Retinopathy Study Best-corrected Visual Acuity Research Articles

A prospective pilot study of intravitreal aflibercept for the treatment of chronic central serous chorioretinopathy: the CONTAIN study

AimTo evaluate the role of intravitreal aflibercept injection as a treatment for eyes with chronic central serous chorioretinopathy (CSCR).MethodsThis prospective pilot study enrolled 12 patients with chronic CSCR who received...

Results of intravitreal ranibizumab with a prn regimen in the treatment of extrafoveal and juxtafoveal neovascular membranes in age-related macular degeneration.

To evaluate the efficacy of intravitreal ranibizumab with a "pro re nata" regimen in the treatment of nonsubfoveal neovascular membranes secondary to age-related macular degeneration. Retrospective noncomparative case series. Thirty-one eyes with naive nonsubfoveal neovascularization secondary to age-related macular degeneration were consecutively enrolled and treated with ranibizumab intravitreal injections according to a pro re nata regimen. The follow-up was performed monthly up to 6 months and quarterly up to 2 years (25 patients). Early treatment diabetic retinopathy study best-corrected visual acuity and lesion size analysis with fluorescein angiography were recorded. The mean baseline early treatment diabetic retinopathy study best-corrected visual acuity worsened from 20/40 (0.28 logMAR) at baseline to 20/50 (0.42 logMAR) at 1-year follow-up and 20/60 (0.53 logMAR) at 2-year follow-up. The mean lesions size nearly doubled from baseline at the 2-year follow up (1.19-2.47 mm). Twenty-two patients had one or more recurrences at 1-year follow-up. All 25 patients developed a recurrence at 2 years with 7 cases developing a recurrence by 12 months. Twelve cases progressed to subfoveal lesions by the 24-month visit. Other regimens described in the literature might result in a more the satisfactory outcome using more frequent follow-up and more frequent intravitreal injections.

Intravitreal Aflibercept for Treatment-Resistant Neovascular Age-related Macular Degeneration

To assess the effectiveness of intravitreal aflibercept in patients with neovascular age-related macular degeneration (AMD) previously resistant to treatment with other anti-vascular endothelial growth factor agents. Prospective, open-label, noncontrolled, registered clinical trial. Forty-nine patients with treatment-resistant neovascular AMD. A dose of 2 mg intravitreal aflibercept was administered as 3 initial loading doses every 4 weeks (week 0, week 4, and week 8), followed by further injections every 8 weeks (weeks 16 and 24) across a 24-week period in total. All patients underwent a complete ophthalmic examination, including measurement of Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), intraocular pressure assessment, adverse event monitoring, and spectral-domain optical coherence tomography at every visit. Baseline fluorescein angiography and indocyanine green angiography also were performed. Outcomes assessed included proportions of patients with a gain or loss of more than 5 ETDRS letters and a decrease or increase in central retinal thickness (CRT) of more than 150 μm at week 24 compared with baseline, change in mean BCVA and CRT between baseline and week 24, and descriptive safety data. The BCVA improved and CRT was reduced significantly at all follow-up visits compared with baseline (P < 0.001), with a mean improvement of 6.9 letters of BCVA and a decrease of 89.4 μm in CRT at week 24. Spacing of injections from every 4 weeks to 8 weeks resulted in an increase of 37.4 μm in CRT (P < 0.001); however, this was not correlated with a significant change in vision. There was 1 (2%) patient who lost more than 5 ETDRS letters, and 27 (55%) patients who gained more than 5 letters. Two (4%) patients had a more than 150μm increase in CRT at week 24, and 10 (20%) patients showed a decrease in CRT of more than 150 μm. Intravitreal aflibercept is effective in previously treatment-resistant neovascular AMD. Further follow-up is required to determine whether these improvements can be maintained.

Electroretinographic Effects of Omega-3 Fatty Acid Supplementation on Dry Age-Related Macular Degeneration

To evaluate the effects of high-dose oral omega-3 fatty acid supplementation on electroretinography and omega-3 index in patients with dry age-related macular degeneration. Single institution, prospective, nonrandomized, noncomparative interventional case series comprising 34 eyes of 17 patients older than 50 years of age with early to intermediate age-related macular degeneration. Patients received oral supplementation with 4 g of omega-3 fatty acids daily (840 mg eicosapentaenoic acid/2520 mg docosahexaenoic acid) for 6 months. The main outcome measures included Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, change in N1 and P1 peak amplitudes on multifocal electroretinographic testing, and change in serum omega-3 index. Mean baseline Early Treatment Diabetic Retinopathy Study best-corrected visual acuity letter score was 77 letters (Snellen equivalent of 20/32). There were no statistically significant changes in visual acuity (P = .12) or retinal function by multifocal electroretinographic testing. Serum omega-3 index increased by an average of 7.6% during the course of the study (P < .001). Study limitations included the relatively short duration of the study and small number of participants. Short-term supplementation with high doses of omega-3 fatty acids does not result in any measurable changes in visual acuity or retinal function by multifocal electroretinographic testing. Dietary supplementation with 4 g of omega-3 fatty acids results in a significant increase in serum omega-3 index in patients with dry age-related macular degeneration and may provide a useful clinical measure for future studies. clinicaltrials.gov Identifier: NCT01258335.

SYSTEMIC BETA-BLOCKERS MAY REDUCE THE NEED FOR REPEATED INTRAVITREAL INJECTIONS IN PATIENTS WITH WET AGE-RELATED MACULAR DEGENERATION TREATED BY BEVACIZUMAB

To evaluate the effect of concomitant systemic therapy in patients with choroidal neovascularization secondary to age-related macular degeneration (AMD) treated by intravitreal bevacizumab and to propose a mechanism for different interindividual response. Retrospective, nonrandomized, single-center, consecutive interventional case series study. Forty-six eyes from 46 patients with choroidal neovascularization secondary to age-related macular degeneration were treated by monthly intravitreal 1.25 mg bevacizumab injections on a pro re nata regime. Patients' files were revised and changes in Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, central foveal thickness as determined by spectral domain optical coherence tomography, number of injections performed, occurrence of severe adverse effects, and systemic concomitant medication were recorded. The effect of systemic medication on final best-corrected visual acuity, central foveal thickness, and number of injections performed was evaluated. The most frequent systemic medications recorded were angiotensin-converting-enzyme inhibitors in 19 patients, beta-adrenergic blocking agents (n = 18), nonsteroidal antiinflammatory drugs (n = 17), diuretics (n = 16), calcium channel blockers (n = 14), benzodiazepines (n = 11), proton-pump inhibitors (n = 9), and statins (n = 8). Thirty-two patients had arterial hypertension. Average follow-up was 25.1 months (standard deviation [SD] = 8.9). Average gain in best-corrected visual acuity was 0.9 (SD = 13.6) and -2.1 letters (SD = 15.9) at 12 months and 24 months, respectively. The average reduction in central foveal thickness was 111 μm (SD = 54) and 105 μm (SD = 71) at 12 months and 24 months, respectively. The average number of intravitreal injections required was 6.7 (SD = 3.2). Patients on treatment with systemic beta-adrenergic blocking agents required less intravitreal injections (5.2, SD = 2.4 vs. 7.9, SD = 3.4) and this difference was statistically significant (P = 0.0068, multiple linear regression). Concomitant systemic beta-adrenergic blocking agents treatment may reduce the need for repeated intravitreal injections of bevacizumab in patients with choroidal neovascularization associated with age-related macular degeneration.

INTRAVITREAL BEVACIZUMAB PLUS GRID LASER PHOTOCOAGULATION OR INTRAVITREAL BEVACIZUMAB OR GRID LASER PHOTOCOAGULATION FOR DIFFUSE DIABETIC MACULAR EDEMA

To evaluate the anatomical and functional outcomes at 24 months in patients with diffuse diabetic macular edema treated with primary intravitreal bevacizumab (IVB) plus grid laser photocoagulation (GLP) or primary IVB alone or GLP alone. Retrospective, interventional, comparative, multicenter study. We included in this analysis 141 eyes of 120 patients with diffuse diabetic macular edema treated with primary IVB alone (Group A), 120 eyes of 94 patients with GLP therapy (Group B), and 157 eyes of 104 patients treated with IVB plus GLP (Group C). In all 3 groups, the authors observed improvement of Early Treatment Diabetic Retinopathy Study best-corrected visual acuity from baseline to 24-month follow-up (P < 0.0001). The improvement rate in Group A was statistically significantly better than in Group B (analysis of variance, P = 0.013). The authors also found a decrease in central macular thickness in all groups from baseline to the 24-month follow-up (P < 0.0001). The comparison among 3 groups showed higher central macular thickness decrease in Group A than in Groups B and C (analysis of variance, P < 0.001). The study provides evidence to support the use of primary IVB with or without GLP as treatment of diffuse diabetic macular edema. Primary IVB without GLP seems to be superior to GLP alone to provide stability or improvement in best-corrected visual acuity in patients with diffuse diabetic macular edema at 24 months.

Three‐year results of visual outcome with disease activity–guided ranibizumab algorithm for the treatment of exudative age‐related macular degeneration

To evaluate 3-year follow-up treatment outcomes with ranibizumab (Lucentis(®)) 0.5 mg administered either monthly or quarterly on a pro re nata (PRN) basis according to a disease activity-guided monitoring and treatment algorithm. A total of 316 treatment-naive eyes of 316 patients with exudative age-related macular degeneration met the criteria for inclusion in this retrospective, interventional case series. Patients were treated with ranibizumab 0.5 mg according to a disease activity-guided algorithm with monthly monitoring. Optical coherence tomography and fluorescein angiography were routinely used to assess disease activity: active lesions were treated with a series of three monthly injections, whereas inactive lesions were treated with quarterly injections. Mean Early Treatment Diabetic Retinopathy Study best-corrected visual acuity improved from 52 letters at baseline to 59 letters at 12 months, achieved with a mean of 7.1 injections, 61 letters at 24 months with a mean of 5.0 injections administered in the second year and 60 letters at 36 months with a mean number of 5.2 injections. Monthly visits and a morphology-driven PRN regimen with 3 injections in case of recurrence plus quarterly injections in case of inactive CNV resulted in an average VA gain of 7-9 letters that could be maintained over 3 years.

Risk Factors for Conversion to Neovascular Age-related Macular Degeneration Based on Longitudinal Morphologic and Visual Acuity Data

To use longitudinal quantitative morphologic and visual acuity (VA) data to investigate the risk of choroidal neovascularization (CNV) event occurrence in eyes with dry age-related macular degeneration (AMD). Prospective observational study. A total of 513 participants (844 eyes) followed longitudinally in one center enrolled in the Age-Related Eye Disease Study (AREDS) or the Prophylactic Treatment of AMD Study (PTAMD). We assessed images of previously obtained fundus photographs for the presence of macular pigmentation, drusen area, and drusen distribution (number and size), and fellow eye CNV status at baseline. Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity at each visit and the age of each subject were obtained. We used a longitudinal logistic mixed-effects model with random intercepts fitted to event occurrences to assess risk on a per eye basis. Odds ratios for CNV event. Thirty-one subjects (6.0%) had events. Only VA changes over time and follow-up interval showed statistically significant effects. Several statistical models that included VA at the previous visit were used. In 2 models, 3 categories of VA were used: ≤ 75 letters, >75 and ≤ 85 letters, and >85 letters. Two categories were used for follow-up: ≤ 3 years versus >3 years or ≤ 1 year versus >1 year. In the first model with categorization at 3 years, a decrease in acuity from the >85 letter category to ≤ 75 letters increased the odds of CNV by 16.9 times (P = 0.022). In the model with categorization at 1 year, a decrease in acuity from the >85-letter category to ≤ 75 letters increased the odds of CNV by 21.4 times (P = 0.0175). Differences between the follow-up intervals were significant (P = 0.043) and indicated a more than 7-fold increase in the odds. Changes in morphologic features of the macula did not show significant effects. A decrease in VA to ≤ 75 ETDRS letters in an eye with an initial ETDRS baseline acuity of >85 letters increases the likelihood of CNV by approximately 20-fold. This likelihood also increases with aging.

PROSPECTIVE RANDOMIZED CONTROLLED TRIAL OF COMBINATION RANIBIZUMAB (LUCENTIS) AND BROMFENAC (XIBROM) FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION

To evaluate whether bromfenac eyedrops and ranibizumab intravitreal injections would provide added efficacy over ranibizumab alone. This was a single-site, multiinvestigator, prospective, open-label, interventional, Phase II study of patients with new or recurrent exudative/neovascular age-related macular degeneration. Thirty eyes were enrolled consecutively and were randomized in a ratio of 2:1 to combination therapy with intravitreal ranibizumab and topical bromfenac, and ranibizumab alone. All patients received ranibizumab monthly therapy for 4 months then as needed monthly in accordance with standard of care. Patients receiving bromfenac self-administered 1 drop twice a day for 12 months. Patients were followed for 12 months. There were no safety concerns with the combination therapy. No statistically significant differences were identified in Early Treatment Diabetic Retinopathy Study best-corrected visual acuity or the number of injections required. However, the mean 12-month change in central macular thickness in the combination group was -81.56 μm while in the ranibizumab group alone the change was -42.50 μm (P = 0.03). The proportion of eyes experiencing a decrease in CMT of 50 μm or more was also significantly higher in those receiving combination therapy (P = 0.046). This pilot study is the first to prospectively identify a biologic signal that may indicate combination therapy with an easily administered well-tolerated eyedrop and ranibizumab is efficacious for the treatment of neovascular age-related macular degeneration. Further studies are warranted to validate this finding.

Short‐term progression of wet AMD and correlation with 1‐year treatment results

Quantification of short-term progression of active neovascular age-related macular degeneration and correlation with 1-year outcome. Sixty-five patients with newly diagnosed treatment-naive active subfoveal choroidal neovascularization (CNV), who had participated in clinical trials testing anti-vascular endothelial growth factor therapy, were retrospectively assessed. Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), Spectral Domain Optical Coherence Tomography (SD-OCT) and fluorescein angiography (FA) were performed twice during the pretreatment period. Changes in BCVA, central retinal thickness (CRT), average macular thickness (AMT) and leakage area were documented within this pretreatment period for all patients and for lesion type I (occult CNV, n=42) and type II (classic CNV, n=23). Three-month and 1-year BCVA were then correlated with the pretreatment period. The pretreatment period was 19±3 days (range: 2-108). Neither type I nor type II lesions showed a significant BCVA decrease or CRT/AMT increase during this period. On FA, mean leakage area increased significantly during the pretreatment period: in the pooled group from 5.50±0.62 (screening) to 7.60±0.86 mm2 (baseline) (p<0.0001), in type II from 4.65±0.90 to 7.83±1.62 mm2 (p<0.01) and in type I from 6.08±0.85 to 7.45±0.96 mm2 (p<0.0001). The mean increase in leakage area per day was 0.046±0.02 mm2, p=0.034. Type II showed a daily growth of 0.09±0.08 mm2 (p<0.042) and type I 0.045±0.008 mm2 per day (p<0.0001). However, neither leakage area increase nor pretreatment period was correlated with 3-month or 1-year BCVA outcome. SD-OCT and BCVA testing did not reveal deterioration during the pretreatment period. However, the leakage area progressed rapidly. Despite the rapid increasing leakage area, the 19-day waiting period was not associated with a poorer visual outcome at 3 months and 1 year.

HORIZON: An Open-Label Extension Trial of Ranibizumab for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration

To evaluate the long-term safety and efficacy of multiple intravitreal ranibizumab injections (Lucentis, Genentech, Inc., South San Francisco, CA) administered at the investigator's discretion in patients with choroidal neovascularization secondary to age-related macular degeneration. An open-label, multicenter, extension study. Patients who completed the controlled treatment phase of 1 of 3 prospective, randomized, 2-year clinical trials of ranibizumab were eligible for enrollment. Analyses were performed for 3 groups: (1) patients treated with ranibizumab in the initial study (ranibizumab treated-initial; n = 600); (2) patients randomized to control who crossed over to receive ranibizumab (ranibizumab treated-XO; n = 190); and (3) ranibizumab-naïve patients (ranibizumab untreated; n = 63). Ranibizumab 0.5 mg was administered at the investigator's discretion. Adverse events (AEs) and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) assessments were conducted at study visits every 3 to 6 months. Incidence and severity of AEs. There was 1 occurrence of mild endophthalmitis per 3552 HORIZON injections in the ranibizumab treated-initial/ranibizumab treated-XO groups. There were no serious AE reports of lens damage, retinal tears, or rhegmatogenous retinal detachments in the study eyes. The proportion of patients with any single postdose intraocular pressure ≥30 mmHg was 9.2%, 6.6%, and 0%, and the proportion of patients with glaucoma was 3.2%, 4.2%, and 3.2% in the ranibizumab treated-initial, ranibizumab treated-XO, and ranibizumab untreated groups, respectively. Cataract AEs were less frequent in the ranibizumab untreated group: 6.3% versus 12.5% and 12.1% in the ranibizumab treated-initial and ranibizumab treated-XO groups, respectively. The proportion of patients with arterial thromboembolic events as defined by the Antiplatelet Trialists' Collaboration was 5.3% in the ranibizumab treated-initial and ranibizumab treated-XO groups, and 3.2% in the ranibizumab untreated group. At month 48 (2 years of HORIZON), the mean change in BCVA (ETDRS letters) relative to the initial study baseline was 2.0 in the ranibizumab treated-initial group versus -11.8 in the pooled ranibizumab treated-XO and ranibizumab untreated groups. Multiple ranibizumab injections were well tolerated for ≥4 years. With less frequent follow-up leading to less treatment, there was an incremental decline of the visual acuity (VA) gains achieved with monthly treatment. Proprietary or commercial disclosure may be found after the references.

Epimacular brachytherapy for the treatment of retinal angiomatous proliferation.

The purpose of this study was to present a case of a retinal angiomatous proliferation (RAP) treated with epimacular brachytherapy that was refractory to continued ranibizumab therapy. An interventional case report of an 89-year-old woman with angiographically confirmed RAP had shown a poor response to 8 anti-vascular endothelial growth factor (anti-vascular endothelial growth factor) retreatment injections over a 10-month period. The patient underwent pars plana vitrectomy combined with beta irradiation of the RAP lesion using a Strontium-90 applicator (NeoVista). The device was positioned over the lesion to deliver 24 gray over 4.5 minutes. Early Treatment Diabetic Retinopathy Study best-corrected visual acuity with full refraction was undertaken monthly by trial-certified examiners, independent of the operating surgeon. The main outcome measures were Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, central retinal thickness measured by optical coherence tomography, and the number of anti-vascular endothelial growth factor retreatments. Preoperative best-corrected visual acuity was 53 letters (20/80), improving to 69 letters (20/50) at 12 months and 71 letters (20/40) at 21 months. Only one ranibizumab retreatment was required, at Month 2. Optical coherence tomography central retinal thickness reduced from 312 μm to 224 μm with a return of the normal foveal contour. There was full regression of the RAP lesion on clinical examination, with a reduction in lesion activity demonstrated by fundus fluorescein angiography. This is the first reported case of RAP treated with epimacular brachytherapy, with encouraging results. Epimacular brachytherapy may be a new treatment option for refractory RAP lesions requiring frequent intravitreal ranibizumab, but further studies are needed.

CORRELATION BETWEEN SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS AND VISUAL OUTCOME AFTER PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT REPAIR

To correlate the postoperative visual outcome with the spectral-domain optical coherence tomography (SD-OCT) findings in the fovea after successful rhegmatogenous retinal detachment repair. Cross-sectional, observational study. Thirty-five patients with preoperative macula-on rhegmatogenous retinal detachment (12 eyes) and macula-off rhegmatogenous retinal detachment (23 eyes) who underwent scleral buckling surgery for primary rhegmatogenous retinal detachment were recruited. Early Treatment Diabetic Retinopathy Study best-corrected visual acuity measurement, microperimetry, and SD-OCT examination were performed on the same day. Foveal center retinal thickness, central 1-mm subfield thickness, and outer nuclear layer thickness were measured using SD-OCT. The presence or absence of epiretinal membrane, intraretinal fluid, and subretinal fluid was assessed. The status of the external limiting membrane, inner/outer segment junction, and intermediate line was also evaluated and judged as disrupted or complete. The correlations between SD-OCT findings and either postoperative best-corrected visual acuity or retinal sensitivities for central 12° were analyzed. The outer nuclear layer thickness was the only significant SD-OCT retinal measurement strongly correlated with both postoperative best-corrected visual acuity (r = 0.61; P < 0.001) and retinal sensitivities for central 12° (r = 0.53; P = 0.001). Among the SD-OCT imaging findings, status of the external limiting membrane, inner/outer segment junction, and intermediate line and the presence of intraretinal fluid showed a significantly high correlation either with best-corrected visual acuity outcome (r = -0.60; P < 0.001, r = -0.63; P < 0.001, r = -0.66; P < 0.001, and r = -0.50; P = 0.002, respectively) or with postoperative retinal sensitivities (r = -0.59; P < 0.001, r = -0.61; P < 0.001, r = -0.66; P < 0.001, r = -0.50; P = 0.002, respectively). Multivariate analysis showed that the outer nuclear layer thickness and the status of the intermediate line were the most important predictors of visual outcome (P < 0.001 and P < 0.001, respectively). This study showed that not only the status of the external limiting membrane and the inner/outer segment junction but also the integrity of the intermediate line and the outer nuclear layer thickness changes may be important predictors of postoperative visual outcome after anatomically successful rhegmatogenous retinal detachment repair.

INTRAVITREAL RANIBIZUMAB FOR MACULAR EDEMA SECONDARY TO CENTRAL RETINAL VEIN OCCLUSION

To evaluate the safety and efficacy of intravitreal ranibizumab for macular edema secondary to central retinal vein occlusion. Patients with macular edema secondary to perfused central retinal vein occlusion were enrolled in this ongoing, prospective, open-label study. Treatment was initiated with monthly intravitreal ranibizumab for 3 months. In the first year, additional injections were administered for edema in quarterly intervals as needed (PRN) for Cohort 1 (n = 10) and monthly PRN for Cohort 2 (n = 10). In the second year of treatments, all patients received monthly PRN treatment. Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, central retinal thickness, fundus photographs, and fluorescein angiograms were evaluated, and the incidence and severity of adverse events were documented. Mean change in best-corrected visual acuity and central retinal thickness improved during the induction phase in both groups. During the remainder of the first year for Cohort 1, initial gains were lost during quarterly treatment but returned with monthly PRN treatment in the second year. For Cohort 2, improvement in best-corrected visual acuity and central retinal thickness from the induction phase was maintained through Month 24. Nineteen of 20 patients experienced a reduction in intraretinal hemorrhage, optic nerve swelling, and/or venous diameter after treatment. One myocardial infarction, one cerebrovascular accident, and no serious ocular adverse events were reported. Iris neovascularization was developed in none of the eyes. Ranibizumab was well tolerated and associated with a greater reduction in macular edema and improvement in visual acuity in the monthly PRN regimen compared with quarterly treatment. Vision lost during the quarterly PRN injection intervals in the first year of Cohort 1 could be regained by switching to monthly PRN dosing.

INTRAVITREAL INJECTION OF AUTOLOGOUS BONE MARROW–DERIVED MONONUCLEAR CELLS FOR HEREDITARY RETINAL DYSTROPHY

To evaluate the short-term (10 months) safety of a single intravitreal injection of autologous bone marrow-derived mononuclear cells in patients with retinitis pigmentosa or cone-rod dystrophy. A prospective, Phase I, nonrandomized, open-label study including 3 patients with retinitis pigmentosa and 2 patients with cone-rod dystrophy and an Early Treatment Diabetic Retinopathy Study best-corrected visual acuity of 20/200 or worse. Evaluations including best-corrected visual acuity, full-field electroretinography, kinetic visual field (Goldman), fluorescein and indocyanine green angiography, and optical coherence tomography were performed at baseline and 1, 7, 13, 18, 22, and 40 weeks after intravitreal injection of 10 × 10(6) autologous bone marrow-derived mononuclear cells (0.1 mL) into 1 study eye of each patient. No adverse event associated with the injection was observed. A 1-line improvement in best-corrected visual acuity was measured in 4 patients 1 week after injection and was maintained throughout follow-up. Three patients showed undetectable electroretinography responses at all study visits, while 1 patient demonstrated residual responses for dark-adapted standard flash stimulus (a wave amplitude approximately 35 μV), which remained recordable throughout follow-up, and 1 patient showed a small response (a wave amplitude approximately 20 μV) recordable only at Weeks 7, 13, 22, and 40. Visual fields showed no reduction (with a Goldman Standard V5e stimulus) for any patient at any visit. No other changes were observed on optical coherence tomography or fluorescein and indocyanine green angiograms. Intravitreal injection of autologous bone marrow-derived mononuclear cells in eyes with advanced retinitis pigmentosa or cone-rod dystrophy was associated with no detectable structural or functional toxicity over a period of 10 months. Further studies are required to investigate the role, if any, of autologous bone marrow-derived mononuclear cell therapy in the management of retinal dystrophies.

Intravitreal Bevacizumab for Subfoveal Choroidal Neovascularization in Age-Related Macular Degeneration at Twenty-four Months: The Pan-American Collaborative Retina Study

To report the 24-month anatomic and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (IVB) (Avastin; Genentech Inc., San Francisco, CA) (1.25 or 2.5 mg) in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Retrospective, multicenter, interventional, comparative case series. We reviewed the clinical records of 180 consecutive patients (207 eyes) with subfoveal CNV secondary to AMD at 9 centers from 8 countries. Patients were treated with at least 1 injection of IVB 1.25 mg (124 eyes [59.9%]) or 2.5 mg (83 eyes [40.1%]). Patients underwent ETDRS BCVA testing, ophthalmoscopic examination, optical coherence tomography (OCT), and fluorescein angiography (FA) at baseline and 1-, 3-, 6-, 12-, and 24-month visits. Changes in BCVA and OCT. The mean age of our patients was 74.3±7.5 years. The mean number of IVB injections per eye was 5.1 (range, 1-24 injections). In the 1.25 mg group, baseline BCVA improved from 20/235 (logarithm of the minimum angle of resolution [logMAR] 1.07) to 20/172 (logMAR 0.92) at 24 months (P<0.0001). Similar BCVA changes were observed in the 2.5 mg group. At baseline, the mean central macular thickness (CMT) by OCT in the 1.25 mg group was 308.4±127.52 μm, which was reduced to 269.35±97.92 μm, 262.1±94.81 μm, 264.03±97.06 μm, 245.91±89.52 μm, and 249.27±89.14 μm at 1, 3, 6, 12, and 24 months, respectively (P<0.0001). Similar changes were observed in the 2.5 mg group. In the 2.5 mg group, systemic complications included 2 new cases (2.6%) of arterial hypertension, 1 case (1.3%) of stroke, and 1 case (1.3%) of death. Primary IVB at a dose of 1.25 or 2.5 mg seems to provide stability or improvement in BCVA, OCT, and FA in subfoveal CNV secondary to AMD at 24 months. Our results show no significant difference regarding BCVA with IVB at doses of 1.25 or 2.5 mg.

Intravitreal Clindamycin and Dexamethasone for Zone 1 Toxoplasmic Retinochoroiditis at Twenty-four Months

To report the anatomic and functional outcomes of intravitreal clindamycin and dexamethasone for the treatment of zone 1 toxoplasmic retinochoroiditis (TRC). Patients had 1 or more of the following indications for local therapy: intolerance to oral medication, contraindication to oral medication because of pregnancy, lack of response despite oral antimicrobial treatment, or treatment with concomitant oral and local therapy to avoid or limit foveal or optic disc involvement. Noncomparative, retrospective, multicentric interventional case series. We reviewed the medical records of 12 consecutive patients (eyes) with posterior pole (zone 1) TRC who were treated weekly or every 4 weeks (during pregnancy) with intravitreal injections of clindamycin (1.5 mg/0.1 ml) and dexamethasone (400 microg/0.1 ml). Ophthalmic evaluation included Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA); assessment of central macular thickness (CMT); resolution of inflammation by optical coherence tomography (OCT), clinical examination, and fluorescein angiography; and assessment of adverse events. Patients were followed for 24 months. Resolution of TRC, changes in BCVA, and OCT. Resolution of TRC was achieved in all cases with a mean number of injections of 3.6 (range: 2-5 injections) with a mean interval of 15.5+/-4 days. At 24 months a significant reduction in CMT by OCT was observed, from 387.6+/-70.1 microm to 185.2+/-44.7 microm (P = 0.0004). Baseline BCVA was logarithm of the minimal angle of resolution (logMAR) 1+/-0.4 (20/200), which improved to 0.5+/-0.4 (20/63) (P = 0.002) at the end of follow-up. Ten eyes (83.3%) improved > or =2 ETDRS lines of BCVA, and 2 eyes (20%) remained stable at 24 months. One patient's vision was limited because of macular scarring. No ocular or systemic adverse events were observed. No recurrences at 24 months of follow-up were observed. The combination of intravitreal clindamycin and dexamethasone was associated with resolution of zone 1 TRC and functional and anatomic improvement in patients who did not tolerate, had contraindications to, or did not respond to oral medications.

A RANDOMIZED, DOUBLE-MASKED CONTROLLED CLINICAL TRIAL OF SANDOSTATIN LONG-ACTING RELEASE DEPOT IN PATIENTS WITH POSTSURGICAL CYSTOID MACULAR EDEMA

The purpose of this study was to evaluate the safety and efficacy of octreotide, a somatostatin analog, for treatment of postsurgical cystoid macular edema. Twenty-one patients with chronic, refractory postsurgical cystoid macular edema and Early Treatment Diabetic Retinopathy Study best-corrected visual acuity of 20/25 to 20/400 were randomized 2:1 to 30 mg monthly intramuscular octreotide or placebo. Outcome measures were visual acuity (primary) and macular thickness and fluorescein angiographic leakage (secondary). Fourteen eyes received octreotide and seven eyes received placebo. Mean duration of cystoid macular edema was 2.65 and 1.99 years for Sandostatin long-acting release and placebo groups, respectively. Visual acuity at 6 months improved > or =2 lines in 7 of 14 eyes (50%) in the treatment group and 0 of 7 eyes in the placebo group (P = 0.046). Improvement in retinal thickening and angiographic leakage occurred in 3 of 13 eyes (23.1%) and 3 of 14 eyes (21.4%) of the treatment group, respectively, and in 1 of 7 eyes (14.3%) (P = 1.0 compared with the treatment group) and 0 of 7 eyes in the placebo group (P = 0.52 compared with the treatment group). The three eyes that improved in all parameters were treated with octreotide. Although there were no statistically significant differences between both groups in retinal thickening or angiographic leakage, octreotide-treated patients were more likely to experience a > or =2-line improvement in visual acuity. However, this observation cannot be generalized because of the small sample size.

Primary Intravitreal Bevacizumab for Diffuse Diabetic Macular Edema: The Pan-American Collaborative Retina Study Group at 24 Months

To report the 24-month anatomic and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (Avastin; Genentech, Inc., San Francisco, CA; 1.25 or 2.5 mg) in patients with diffuse diabetic macular edema (DDME). In addition, a comparison of the 2 different doses of intravitreal bevacizumab (IVB) used is presented. Retrospective, multicenter, interventional, comparative case series. The clinical records of 115 consecutive patients (139 eyes) with DDME at 11 centers from 8 countries were reviewed. Patients were treated with at least 1 intravitreal injection of 1.25 or 2.5 mg of bevacizumab. All patients were followed up for 24 months. Patients underwent ETDRS BCVA testing, ophthalmoscopic examination, optical coherence tomography (OCT), and fluorescein angiography (FA) at the baseline, 1-, 3-, 6-, 12-, and 24-month visits. Changes in BCVA and OCT results. The mean age of the patients was 59.4+/-11.1 years. The mean number of IVB injections per eye was 5.8 (range, 1-15 injections). In the 1.25-mg group at 1 month, BCVA improved from 20/150 (0.88 logarithm of the minimum angle of resolution [logMAR] units) to 20/107, 0.76 logMAR units (P<0.0001). The mean BCVA at 24 months was 20/75 (0.57 logMAR units; P<0.0001). Similar BCVA changes were observed in the 2.5-mg group: at 1 month, BCVA improved from 20/168 (0.92 logMAR units) to 20/118 (0.78 logMAR units; P = 0.02). The mean BCVA at 24 months was 20/114 (0.76 logMAR units; P<0.0001). In the 1.25-mg group, the mean central macular thickness (CMT) decreased from 466.5+/-145.2 microm at baseline to 332.2+/-129.6 microm at 1 month and 286.6+/-81.5 microm at 24 months (P<0.0001). Similar results were obtained in the 2.5-mg group. Primary IVB at doses of 1.25 to 2.5 mg seem to provide stability or improvement in BCVA, OCT, and FA in DDME at 24 months. The results show no evident difference between IVB at doses of 1.25 or 2.5 mg.

Intravitreal Bevacizumab for Treatment of Chronic Central Serous Chorioretinopathy

To evaluate the short-term safety and efficacy of intravitreal bevacizumab for the treatment of intraretinal or subretinal fluid accumulation secondary to chronic central serous chorioretinopathy (CSC). Twelve patients were treated with intravitreal injections of 2.5 mg bevacizumab at 6- to 8-week intervals until intraretinal or subretinal fluid resolved. Observation procedures were Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), ophthalmic examination, and optical coherence tomography (OCT), performed at 6- to 8-week intervals. Fluorescein angiography was performed at baseline visit and thereafter depending on clinical and OCT findings. Multivariate analysis of variance with repeated measures was used to calculate a statistical significance of change in BCVA and mean central retinal thickness, which were the main outcome measures. SAS statistical software was used for analyses. Patients received 2-/+1 intravitreal injections of bevacizumab on average during a follow-up of 24-/+14 weeks. Mean BCVA increased by 2-/+2 lines; the change in BCVA (logMAR) was significant (p<0.02). Mean central retinal thickness decreased significantly over follow-up (p<0.05), with 6 patients (50%) showing complete resolution of subretinal fluid. Anatomic and functional improvement following intravitreal bevacizumab injections suggest that vascular endothelial growth factor (VEGF) may be involved in fluid leakage in patients with chronic CSC. The results suggest a possible role for anti-VEGF agents in the treatment of chronic CSC. Further evaluation of intravitreal bevacizumab for chronic CSC in controlled randomized studies is warranted.