Jennifer I. Lim

Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study.

OBJECTIVES To determine the long-term effects of ranibizumab (RBZ) in patients with diabetic macular edema (DME). DESIGN Prospective, randomized, interventional, multicenter clinical trial. PARTICIPANTS One hundred twenty-six patients with DME. METHODS Subjects were randomized 1:1:1 to receive 0.5 mg RBZ at baseline and months 1, 3, and 5 (group 1), focal or grid laser photocoagulation at baseline and month 3 if needed (group 2), or a combination of 0.5 mg RBZ and focal or grid laser at baseline and month 3 (group 3). Starting at month 6, if retreatment criteria were met, all subjects could be treated with RBZ. MAIN OUTCOME MEASURES The mean change from baseline in best-corrected visual acuity (BCVA) at month 24. RESULTS After the primary end point at month 6, most patients in all groups were treated only with RBZ, and the mean number of injections was 5.3, 4.4, and 2.9 during the 18-month follow-up period in groups 1, 2, and 3, respectively. For the 33 patients in group 1, 34 patients in group 2, and 34 patients in group 3 who remained in the study through 24 months, the mean improvement in BCVA was 7.4, 0.5, and 3.8 letters at the 6-month primary end point, compared with 7.7, 5.1, and 6.8 letters at month 24, and the percentage of patients who gained 3 lines or more of BCVA was 21, 0, and 6 at month 6, compared with 24, 18, and 26 at month 24. The percentage of patients with 20/40 or better Snellen equivalent at month 24 was 45% in group 1, 44% in group 2, and 35% in group 3. Mean foveal thickness (FTH), defined as center subfield thickness, at month 24 was 340 μm, 286 μm, and 258 μm for groups 1, 2, and 3, respectively, and the percentage of patients with center subfield thickness of 250 μm or less was 36%, 47%, and 68%, respectively. CONCLUSIONS Intraocular injections of RBZ provided benefit for patients with DME for at least 2 years, and when combined with focal or grid laser treatments, the amount of residual edema was reduced, as were the frequency of injections needed to control edema. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia: 2-Year results of a randomized clinical trial - VIP report no. 3

PURPOSE To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia. DESIGN AND SETTING Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North America. PARTICIPANTS Patients with subfoveal choroidal neovascular lesions caused by pathologic myopia measuring no more than 5400 micro m and best-corrected visual acuity (approximate Snellen equivalent) of 20/100 or better. METHODS Similar to methods described for 1-year results with follow-up examinations beyond 1 year, continuing every 3 months (except Photograph Reading Center evaluations only at the month 24 examination). During the second year, the same regimen (with verteporfin or placebo as applied at baseline) was used if angiography showed fluorescein leakage from CNV. MAIN OUTCOME MEASURES The primary outcome was the proportion of eyes with fewer than 8 letters (approximately 1.5 lines) of visual acuity loss at the month 24 examination, adhering to an intent-to-treat analysis and using the last observation carried forward method to impute for any missing data. RESULTS Seventy-seven of 81 patients (95%) in the verteporfin group, compared with 36 of 39 patients (92%) in the placebo group, completed the month 24 examination. At this time point, 29 of 81 verteporfin-treated patients (36%) compared with 20 of 39 placebo-treated patients (51%) lost at least 8 letters (P = 0.11). The distribution of change in visual acuity at the month 24 examination was in favor of a benefit for the cases assigned to verteporfin (P = 0.05). This included improvement by at least 5 letters (equivalent to at least 1 line) in 32 verteporfin-treated cases [40%] vs. five placebo-treated cases (13%) and improvement by at least 15 letters (equivalent to at least 3 lines) in 10 verteporfin-treated cases (12%) vs. zero placebo-treated cases. No additional photosensitivity adverse reactions or injection site adverse events were associated with verteporfin therapy in the second year of follow-up. CONCLUSIONS Verteporfin therapy for subfoveal CNV caused by pathologic myopia safely maintained a visual benefit compared with a placebo therapy through 2 years of follow-up. Although the primary outcome was not statistically significantly in favor of verteporfin therapy at 2 years as it had been at 1 year of follow-up, the distribution of change in visual acuity at the month 24 examination was in favor of the verteporfin-treated group and showed that this group was more likely to have improved visual acuity through the month 24 examination. The VIP Study Group recommends verteporfin therapy for subfoveal CNV resulting from pathologic myopia based on both the 1- and 2-year results of this randomized clinical trial.

Primary End Point (Six Months) Results of the Ranibizumab for Edema of the mAcula in Diabetes (READ-2) Study

OBJECTIVES To compare ranibizumab with focal/grid laser or a combination of both in diabetic macular edema (DME). DESIGN Prospective, randomized, interventional, multicenter clinical trial. PARTICIPANTS A total of 126 patients with DME. METHODS Subjects were randomized 1:1:1 to receive 0.5 mg of ranibizumab at baseline and months 1, 3, and 5 (group 1, 42 patients), focal/grid laser photocoagulation at baseline and month 3 if needed (group 2, 42 patients), or a combination of 0.5 mg of ranibizumab and focal/grid laser at baseline and month 3 (group 3, 42 patients). MAIN OUTCOME MEASURES The primary end point was the change from baseline in best-corrected visual acuity (BCVA) at month 6. RESULTS At month 6, the mean gain in BCVA was significantly greater in group 1 (+7.24 letters, P = 0.01, analysis of variance) compared with group 2 (-0.43 letters), and group 3 (+3.80 letters) was not statistically different from groups 1 or 2. For patients with data available at 6 months, improvement of 3 lines or more occurred in 8 of 37 (22%) in group 1 compared with 0 of 38 (0%) in group 2 (P = 0.002, Fisher exact test) and 3 of 40 (8%) in group 3. Excess foveal thickness was reduced by 50%, 33%, and 45% in groups 1, 2, and 3, respectively. CONCLUSIONS During a span of 6 months, ranibizumab injections by the current protocol had a significantly better visual outcome than focal/grid laser treatment in patients with DME.

Indocyanine green angiography in chorioretinal diseases: indications and interpretation: An evidence-based update

UNLABELLED TOPIC/PURPOSE: To assess the clinical usefulness and relevance of indocyanine green angiography (ICG) in the investigation of chorioretinal disorders and assess specifically in what conditions it may add useful information to that obtained using standard fluorescein angiography. CLINICAL RELEVANCE Many publications on ICG have appeared in recent years touting its use in ophthalmology. These publications have led to increasing use of this technique and to its application in numerous retinal diseases in which the fluorescein angiographic findings have been thoroughly described. METHODS/LITERATURE REVIEWED During this systematic literature review, we identified and reviewed a total of 376 articles, from among which we selected 92 that we considered most relevant to our purpose of evaluating published evidence as to the efficacy of ICG. We excluded many articles with weak study designs and those that simply duplicated previously published information. Our literature search used PubMed and was confined to articles in English or that included an English abstract. RESULTS Our systematic review suggests that ICG has relatively few specific indications for use as justified by previously published peer-reviewed studies. In keeping with the requirements for this Journals evidence-based articles, we have divided our clinical recommendations for the use of ICG into three categories: (A) strongly recommended and supported by strong evidence; (B) recommended with moderately strong supporting evidence; (C) not recommended at present because supported only by anecdotal or group consensus evidence. We highly recommended ICG for (1) identification of polypoidal choroidal vasculopathy, (2) occult choroidal neovascularization, (3) neovascularization associated with pigment epithelial detachments, and (4) recurrent choroidal neovascular membranes. These are all conditions in which ICG contributes to the identification of lesions that may be treatable. We recommend ICG with some enthusiasm for identifying feeder vessels in age-related macular degeneration, choroidal neovascular membranes, chronic central serous retinopathy, multiple evanescent white dot syndrome, vasculitis, acute multifocal placoid pigment epitheliopathy, Vogt-Koyanagi-Harada syndrome, macular lesions associated with angioid streaks, and birdshot retinopathy. In all these conditions, ICG may help establish a diagnosis and provide some useful guidance for therapy. At present, we do not recommend ICG for scleritis and posterior scleritis, drusen differentiation, Behçets disease, or sarcoidosis, because it has not been demonstrated to add useful clinical information. CONCLUSIONS ICG, although now a well established technique, has clear advantage over fluorescein angiography in relatively few chorioretinal disorders. It has, however, contributed to the understanding of pathologic processes in many ocular diseases. As yet, no published randomized controlled clinical trials show any benefit to the use of ICG in the management of any specific ocular disease.

Characteristics of patients with cytomegalovirus retinitis in the era of highly active antiretroviral therapy

PURPOSE To describe the characteristics of patients with AIDS and cytomegalovirus retinitis in the era of highly active antiretroviral therapy (HAART). METHODS Prospective cohort study. Baseline (enrollment) data were compared between patients with newly diagnosed cytomegalovirus retinitis (incident cases) and those with previously diagnosed cytomegalovirus retinitis (prevalent cases). RESULTS As of December 31, 2000, 45 incident and 200 prevalent cases had been enrolled. Among prevalent cases, the median time from cytomegalovirus retinitis diagnosis was 2.9 years. Incident cases were more likely than prevalent cases to be women (35.4% vs 15.3%, P =.001), African American (45.4% vs 20.4%, P =.002), and uninsured (29.6% vs 7.6%, P <.001). Incident cases were less likely than prevalent cases to be on HAART (51.2% vs 77.6%, P =.001) and to have had an immunologic response to HAART (increase in CD4(+) T-cell count to > 100 cells/microl) (12.2% vs 57.5%, P <.001). The median CD4(+) T-cell count at enrollment among incident cases was 17 cells/microl and among prevalent cases was 159 cells/microl (P <.001). Immune recovery uveitis had been diagnosed in 15.5% of the prevalent cases. Sixty-three percent of prevalent cases were not on anticytomegalovirus therapy. CONCLUSIONS There is a population of patients with previously diagnosed and longstanding cytomegalovirus retinitis who have experienced immune recovery as a consequence of HAART and are no longer receiving anticytomegalovirus therapy. There are demographic differences between incident and prevalent cases that may reflect the evolution of the AIDS epidemic and differences in utilization of health care services.

MACULAR HOLE SURGERY USING THROMBIN-ACTIVATED FIBRINOGEN AND SELECTIVE REMOVAL OF THE INTERNAL LIMITING MEMBRANE

Purpose. To evaluate a tissue sealant (autologous cryoprecipitate activated with bovine thrombin) as an adjuvant in macular hole surgery. Methods. Sixty-nine patients with stage 2, 3, or 4 full-thickness macular hole were enrolled consecutively in a prospective pilot study. Anatomic closure of the macular holes with a single operation was the primary outcome. Fifty-eight patients had pre- and postoperative standardized measurements including best refracted visual acuity, reading speed, and contrast sensitivity. Group A patients (45) had primary macular holes; Group B patients (13) had recurrent macular holes or macular holes with “other” retinal pathology. Surgical technique was standardized and membrane dissections were optional. Results. The anatomic closure rate was 80% with a minimum of 6 months follow-up. Mean improvement in visual acuity for Group A (2.9 ± 0.4 lines) was significantly better than for Group B (0.8 ± 0.5 lines; P = 0.008). Eyes that underwent internal limiting membrane (ILM) dissections had an anatomic closure rate of 96% (23/24), compared with 71% (32/45) in “non-ILM” cases (P = 0.034). Adverse reactions included sterile hypopyon (10%), intraretinal hemorrhage (9%), pigmentary hyperplasia (3%), and retinal detachment (3%). Conclusion. Tissue sealants should be evaluated as an adjuvant in macular hole surgery in a randomized clinical trial. Inflammatory reactions may occur in some patients. Internal limiting membrane dissection may improve anatomic closure rates without adversely affecting the visual acuity.

Submacular surgery trials randomized pilot trial of laser photocoagulation versus surgery for recurrent choroidal neovascularization secondary to age-related macular degeneration: I. Ophthalmic outcomes. Submacular Surgery Trials Pilot Study report number 1

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.

Submacular Hemorrhage Removal

PURPOSE To determine whether pars plana vitrectomy combined with tissue plasminogen activator for evacuation of submacular hemorrhage results in improved visual acuity. METHODS Retrospective review of 18 patients who received a subretinal injection of tissue plasminogen activator during a pars plana vitrectomy to evacuate dense submacular hemorrhages. RESULTS Diagnoses included age-related macular degeneration (16 patients), ruptured macroaneurysm (1 patient), and penetrating ocular trauma (1 patient). Preoperative visual acuity ranged from 20/200 to counting fingers (median visual acuity, counting fingers). Follow-up ranged from 10 to 104 weeks (median, 33 weeks). Best postoperative visual acuity ranged from 20/30 to counting fingers (median, 20/300). Best postoperative visual acuity improved two or more lines in 11 (61%) of 18 eyes, remained unchanged in 4 (22%) of 18 eyes, and decreased two or more lines in 3 (17%) of 18 eyes (P = 0.10, Wilcoxon sign-rank test). Final visual acuity ranged from 20/40 to light perception (median, counting fingers). Final visual acuity improved two or more lines in 5 (28%) of 18 eyes, remained unchanged in 6 (33%) of 18 eyes, and decreased two or more lines in 7 (39%) of 18 eyes (P = 0.53, Wilcoxon sign-rank test). CONCLUSIONS Pars plana vitrectomy to evacuate massive subretinal hemorrhage can improve visual acuity, but final visual acuity is limited by the underlying disease.

Rapid response of retinal pigment epithelial detachments to intravitreal aflibercept in neovascular age-related macular degeneration refractory to bevacizumab and ranibizumab

PurposeThe aim of this study is to report the short-term efficacy of aflibercept in the treatment of neovascular age-related macular degeneration (AMD) with associated retinal pigment epithelial detachment (PED) which is refractory or develops tachyphylaxis to bevacizumab and ranibizumab.MethodsThe method comprised a retrospective review of the medical records of patients with neovascular AMD and associated PEDs recently treated with aflibercept and previously treated with bevacizumab and ranibizumab.ResultsThree eyes of three female patients of ages 49, 55, and 65 years old with large serous PEDs and subretinal fluid (SRF) associated with occult choroidal neovascularization and neovascular AMD were treated with aflibercept after intravitreal bevacizumab and/or ranibizumab failed to resolve the lesions. All had complete resolution of SRF and complete or near-complete resolution of the PEDs after aflibercept injections over a 3-month period. Visual acuity improved in all three eyes.ConclusionIntravitreal aflibercept may be an effective treatment option for serous PED in neovascular AMD patients after bevacizumab and ranibizumab have previously failed. Larger studies with longer follow-up are required to determine the role of aflibercept in treatment of PED in neovascular AMD.

A Pilot Study of Fourier-Domain Optical Coherence Tomography of Retinal Dystrophy Patients

PURPOSE To characterize the macular anatomy of retinal dystrophy eyes using high-speed, high-resolution, Fourier-domain optical coherence tomography (FD-OCT). DESIGN Case-control study. METHODS Retinal dystrophy patients and normal age- and gender-matched controls underwent FD-OCT imaging using the RTVue (Optovue Inc., Fremont, California, USA). Vertical and horizontal 8-mm scans of 1024 lines/cross-section were obtained. Based on boundaries manually drawn on computer displays of OCT cross-sections, the thicknesses of the retina, inner retinal layer (IRL), and outer retinal layer (ORL) were averaged over both 5-mm (macular) and 1.5-mm (foveal) regions centered at the fovea. The IRL was the sum of nerve fiber layer (NFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) thicknesses. Total retinal thickness (RT) was measured between the internal limiting membrane (ILM) and the retinal pigment epithelium. ORL thickness was calculated by subtracting IRL thickness from RT. RESULTS Fourteen patients (three retinitis pigmentosa, two cone-rod degeneration, two Stargardt disease, and seven normal controls) underwent FD-OCT imaging. Mean foveal RT was 271.3 +/- 23.3 microm for controls and 158.4 +/- 47.1 microm for retinal dystrophy patients (P < .001). Mean macular RT was 292.8 +/- 8.1 microm for controls and 199.1 +/- 32.6 microm for retinal dystrophy patients (P < .001). Mean macular ORL was 182.9 +/- 4.7 microm for controls and 101.3 +/- 18.7 microm for retinal dystrophy patients (P < .001); mean macular IRL was 109.9 +/- 6.4 microm for controls and 97.9 +/- 20.7 microm for retinal dystrophy patients (P = .06). CONCLUSION Eyes with retinal dystrophy had a small (11%) decrease in macular IRL and severe (45%) decrease in macular ORL compared to normal controls.