Matteo G. Cereda

Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration

Background/aims Real-life anti-vascular endothelial growth factor (VEGF) therapy use in patients with wet age-related macular degeneration (wAMD) was assessed in a retrospective, observational study in Canada, France, Germany, Ireland, Italy, the Netherlands, UK and Venezuela. Methods Medical records of patients with wAMD, who started ranibizumab treatment between 1 January 2009 and 31 August 2009, were evaluated. Data were collected until the end of treatment and/or monitoring or until 31 August 2011. Results 2227 patients who received ≥1 anti-VEGF injection with a baseline visual acuity assessment and ≥1 postbaseline visual acuity assessment for the treated eye were evaluated. Visual acuity improved until about day 120; thereafter, visual acuity gains were not maintained. Mean change in visual acuity score from baseline to years 1 and 2 was +2.4 and +0.6 letters, respectively. Patients received a mean of 5.0 and 2.2 injections in the first and second year, respectively. There were substantial differences in visual outcomes and injection frequency between countries. More frequent visits and injections were associated with greater improvements in visual acuity. Conclusions In clinical practice, fewer injections are administered than in clinical trials. Anti-VEGF treatment resulted in an initial improvement in visual acuity; however, this was not maintained over time. Trial registration number NCT01447043.

Postoperative complications and intraocular pressure in 943 consecutive cases of 23-gauge transconjunctival pars plana vitrectomy with 1-year follow-up.

Background: To report the rate of postoperative complications in 943 consecutive eyes operated on with 23-gauge transconjunctival pars plana vitrectomy. Methods: Single-center, retrospective, noncomparative, interventional case series. Nine hundred and forty-three eyes underwent 23-gauge transconjunctival core and peripheral vitrectomy with peripheral laser at the sclerotomy sites from May 2005 through April 2008. The main outcome measures were intraocular pressure at 1 day and at 1 week and intra- and postoperative complications with at least 6-month follow-up. Results: Eight hundred and thirty-one eyes (88%) did not have either significant intra- or postoperative complications. Sclerotomy leakage requiring suture occurred in 37 eyes (3.9%). One choroidal detachment (0.1%) spontaneously resolved 1 week after surgery. At postoperative Day 1, 31 eyes (3.3%) experienced transient hypotony. Forty-five eyes (4.8%) presented a subtle vitreous hemorrhage that resolved spontaneously. Two retinal detachments (0.2%) occurred, one at 1 month and one at 3 months. They resolved with one further vitrectomy. Seven hundred and forty eyes completed the 12-month follow-up and presented no further complications. Conclusion: Twenty-three–gauge complete vitrectomy and peripheral laser seem safe for a variety of vitreoretinal surgical procedures. The rate of post- and intraoperative complications compares favorably with 25-gauge and with the standard 20-gauge vitrectomy.

Artifacts in automatic retinal segmentation using different optical coherence tomography instruments.

Purpose: The purpose of this study was to compare and evaluate artifact errors in automatic inner and outer retinal boundary detection produced by different time-domain and spectral-domain optical coherence tomography (OCT) instruments. Methods: Normal and pathologic eyes were imaged by six different OCT devices. For each instrument, standard analysis protocols were used for macular thickness evaluation. Error frequencies, defined as the percentage of examinations affected by at least one error in retinal segmentation (EF-exam) and the percentage of total errors per total B-scans, were assessed for each instrument. In addition, inner versus outer retinal boundary delimitation and central (1,000 &mgr;m) versus noncentral location of errors were studied. Results: The study population of the EF-exam for all instruments was 25.8%. The EF-exam of normal eyes was 6.9%, whereas in all pathologic eyes, it was 32.7% (P < 0.0001). The EF-exam was highest in eyes with macular holes, 83.3%, followed by epiretinal membrane with cystoid macular edema, 66.6%, and neovascular age-related macular degeneration, 50.3%. The different OCT instruments produced different EF-exam values (P < 0.0001). The Zeiss Stratus produced the highest percentage of total errors per total B-scans compared with the other OCT systems, and this was statistically significant for all devices (P ≤ 0.005) except the Optovue RTvue-100 (P = 0.165). Conclusion: Spectral-domain OCT instruments reduce, but do not eliminate, errors in retinal segmentation. Moreover, accurate segmentation is lower in pathologic eyes compared with normal eyes for all instruments. The important differences in EF among the instruments studied are probably attributable to analysis algorithms used to set retinal inner and outer boundaries. Manual adjustments of retinal segmentations could reduce errors, but it will be important to evaluate interoperator variability.

Key drivers of visual acuity gains in neovascular age-related macular degeneration in real life: findings from the AURA study

Background/aims To identify predictive markers for the outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD). Methods AURA was a retrospective, observational, multicentre study that monitored the 2-year outcomes following intravitreal ranibizumab treatment in patients with nAMD. Using stepwise regression analysis, we evaluated the association between visual acuity outcomes, baseline characteristics and resource utilisation in order to determine which variables are significantly linked to outcomes in AURA. We also examined the relationship between visual acuity outcomes and number of injections received. Results Analyses were performed using data from year 1 (n=1695) and year 2 completers (n=1184). Logistic analysis showed that baseline visual acuity score, age at start of therapy, number of ophthalmoscopies and optical coherence tomography (OCT) (combined) and number of injections (ranibizumab) were significant (p<0.05) prognostic factors for vision maintenance (loss <15 letters) or vision gain (≥15 letters). Patients who received >7 injections (in 1 year) or >14 injections (over 2 years) gained more letters and demonstrated greater vision maintenance (loss of <15 letters) than patients who received fewer injections. There was a significant (p<0.05) association between number of injections and national reimbursement schemes and OCT. Conclusions A number of factors that are predictive of treatment outcomes in a real-life setting were identified. Notably, the decline of treatment benefits may be linked to number of injections and a failure to visit clinicians and receive OCT as required. These findings may be helpful in guiding ophthalmologist treatment decisions under limited time and financial constraints. Trial registration number NCT01447043.

Pearls and pitfalls in diagnosis and management of coats disease

Purpose: To review current literature on Coats disease and provide a structured framework for differentiating challenging clinical features in Coats disease patients. Methods: We critically reappraise historical and current literature and present clinical methods for developing a thorough differential diagnosis and management strategy for Coats disease. Results: Coats disease is a sporadic, usually unilateral condition typically occurring in young males. When untreated, this disorder can lead to total exudative retinal detachment and secondary glaucoma. Conclusions: Anti-VEGF agents are currently a treatment option in combination with ablative therapy of telangiectatic vessels. Anti-VEGF agents appear particularly useful for patients with extensive areas of exudative retinal detachment, and are an effective treatment option for total retinal detachment.

Macular translocation with 360° retinotomy for management of retinal pigment epithelial tear: long-term results

Background To determine long-term functional and morphological changes after full macular translocation (FMT) with 360° retinotomy in patients with retinal pigment epithelium (RPE) tears, in light of the increasing number of reports of this complication following vascular endothelial growth factor (VEGF)-modulating therapy. Methods We retrospectively reviewed a consecutive series of six patients with RPE tears secondary to neovascular age-related macular degeneration who underwent FMT with 360° retinotomy between March 2005 and June 2006. Preoperative and postoperative visual acuity, fundus fluorescein angiography (FA) and optical coherence tomography (OCT) were reviewed. RPE tears occurred spontaneously in three cases and after intravitreal triamcinolone in three cases. Preoperative and postoperative best-corrected visual acuity was converted to logarithm of the minimal angle of resolution visual acuity for analysis. Results Mean postoperative follow-up was 39 months (range 36–50 months). At 12, 24 and 36 months mean visual acuity increased by 6.00 (5.3), 5.57 (5.54) and 6.67 (4.76) lines, respectively. This improvement was maintained at final examination. FA and OCT revealed pigment epithelium atrophy extending to the new fovea in one case only, which also had longer symptom duration. Conclusions Long-term follow-up of FMT showed significant improvement in the majority of patients. FMT may be an option for cases of RPE tears of recent onset. Further investigations are necessary to determine FMTs role in tears developing during the course of anti-VEGF therapy.

INTRAVITREAL VERSUS SUBRETINAL ADMINISTRATION OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR COMBINED WITH GAS FOR ACUTE SUBMACULAR HEMORRHAGES DUE TO AGE-RELATED MACULAR DEGENERATION: An Exploratory Prospective Study.

Purpose: Current management of submacular hemorrhage (SMH) favors vitrectomy and gas with subretinal administration of recombinant tissue plasminogen activator (rtPA) over mere intravitreal rtPA injections and gas. In this study, we aimed to compare the effectiveness of both treatment modalities to displace submacular blood. Methods: Twenty-four patients with SMH secondary to age-related macular degeneration were included. The SMH had to exist ⩽14 days at time of surgery and SMH thickness had to be between 250 &mgr;m and 1,250 &mgr;m. Patients were randomized to either intravitreal injections of rtPA, perfluoropropane (C3F8) gas, and bevacizumab (n = 12) or vitrectomy with subretinal rtPA administration, intravitreal C3F8 gas, and bevacizumab (n = 12). The SMH volume change was measured on spectral domain optical coherence tomography postoperatively within a 2.5-mm cylinder centered at the fovea. Results: Median relative volume reduction of subretinal blood at 6 weeks postoperatively was 97% (95% confidence interval: 91–99%) in the intravitreal rtPA group and 100% (95–100%) in the subretinal rtPA group and did not differ significantly between groups (P = 0.56). Conclusion: Both treatment modalities effectively displaced SMH in this exploratory clinical trial. To more definitely study the noninferiority of intravitreal rtPA with gas to subretinal rtPA, vitrectomy with gas, a larger clinical trial would be necessary.

Early Perfusion of a Free RPE–Choroid Graft in Patients with Exudative Macular Degeneration Can Be Imaged with Spectral Domain–OCT

PURPOSE To study early flow and revascularization in a free, autologous, retinal pigment epithelium (RPE)-choroid graft. METHODS This prospective cohort study used spectral domain-optical coherence tomography (SD-OCT) after RPE-choroid graft surgery in 12 patients. This SD-OCT was combined with fluorescein angiography (FA) and indocyanine green angiography (ICGA) in 5 patients. RESULTS SD-OCT revealed that vessel diameter, number of vessels, and graft thickness increased in 10 of 12 patients, starting between 3 and 10 days after surgery. A subsequent decrease in thickness was found in all 10 patients, beginning as early as 8 days after surgery. Initially, the graft vessels were optically clearer than the underlying choroidal recipient vessels. Between 8 and 30 days after surgery, the optically clear vessels became gray, similar to the recipient choroid. FA and ICGA revealed perfusion in 4 of 5 patients between postoperative days 6 and 15. Between postoperative days 12 and 60, the entire choroidal structure of the graft was visible on ICGA. CONCLUSIONS; These data suggest that enlargement of vessel diameter, increase in the number of choroidal vessels, and graft thickening visualized by SD-OCT correspond with the ingrowth of afferent vessels, as demonstrated by ICGA. The subsequent establishment of efferent vessels results in flow, imaged as a change in color of the grafts vessels from optically clear to gray, graft thinning on SD-OCT, and complete revascularization on ICGA. SD-OCT, a noninvasive examination, can be used to demonstrate early graft perfusion in patients (trialregister.nl/trialreg/admin/rctview.asp number, NTR1768).

Determinants of visual acuity outcomes in eyes with neovascular AMD treated with anti-VEGF agents: an instrumental variable analysis of the AURA study.

PurposeTo identify the strongest variable(s) linked with the number of ranibizumab injections and outcomes in AURA, and to identify ways to improve outcomes using this association.MethodsAURA was a large observational study that monitored visual acuity over a 2-year period in patients with neovascular age-related macular degeneration (AMD) who received ranibizumab injections. Baseline characteristics, resource use, and outcomes were analyzed using an instrumental variable approach and regression analysis.ResultsData were analyzed from 2227 patients enrolled in AURA. Optical coherence tomography (OCT) and ophthalmoscopy were the most common diagnostic tests used, and this combination was the strongest instrumental variable. Use of OCT and ophthalmoscopy affected the number of injections given and resulted in an increase in visual acuity gains from baseline of 17.6 letters in year 1 and 2.5 letters in year 2. Regression models using the instrumental variable (OCT and ophthalmoscopy combined) showed that ≥5.1 (95% CI: 3.3–11.4) ranibizumab injections were needed to maintain visual acuity from baseline to year 1 and ≥8.3 (95% CI: 5.3–18.8) injections were needed to maintain visual acuity from year 1 to year 2. To gain ≥15 letters, ≥7.9 (95% CI: 5.1–17.5) ranibizumab injections would be needed in year 1 and ≥16.1 (95% CI: 10.3–36.4) injections would be needed over 2 years.ConclusionsThese findings highlight the role that regular monitoring plays in guiding neovascular AMD therapy and they showed that the number of ranibizumab injections needed to maintain visual acuity is higher than that administered in AURA.

Macular Hypotrophy After Internal Limiting Membrane Removal For Diabetic Macular Edema

Purpose: To compare the anatomic and functional effects of three different approaches to nontractional diabetic macular edema. Methods: Retrospective comparative study. Sixty eyes of 60 patients diagnosed with cystoid diabetic macular edema and treated with 1.25 mg/mL intravitreal bevacizumab (Group A), laser photocoagulation (Group B), or vitrectomy with inner limiting membrane peeling (Group C) were included in the study. Changes in number of Early Treatment Diabetic Retinopathy Study letters, central macular thickness, largest diameter of the intraretinal cysts (IC), and choroidal thickness were investigated. Analyses were performed during follow-up visits at Months 1, 3, 6, 9, and 12. Results: Visual acuity only significantly improved in Group A at the last follow-up (P = 0.004). Central macular thickness significantly decreased in every group throughout the follow-up period. Differences in central macular thickness between Groups A and B (P < 0.01), A and C (P < 0.01), and B and C (P < 0.01) were significant. Intraretinal cysts also significantly decreased in each group throughout the follow-up period. Differences in IC size between Groups A and B (P = 0.8), A and C (P = 0.1), and B and C (P = 0.1) were not significant. Choroidal thickness did not undergo any significant change in any group throughout the follow-up period. A significant correlation was also found in Group A between best-corrected visual acuity at month 12 and baseline central macular thickness (R = 0.3; P = 0.006), and in Group B between postoperative best-corrected visual acuity at month 12 and baseline IC size (R = 0.8; P < 0.01, negatively correlated at 92.4%). Conclusion: According to our retrospective data, diabetic macular edema with intraretinal cysts larger than 390 &mgr;m should not be treated with vitrectomy with ILM peeling, because this may induce subfoveal atrophy, defined as the “Floor Effect,” and subsequent visual deterioration.