THE LATEST PUBLISHED RESEARCH

Intravitreal Triamcinolone for Vision Loss Associated with Macular Edema Secondary to CRVO
Investigators compared the efficacy and safety of 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone with observation for eyes with vision loss associated with macular edema secondary to perfused central retinal vein occlusion (CRVO) in this multicenter, randomized, clinical trial of 271 participants. The main outcome measure was a gain in visual acuity letter score of 15 or more from baseline to month 12.

According to the investigators, 7%, 27% and 26% of participants achieved the primary outcome in the observation, 1-mg and 4-mg groups, respectively. The odds of achieving the primary outcome were 5.0 times greater in the 1-mg group than the observation group (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.8-14.1; p=.001) and 5.0 times greater in 4-mg group than the observation group (OR, 5.0;95% CI, 1.8-14.4; p=.001). There was no difference identified between the 1-mg and 4-mg groups (OR, 1.0; 95% CI, 0.5-2.1; p=.97). Additionally, the rates of elevated IOP and cataract were smaller for the observation and 1-mg groups, but higher in the 4-mg group.

Intravitreal triamcinolone is superior to observation for treating vision loss associated with macular edema secondary to CRVO in patients who have characteristics similar to those in the SCORE-CRVO trial. The study investigators determined that the 1-mg does has a safety profile superior to that of the 4-mg dose.

Source: The SCORE Study Research Group. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with observation to treat vision loss associated with macular edema secondary to central retinal vein occlusion: The Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study Report 5. Arch Ophthalmol. 2009;127(9):1101-1114.

Comparison of Intravitreal Triamcinolone to Standard Care for Treating Vision Loss Associated with Macular Edema Secondary to BRVO
The authors of this multicenter, randomized clinical trial of 411 participants compared the efficacy and safety of 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone with standard care (grid photocoagulation in eyes without dense macular hemorrhage and deferral of photocoagulation until hemorrhage clears in eyes with dense macular hemorrhage) for eyes with vision loss associated with macular edema secondary to branch retinal vein occlusion (BRVO). Gain in visual acuity letter score of 15 or more from baseline to month 12 served as the main outcome measure.

A total of 29%, 26% and 27% of participants achieved the primary outcome in standard care, 1-mg and 4-mg groups, respectively, reported the authors. None of the pairwise comparisons between the 3 groups was statistically significant at month 12 and the rates of elevated IOP and cataract were similar for the standard care and 1-mg groups, but higher in the 4-mg group.

The study authors identified no difference in visual acuity at 12 months for the standard care group compared with the triamcinolone groups; however, rates of adverse events (particularly elevated IOP and cataract) were highest in the 4-mg group. They noted that application to Clinical Practice Grid photocoagulation as applied in the SCORE Study remains the standard care for patients with vision loss associated with macular edema secondary to BRVO who have characteristics similar to participants in the SCORE-BRVO trial. Furthermore, they concluded that grid photocoagulation should remain the benchmark against which other treatments are compared in clinical trials for eyes with vision loss associated with macular edema secondary to BRVO.

Source: The SCORE Study Research Group. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associated with macular edema secondary to branch retinal vein occlusion: The Standard Care vs Coritcosteroid for Retinal Vein Occlusion (SCORE) Study Report 6. Arch Ophthalmol 2009;127(9):1115-1128.

Management of Branch and Hemiretinal Vein Occlusion with Intravitreal Bevacizumab
To evaluate the safety and efficacy of intravitreal bevacizumab for the treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO) and hemiretinal vein occlusion (HRVO), a retrospective review was performed of consecutive patients treated with intravitreal bevacizumab (1.25 mg) for ME secondary to BRVO/HRVO from May 2005 to August 2006 with follow up through February 2007. Re-treatment was performed at monthly or longer intervals at the discretion of the treating physician.

A total of 52 eyes with a BRVO and 13 eyes with an HRVO received intravitreal bevacizumab at baseline. It was noted that isual acuity improved by a mean of 12 letters at 1 month (n=51; p<0.001), 13 letters at 3 months (n=61; p<0.001), 13 letters at 6 months (n=42; p<0.001), 14 letters at 9 months (n=27; p<0.001) and 15 letters at 12 months (n=17; p=0.015). The mean optical coherence tomography (OCT) thickness decreased by 184 µm (p<0.001), 131 µm (p<0.001), 161 µm (p<0.001), 158 µm (p=0.002) and 205 µm (p=0.002) at 1 month, 3 months, 6 months, 9 months and 12 months, respectively. The mean number of injections was 1.4, 2.1, 2.7 and 3.1, and 3.3 at 1 month, 3 months, 6 months, 9 months and 12 months, respectively. Additionally, no ocular or systemic adverse events were observed.

Improvements in visual acuity and OCT outcomes were observed during the first year after intravitreal bevacizumab in patients with ME secondary to BRVO and HRVO.

Source: Gregori NZ, Rattan GH, Rosenfeld PJ, et al. Safety and efficacy of intravitreal bevacizumab (Avastin) for the management of branch and hemiretinal vein occlusion. Retina 2009;29(7):913-925.

Comparison of Intravitreal Treatments for Neovascular AMD
Researchers compared outcomes after switching from intravitreal bevacizumab to ranibizumab in patients with neovascular AMD and found that in this subset of patients with neovascular AMD switched from bevacizumab to ranibizumab therapy, there were no apparent differences in visual acuity outcomes or injection rates.

They performed a retrospective review of patients with neovascular AMD who were switched from treatment with intravitreal bevacizumab to intravitreal ranibizumab once ranibizumab became commercially available. All reviewed patients had at least three bevacizumab injections before being switched to ranibizumab. According to the researchers, the treatment outcomes included comparisons of visual acuity and dosing frequency while receiving both drugs.

A total of 84 eyes met the inclusion criteria. The study researchers noted that mean baseline visual acuity was 20/100+1 and that mean duration of bevacizumab treatment was 7.1 months followed by 7.3 months with ranibizumab (p=0.68). Moreover, best-obtained visual acuity during treatment was 20/63+1 with bevacizumab and 20/63+2 with ranibizumab (p=0.5). Last mean visual acuity after receiving bevacizumab at the time of the first ranibizumab injection was 20/80. Lastly, the researchers determined that mean visual acuity at the last ranibizumab follow-up visit was 20/80+1 (p=0.49) and that mean injection rates per month while receiving bevacizumab and ranibizumab were 0.66 (p=0.98). They noted that larger prospective studies are underway to directly compare these drugs for the treatment of neovascular AMD.

Source: Stepien KE, Rosenfeld PJ, Puliafito CA, et al. Comparison of intravitreal bevacizumab followed by ranibizumab for the treatment of neovascular age-related macular degeneration. Retina 2009;29(8):1067-1073.

Ranibizumab's Effect on Neovascular AMD
This 12-month, randomized (cohort 1) or open-label (cohort 2) multicenter clinical trial evaluated the safety and efficacy of intravitreal ranibizumab in a large population of subjects with neovascular AMD. The trial included 4,300 subjects with angiographically determined subfoveal choroidal neovascularization (CNV) secondary to AMD.

Cohort 1 subjects were randomized 1:1 to receive 0.3 mg (n=1,169) or 0.5 mg (n=1,209) intravitreal ranibizumab for 3 monthly loading doses. Dose groups were stratified by AMD treatment history (treatment-naïve vs. previously treated). Cohort 1 subjects were retreated on the basis of optical coherence tomography (OCT) or visual acuity (VA) criteria and Cohort 2 subjects (n=1,922) received an initial intravitreal dose of 0.5 mg ranibizumab and were retreated at physician discretion Safety was evaluated at all visits and safety outcomes included the incidence of ocular and nonocular adverse events (AEs) and serious adverse events (SAEs). Efficacy outcomes included changes in best-corrected visual acuity (BCVA) over time.

Roughly 81.7% of Cohort 1 subjects and 49.9% of Cohort 2 subjects completed the 12-month study. It was noted that the average total number of ranibizumab injections was 4.9 for Cohort 1 and 3.6 for Cohort 2. The incidence of vascular and nonvascular deaths during the 12-month study was 0.9% and 0.7% in the Cohort 1 0.3 mg group, 0.8% and 1.5% in the Cohort 1 0.5 mg group and 0.7% and 0.9% in Cohort 2, respectively. The incidence of death due to unknown cause was 0.1% in both Cohort 1 dose groups and Cohort 2. It was observed that the number of vascular deaths and deaths due to unknown cause did not differ across cohorts or dose groups. Stroke rates were 0.7%, 1.2% and 0.6% in the 0.3 mg and 0.5 mg groups and Cohort 2, respectively. Moreover, at month 12, Cohort 1 treatment-naïve subjects had gained an average of 0.5 (0.3 mg) and 2.3 (0.5 mg) VA letters and previously treated subjects had gained 1.7 (0.3 mg) and 2.3 (0.5 mg) VA letters.

Intravitreal ranibizumab was found to be safe and well tolerated in a large population of subjects with neovascular AMD and ranibizumab had a beneficial effect on VA. Future investigations will seek to establish optimal dosing regiments for persons with neovascular AMD.

Source: Boyer DS, Heier JS, Brown DM, et al. A phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration. Ophthalmology 2009;116(9):1731-1339.

Ranibizumab for Exudative AMD: 1-Year Results
To evaluate the results of one year of treatment with intravitreal ranibizumab for exudative AMD in a clinical setting, scientists conducted a nonrandomized, single-center, retrospective, interventional case series.

The series included a retrospective analysis of consecutive charts and angiograms of 122 patients (85 women [70%] and 37 men ranging in age from 56 to 91 years [mean ± standard deveiation, 78.3 ± 7]) with previously untreated exudative AMD, treated in one or both eyes with ranibizumab between January 2 and October 31, 2007. The scientists recorded the following for each patient: age at presentation, gender, treated eye, type of choroidal neovascularization, visual acuity (VA) measured on an Early Treatment Diabetic Retinopathy Study (ETDRS) chart at baseline and at 52 ± 6 weeks, the number of performed intravitreal (IVT) injections and follow-up examinations. In all, 124 eyes were treated on a pro re nata basis after 1 or 3 initial IVT injections. The mean number of IVT injections was 3.79 ± 1.39 (range, 1 to 7) and the mean number of follow-up visits was 8.07 ± 1.44 (range, 4 to 12). Furthermore, mean VA ± standard deviation changed from 56.15 ± 14 to 56.89 ± 17 letters (VA gain, +0.7 letters).

The findings of this case series showed that VA stabilized rather than improved and compared unfavorably with the gains found in randomized clinical trials and the Prospective Optical Coherence Tomography Imaging of Patients with Neovascular AMD Treated with intraOcular Ranibizumab (PrONTO) Study. Patients in this study, however, were examined less frequently and were treated far less frequently. The present results, noted the scientists, suggest that a long, regular follow up is necessary for patients treated with ranibizumab to obtain and preserve significant visual gain, and not only to achieve visual stabilization.

Source: Cohen SY, Dubois L, Tadayoni R, et al. Results of one-year’s treatment with ranibizumab for exudative age-related macular degeneration in a clinical setting. Am J Ophthalmol 2009;148(3):409-413.

Treatment of Retinal Angiomatous Proliferation with Intravitreal Ranibizumab
In this prospective study of consecutive patients with newly diagnosed or recurrent retinal angiomatous proliferation (RAP) treated with intravitreal ranibizumab at the Jules Gonin Eye Hospital between March 2006 and December 2007, baseline and monthly follow-up visits included best-corrected visual acuity (BCVA), fundus exam and optical coherence tomography. The authors of this study performed fluorescein and indocyanine green angiography at baseline and repeated this at least every 3 months.

They treated 31 eyes of 31 patients (mean age, 82.6 years [SD:4.9]) with 0.5 mg of intravitreal ranibizumab for RAP between March 2006 and December 2007. The mean number of intravitreal injections administered for each patient was 5 (SD: 2.4, range 3 to 12) and the mean follow up was 13.4 months (SD: 3, range 10 to 22). The authors reported that the baseline mean logMAR BCVA was 0.72 (SD: 0.45) (decimal equivalent of 0.2) and that the mean logMAR BCVA was improved significantly (p<0.0001) at the last follow-up to 0.45, SD:0.3 (decimal equivalent 0.35). They also noted that visual acuity (VA) improved by a mean of 2.7 lines (SD 2.5) and that mean baseline central macular thickness (CMT) was 376 µm and decreased significantly to a mean of 224 µm (SD:58). An average of 81.5% of the total visual improvement and 85% of the total CMT reduction occurred during the first post-operative month after one intravitreal injection of ranibizumab and during follow up, an RPE tear occurred in one eye (3.2%) of the study group. No injection complications or systemic drug-related side effects were noted during the follow-up period.

According to the authors of this study, intravitreal ranibizumab injections appeared to be an effective and safe treatment for RAP, resulting in visual gain and reduction in macular thickness. They note that further long-term studies are warranted to evaluate the efficacy of intravitreal ranibizumab.

Source: Konstantinidis L, Mameletzi E, Mantel I, et al. Intravitreal ranibizumab (Lucentis) in the treatment of retinal angiomatous proliferation (RAP). Graefes Arch Clin Exp Ophthalmol 2009;247(9):1165-1171.

Comparison of Imaging Results of the Margins of Geographic Atrophy
Investigators assessed patients with geographic atrophy secondary to dry AMD by means of spectral-domain optical coherence tomography (OCT) as well as fundus autofluorescence (FAF) imaging to study the appearance of margins of geographic atrophy in high-resolution OCT and to correlate those changes with FAF imaging.

They conducted this retrospective, observational case study, in which they examined 23 eyes of 16 patients between 62 and 96 years of age. They analyzed the outer retinal alternations in the junctional zone between normal retina and atrophic retina and correlated them with corresponding FAF and found a significant association between OCT findings and the FAF findings (r=0.67; p<.0001). Severe alterations of the outer retinal layers at margins on spectral-domain OCT correspond significantly to increased autofluorescence; smooth margins on OCT correspond significantly to normal FAF (K, 0.7348; p<.0001).

The investigators of this case study determined that spectral-domain OCT provides in vivo insight into the pathogenesis of geographic atrophy and its progression. Visualization of reactive changes in the retinal pigment epithelial cells at the junctional zone and correlation with increased FAF, secondary to increased lipofuscin, may serve as determinants of progression of geographic atrophy.

Source: Brar M, Kozak I, Cheng Lingyun, et al. Correlation between Spectral-Domain optical coherence tomography and fundus autofluorescence at the margins of geographic atrophy. Am J Ophthalmol 2009;143(3):439-444.

Link Between Retinal Vascular Caliber and Optic Disc and Macular Structure
French researchers conducted this observational cross-sectional study to examine the relationships of retinal vascular caliber with optic disc, macular and retinal nerve fiber layer (RNFL) characteristics as measured with optical coherence tomography (OCT).

The study included a subset of healthy children enrolled in the Singapore Cohort Study of the Risk Factors of Myopia (SCORM) and the researchers measured optic disc, macular and RNFL morphology with Stratus OCT 3. They performed digital retinal photography and measured retinal arteriolar and venular caliber using validated imaging software.

A total of 104 children (mean age 11.51 ± 0.52 years; 50ő male) were included in this study and in multivariate analyses, smaller horizontal integrated rim width and rim area were associated with narrower retinal arterioles and venules (all p<.05), and shorter horizontal rim length was associated with narrower venules (p=.04). According to the researchers, optic disc diameter was not associated with arteriolar or venular caliber. They associated larger vertical cup-to-disc ratios and cup-to-disc-area ratios with narrower venules but not arterioles (p=.01 and p=.003, respectively). Additionally, a thinner average RNFL measurement was associated with narrower arterioles and venules, and smaller total macular volume was associated with narrower venules.

The study researchers concluded that thinner optic disc rims and RNFL measurements were associated with narrower retinal arterioles and venules, and larger cup-to-disc ratios with narrower venules. Their findings suggest that retinal vessel caliber varies systematically with morphologic differences in the optic nerve head, retina and macula.

Source: Lim LS, Saw SM, Cheung N, et al. Relationship of retinal vascular caliber with optic disc and macular structure. Am J Ophthalmol 2009;148(3):368-375.

Details of Iatrogenic Retinal Breaks in 25-Gauge Macular Surgery
The authors of this retrospective, noncomparative, interventional case series sought to describe the incidence and characteristics of iatrogenic retinal breaks in 25-gauge macular surgery. They reported an incidence of retinal breaks that is higher than previously found for 20- or 25-gauge surgery.

The authors included 177 consecutive operations in 171 patients who underwent 25-gauge vitrectomy for idiopathic macular pucker or idiopathic macular hole in this case series. Main outcome measures were the incidence of breaks related to the sclerotomies, the incidence of breaks occurring elsewhere, the incidence of lesions suspicious for traction, the location of identified breaks and intraoperative induction of posterior vitreous detachment (PVD).

Retinal breaks occurred in 15.8% of operations and in 6.2%, breaks were related to the sclerotomies. In 10.7%, breaks were found elsewhere and in 8.5% of eyes, only lesions suspicious for traction were detected. The authors treated breaks or suspicious lesions with external cryocoagulation in a total of 24.3% of cases and identified a statistically significant relation between PVD induction and presence of breaks elsewhere. They found no correlation with lens status, initial diagnosis or preoperative refraction. The authors noted that retinal detachment occurred in 1.7% of cases.

They concluded that, despite the high incidence of breaks, the incidence of postoperative retinal detachment was low. A specific characteristic was the relatively high incidence of breaks elsewhere and their relation to PVD induction. Their findings underscore the importance of scrupulous full 360-degree internal search at the end of each procedure to identify and treat all breaks and suspicious lesions optimally.

Source: Tan HS, Mura M, de Smet MD. Iatrogenic retinal breaks in 25-gauge macular surgery. Am J Ophthalmol 2009;148(3):427-430.