% of eyes), 1 of 91 (1.1%) had a retinal detachment. The authors speculated that the increased rate of retinal detachment in the phakic cases may be related to a less complete vitrectomy. However, they also noted that the rate of retinal detachment after 25-gauge vitrectomy was relatively low and comparable to previously reported rates for 20-gauge vitrectomy.
H. Richard McDonald, MD, reported on complications that may arise in vitreoretinal procedures as a result of poorly secured clear corneal wounds. He described 5 cases of vitrectomy that were complicated by choroidal detachments, including 4 hemorrhagic choroidal detachments, that resulted from an inadequately closed clear corneal wound. He strongly recommended securing any clear corneal wound prior to initiating any vitreoretinal procedure.
Mehran Taban, MD, delivered a talk on a study of small-gauge sutureless vitrectomy wounds in cadaver eyes. Both 23- and 25-gauge wounds were evaluated. Straight wounds were compared with angled wounds using India ink and optical coherence tomography (OCT) under simulated conditions of intermittent elevations in intraocular pressure. In all cases, angled wounds showed better wound apposition and less leakage of India ink. With very real concerns in regard to the risks for hypotony and endophthalmitis after small-gauge vitrectomy surgery, Dr. Taban recommended angled entry wounds for both 23- and 25-gauge transconjunctival sutureless vitrectomy surgery and advised suturing all straight 23-gauge transconjunctival entry wounds.
Edward Hall, MD, reported on cytokine profiles of an experimental model of infectious endophthalmitis. Either Staphylococcus epidermidis or Bacillus cereus was injected into 1 eye of 69 rabbits. The other eye served as a control. Most injected eyes developed signs of endophthalmitis within 24 hours of inoculation. The infected eyes were then left untreated or were treated with either intravitreal vancomycin alone or intravitreal vancomycin and dexamethasone. They were followed for clinical signs of inflammation and then evaluated for intravitreal cytokine levels (including interleukin-1, interleukin-2, and interleukin-8) after euthanasia. Of note, cytokine levels found in the vitreous contents correlated very well with clinical signs of inflammation. Cytokine levels in treated animals were significantly lower than in untreated animals. The authors theorized that a greater understanding of the specific inflammatory modulators involved in endophthalmitis may lead to improved diagnostic and therapeutic options for patients.
Less Common Retinal Diseases
Larry Yannuzzi, MD, presented an engaging talk for the J. Donald M. Gass lecture on macular telangiectasia type II, also known as idiopathic perifoveal telangiectasia. Dr. Yannuzzi reviewed some new insights into the disease that have been reached recently on the basis of enhanced imaging capabilities, such as the use of OCT. Fluorescein angiographic findings were also reviewed. Although these patients have late hyperfluorescence on fluorescein angiography, they only rarely have macular edema. Visual symptoms are often linked to progressive atrophy of the fovea, which has become increasingly evident on the basis of OCT imaging. Examinations of these patients often show progressive atrophy of the perifoveal region, evidenced as cystic spaces on OCT.
William Tasman, MD, received the Retina Research Award of Merit and delivered the Charles Schepens lecture covering familial exudative vitreoretinopathy (FEVR). Dr. Tasman reviewed the history of the disease, prior presentations (including one given at the first meeting of the Retina Society), and particular diagnostic and therapeutic challenges of FEVR. In particular, screening of family members may unmask other cases; management may include observation, laser, or, in some instances, surgery. Surgical treatment of retinal detachments in FEVR may be challenging due to the tractional component of the disease.
Introduction
The Retina Society gathered for its annual meeting in Scottsdale, Arizona, September 25-28, 2008. Presentations from members of the society included updates on basic science as well as translational and clinical research. Named lectures were given and, as usual, were some of the high points of the meeting. This review highlights some of the most promising findings in medical therapy and surgical approaches to retinal disease as presented at the meeting.
Medical Therapy Approaches to Retinal Disease
Dante Pieramici, MD, presented results of a small trial evaluating the use of the vascular endothelial growth factor (VEGF) inhibitor ranibizumab in the management of central retinal vein occlusions (CRVO). The 20-patient trial compared outcomes of those receiving monthly vs quarterly injections of ranibizumab. Cohort 1 (n = 10) received 3 monthly ranibizumab injections and then quarterly doses as needed, and cohort 2 (n = 10) received 3 monthly injections and then monthly doses as needed. Patients in cohort 2 (the monthly dosing) appeared to have a better outcome, at least in the short term: At the 6-month timepoint, patients in cohort 1 had a mean improvement in visual acuity of 2.5 letters, compared with a mean improvement in visual acuity of 6.9 letters in cohort 2. Further study of ranibizumab in CRVO is under way, including a phase 3 multicenter clinical trial.
David Brown, MD, reviewed the 52-week results of a phase 2 interval-ranging study of intravitreal VEGF Trap-Eye (a fully human and soluble VEGF receptor fusion protein that binds all forms of VEGF-A as well as related placental growth factor) in patients with wet age-related macular degeneration (AMD). A total of 159 patients enrolled in 5 groups in the study; 134 (84.3%) completed 52 weeks of follow-up. Two groups (0.5 mg and 2 mg) received VEGF Trap-Eye at 4-week intervals over the first 12 weeks and then as needed until 52 weeks. Three groups (0.5 mg, 2 mg, and 4 mg) received VEGF Trap-Eye at a 12-week interval over the first 12 weeks and then as needed until 52 weeks. During the as-needed dosing phase from weeks 12 to 52, all patients grouped together received a mean number of 2.01 injections with VEGF Trap-Eye. The mean gain in visual acuity among all patients was 5.3 letters at 52 weeks. Notably, the patients who received a loading dose of VEGF Trap-Eye (those patients receiving a dose every 4 weeks during the initial 12 weeks of the study) seemed to have an improved outcome. In particular, patients receiving the 2-mg dose every 4 weeks during the first 12 weeks and then as needed during weeks 12 through 52 had better visual acuity results (mean gain of 9 letters). The implication is that a loading or induction phase of treatment may be an important strategy for obtaining the best possible visual acuity results when treating exudative AMD with an intravitreal anti-VEGF agent. Serious adverse events were rare. One patient had culture-negative endophthalmitis, and there were 2 deaths (1 from preexisting pulmonary hypertension and 1 from pancreatic cancer) and 1 arterial thromboembolic event (a stroke in a patient with a history of stroke). VEGF Trap-Eye is currently being evaluated in the treatment of wet AMD in a large, multicenter phase 3 trial comparing it head-to-head against ranibizumab.
Victor Gonzalez, MD, presented the results of the MIVI III trial, a phase 2 trial evaluating several doses of intravitreous microplasmin, an active component of the enzyme plasmin that has been shown to facilitate induction of a posterior vitreous detachment (PVD). In the study, patients without a prior PVD were enrolled before a planned pars plana vitrectomy. The most common diagnoses in enrolled patients included vitreomacular traction and macular hole. Patients received either a placebo injection of saline fluid or an injection of 1 of 3 doses of microplasmin (25, 75, or 125 μg) 1 week prior to planned pars plana vitrectomy. At 1 week after injection, 20 of 94 (21%) patients receiving microplasmin (including 10 of 32 [31%] of the patients receiving the 125 μg dose) had a total PVD. Of the patients receiving a placebo injection, 3/31(9.6%) patients had a total PVD. At the 1-week timepoint, pars plana vitrectomy surgery was planned. Of note, 18 of 94 (19%) patients receiving microplasmin did not require surgery. Furthermore, 10 of 32 (31%) patients receiving the highest dose of microplasmin (125 μg) did not require surgery, either due to release of vitreomacular traction or closure of a macular hole. At the 35-day timepoint, patients receiving microplasmin had, on average, a 4.7-letter improvement in visual acuity. Patients receiving the 125-μg dose had, on average, a 6.9-letter improvement in visual acuity. There were no significant safety signals noted, such as increased risk for retinal tear or detachment. Dr. Gonzalez highlighted the exciting possibility of treating surgical conditions, such as vitreomacular traction and macular hole, with an outpatient office-based intravitreal injection. An upcoming phase 3 clinical trial will further evaluate the safety and efficacy of intravitreal microplasmin in the treatment of vitreomacular traction and macular hole.
Surgical Approaches to Retinal Disease
Alan Ruby, MD, reviewed long-term rates of retinal detachment following 25-gauge vitrectomy surgery. The retrospective review looked at 179 eyes that underwent 25-gauge transconjunctival sutureless vitrectomy and excluded cases initially presenting with a retinal detachment or tear. Mean follow-up was 560 days. The overall rate of retinal detachment after 25-gauge vitrectomy was 2.79% (5 of 179). In the phakic group (48% of eyes), 4 of 86 (4.65%) had a retinal detachment. In the pseudophakic group (51% of eyes), 1 of 91 (1.1%) had a retinal detachment. The authors speculated that the increased rate of retinal detachment in the phakic cases may be related to a less complete vitrectomy. However, they also noted that the rate of retinal detachment after 25-gauge vitrectomy was relatively low and comparable to previously reported rates for 20-gauge vitrectomy.
H. Richard McDonald, MD, reported on complications that may arise in vitreoretinal procedures as a result of poorly secured clear corneal wounds. He described 5 cases of vitrectomy that were complicated by choroidal detachments, including 4 hemorrhagic choroidal detachments, that resulted from an inadequately closed clear corneal wound. He strongly recommended securing any clear corneal wound prior to initiating any vitreoretinal procedure.
Mehran Taban, MD, delivered a talk on a study of small-gauge sutureless vitrectomy wounds in cadaver eyes. Both 23- and 25-gauge wounds were evaluated. Straight wounds were compared with angled wounds using India ink and optical coherence tomography (OCT) under simulated conditions of intermittent elevations in intraocular pressure. In all cases, angled wounds showed better wound apposition and less leakage of India ink. With very real concerns in regard to the risks for hypotony and endophthalmitis after small-gauge vitrectomy surgery, Dr. Taban recommended angled entry wounds for both 23- and 25-gauge transconjunctival sutureless vitrectomy surgery and advised suturing all straight 23-gauge transconjunctival entry wounds.
Edward Hall, MD, reported on cytokine profiles of an experimental model of infectious endophthalmitis. Either Staphylococcus epidermidis or Bacillus cereus was injected into 1 eye of 69 rabbits. The other eye served as a control. Most injected eyes developed signs of endophthalmitis within 24 hours of inoculation. The infected eyes were then left untreated or were treated with either intravitreal vancomycin alone or intravitreal vancomycin and dexamethasone. They were followed for clinical signs of inflammation and then evaluated for intravitreal cytokine levels (including interleukin-1, interleukin-2, and interleukin-8) after euthanasia. Of note, cytokine levels found in the vitreous contents correlated very well with clinical signs of inflammation. Cytokine levels in treated animals were significantly lower than in untreated animals. The authors theorized that a greater understanding of the specific inflammatory modulators involved in endophthalmitis may lead to improved diagnostic and therapeutic options for patients.
Less Common Retinal Diseases
Larry Yannuzzi, MD, presented an engaging talk for the J. Donald M. Gass lecture on macular telangiectasia type II, also known as idiopathic perifoveal telangiectasia. Dr. Yannuzzi reviewed some new insights into the disease that have been reached recently on the basis of enhanced imaging capabilities, such as the use of OCT. Fluorescein angiographic findings were also reviewed. Although these patients have late hyperfluorescence on fluorescein angiography, they only rarely have macular edema. Visual symptoms are often linked to progressive atrophy of the fovea, which has become increasingly evident on the basis of OCT imaging. Examinations of these patients often show progressive atrophy of the perifoveal region, evidenced as cystic spaces on OCT.
William Tasman, MD, received the Retina Research Award of Merit and delivered the Charles Schepens lecture covering familial exudative vitreoretinopathy (FEVR). Dr. Tasman reviewed the history of the disease, prior presentations (including one given at the first meeting of the Retina Society), and particular diagnostic and therapeutic challenges of FEVR. In particular, screening of family members may unmask other cases; management may include observation, laser, or, in some instances, surgery. Surgical treatment of retinal detachments in FEVR may be challenging due to the tractional component of the disease.
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