U.S. Release of New Vitreoretinal Forceps Bausch & Lomb Storz Ophthalmic Instruments has announced the U.S. release of a new single-use endgripping forceps for vitreoretinal surgery. HR Centralis Expands Volk's Offerings Volk Optical has expanded its laser therapy lens offerings with the HR Centralis, providing detailed views of the central retina and posterior pole.

Intravitreal Bevacizumab Plus Intravitreal Triamcinolone for RVO

In this retrospective, consecutive case series, investigators reported 6 months of results of combined treatment of intravitreal bevacizumab and triamcinolone in patients with retinal vein occlusion (RVO).

They injected intravitreal bevacizumab (1.25 mg) combined with intravitreal triamcinolone (2 mg) into 16 patients with RVO (eight with branch retinal vein occlusion [BRVO] and eight with central retinal vein occlusion) and reviewed patients' charts for age, sex, previous ocular interventions, duration of follow up, number of intraocular injections, intraocular pressure (IOP) and central macular thickness measured by optical coherence tomography (OCT). Only patients who completed 6 months of follow up were included.

According to the investigators, mean age and number of injections were 72.9 ± 11.99 years, and 2 ± 0.81, respectively. In eight patients with CRVO, initial visual acuity was logMAR 1.09 ± 0.67 and mean visual acuity at 1, 3 and 6 months was logMAR 0.98 ± 0.55 (p=0.59), 1.33 ± 1.05 (p=0.4) and 1.4 ± 1.2 (p=0.34) respectively. In eight patients with BRVO, initial visual acuity was logMAR 1.025 ± 0.58 and mean visual acuity at 1, 3 and 6 months was 0.56 ± 0.21 (p=0.05), 0.61 ± 0.17 (p=0.03) and 0.66 ± 0.34 (p=0.12) respectively. Moreover, mean initial central macular thickness for the whole group was 527 ± 182 µm and mean central macular thickness at 6 months was 379 ± 156 µm (p<0.001).

This study suggests that combined treatment with intravitreal bevacizumab and intravitreal triamcinolone improves structural outcome in patients with retinal vein occlusion. The combination of triamcinolone acetonide and bevacizumab offered no advantage over previously published results with intravitreal bevacizumab injections alone for improving vision at 6 months.

Source: Ehrlich R, Ciulla TA, Moss AM, Harris A. Combined treatment of intravitreal bevacizumab and intravitreal triamcinolone in patients with retinal vein occlusion: 6 months of follow-up. Graefes Arch Clin Exp Ophthalmol 2009; Nov 8 [Epub ahead of print]. DOI: 10.1007/s00417-009-1211-6.

Retinal Sensitivity and Morphology During Antiangiogenic Treatment of RVO

This Austrian study evaluated the association between functional and anatomic retinal changes during anti-vascular endothelial growth factor (VEGF) therapy with bevacizumab (Avastin) in patients with cystoid macular edema secondary to retinal vein occlusion (RVO) using microperimetry and spectral domain optical coherence tomography (SD-OCT).

A total of 28 patients with cystoid macular edema secondary to RVO participated in this prospective, uncontrolled study. The patients initially received 3 consecutive intravitreal injections of 1.25 mg bevacizumab at 4-week intervals. Further treatment was based on morphologic (OCT) and functional best-corrected visual acuity (BCVA) findings and during the 1-year follow up, a rigorous standardized evaluation was performed monthly. Macular function was documented by microperimetry and BCVA based on the Early Treatment in Diabetic Retinopathy Study (ETDRS). Morphologic parameters included central retinal thickness (CRT) as measured by conventional OCT, and central subfield thickness (CST), mean retinal thickness (MRT) and retinal volume (RV) measured by SD-OCT. Additionally, imaging of retinal morphology using OCT and SD-OCT and evaluation of retinal function assessed with microperimetry and ETDRS charts during 12-months of anti-VEGF treatment served as the main outcome measures.

It was reported that within 6 months, the mean area of absolute scotoma was reduced from 21.4% of the central visual field to 6.4% and remained at this level until month 12 (7.4%). Mean BCVA improved from 51 to 66 letters on ETDRS charts. Additionally, the CRT, CST and MRT decreased significantly (p<0.002) and remained stable during the follow up. The RV values did not improve significantly under therapy and furthermore, statistical analysis using a linear effects model revealed significant associations between the functional and morphologic outcome, most notably between BCVA, macular sensitivity, CRT, CST and MRT values.

Central retinal morphology, especially CRT and CST measured by conventional and SD-OCT, and retinal function improved significantly during treatment of RVO with a flexible dosing regimen of intravitreal bevacizumab. It was determined that functional (central visual acuity and visual field) and morphologic parameters (retinal thickness) were significantly related. These associations highlight the value of OCT imaging for assessing this disease entity.

Source: Kriechbaum K, Prager F, Geitzenauer W, et al. Association of retinal sensitivity and morphology during antiangiogenic treatment of retinal vein occlusion over one year. Ophthalmology 2009;116(12):2415-2421.

Outcome of OCT-Guided Bevacizumab Treatment of Macular Edema Due to RVO

German researchers evaluated the long-term outcome of an OCT-guided reinjection scheme for bevacizumab treatment of macular edema (ME) due to retinal vein occlusion (RVO) and found that patients with RVO benefit from treatment with bevacizumab.

Patients with persistent ME (>250µm) due to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) received intravitreal bevacizumab 2.5 mg/0.1 mg and the researchers performed visual acuity (ETDRS), ophthalmic examination and OCT at baseline and at 6- to 8-week intervals. They performed reinjections only if OCT showed persistent or recurrent ME.

A total of 61 patients with a minimum follow up of 25 weeks were included in this analysis and mean follow up was 60 ± 29 weeks. In CRVO patients, central retinal thickness (CRT) decreased from 748 ± 265 µm to 372 – 224 µm (p<0.001) and visual acuity (VA) improved by 1.9 ± 3.2 lines. The researchers noted that in BRVO patients, mean CRT decreased from 601 ± 206 µm to 386 ± 178 µm (p<0.001) and VA improved by 1.8 ± 2.6 lines. Additionally, 33% of CRVO and 15% of BRVO patients did not show a ME recurrence for ≥25 weeks at last visit. Thirty-seven percent of CRVO and 50% of BRVO patients suffered recurrences of ME within the last 25 weeks, whereas 30% of CRVO and 35% of BRVO patients did not achieve a complete resolution of ME at any follow-up visit after receiving a minimum of three injections. According to the study researchers, CRVO patients with dry interval of ≥25 weeks at last visit were significantly younger, had a thinner CRT at baseline and more often had a complete resolution of ME after the first injection. Furthermore, in CRVO and BRVO, final VA was correlated significantly with initial VA, patients' age and final CRT and change of VA was correlated with change of CRT in BRVO.

Favorable long-term results without necessity of further injections were achieved in 33% and 15% of CRVO and BRVO patients, respectively. The researchers reported that the remaining patients needed repeated injections to treat ME recurrences. One-third of the CRVO/BRVO patients did not improve VA and further injections might be discontinued in these patients.

Source: Hoeh AE, Ach T, Schaal KB, et al. Long-term follow-up of OCT-guided bevacizumab treatment of macular edema due to retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 2009;247(12):1635-1641.

Dose Comparison of Intravitreal Bevacizumab as Primary Treatment for Macular Edema Secondary to BRVO

The investigators in this study compared the injection burden, central macular thickness (CMT) and change in best-corrected visual acuity (BCVA) after injecting 1.25 mg or 2.5 mg of bevacizumab as needed in patients with primary macular edema secondary to branch retinal vein occlusion (BRVO).

They conducted an interventional, retrospective, comparative multicenter study of 63 eyes with macular edema secondary to BRVO that were treated primarily with intravitreal bevacizumab (38 eyes, 1.25 mg; 25 eyes, 2.5 mg). The main outcome measures were the CMT and the change of BCVA at 24 months.

The investigators noted that all patients completed at least 24 months of follow up and that the mean number of injections per eye was 3.6 in the 1.25-mg group and 4.3 in the 2.5-mg group (p=0.4770). At 24 months, in the 1.25-mg group, the logarithm of the minimum angle of resolution BCVA improved from baseline 0.38 ± 0.63 (p<0.0001) units to 0.64 ± 0.6 units for the 2.5-mg group (p<0.0001). In the 1.25-mg group, 26 (68%) eyes gained ≥ 3 of Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity and 2 (5%) eyes lost ≥ 3 lines of ETDRS visual acuity, according to the investigators. They reported that the CMT in the 1.25-mg group improved from 453 ± 140 µm (p<0.0001) versus 444 ± 175 µm to 234 ± 80 µm in the 2.5-mg group (p<0.0001). They saw no cases of endophthalmitis and reported no systemic adverse events.

In conclusion, intravitreal bevacizumab at doses up to 2.5 mg seems to be effective in improving BCVA and reducing CMT in macular edema secondary to BRVO. The study investigators found no statistically significant differences between the two dose groups with regard to the number of injections, CMT and change in BCVA.

Source: Wu L, Arevalo JF, Berrocal MH, et al. Comparison of two doses of intravitreal bevacizumab as primary treatment for macular edema secondary to branch retinal vein occlusions: results of the Pan American Collaborative Retina Study Group at 24 months. Retina 2009;29(10):1396-1403.

Impact of Female HRT and Oral Contraceptive Use with AMD

The authors of this study investigated whether female reproductive history and hormone replacement therapy (HRT) or birth control pills (BCP) influence risk for age-related macular degeneration (AMD) and whether genetic factors interact with HRT to modulate AMD risk.

They examined related and unrelated female participants (n=799) using generalized estimating equations adjusting for age and smoking and considered individuals with AMD grades 1-2 “unaffected” (n=239) and those with grades 3-5 “affected” (n=560).

When comparing all cases to controls, significant inverse associations were observed for HRT (Odds Ratio [OR=0.65, 95% CI 0.48–0.90, p=0.008] and BCP [OR=0.60, 95% CI 0.36–0.10, p=0.048].) When the authors were stratified by AMD severity (early vs. geographic atrophy vs. neovascular), they noted that the inverse association remained significant (HRT OR = 0.45, 95% CI 0.30–0.66, p<0.0001; BCP OR = 0.55, 95% CI 0.32–0.96, p=0.036) only when comparing neovascular AMD to controls. To determine whether HRT or BCP modified the effect of established genetic risk factors, the authors examined all pairwise HRT-genotype and BCP-genotype interactions. They also observed the strongest interactions for HRT x ARMS2 coding SNP (R73H) rs10490923 (p=0.007) and HRT x ARMS2 intronic SNP rs17623531 (p=0.019).

The study authors believe that their findings provide the first evidence suggesting that ARMS2 interacts with HRT to modulate AMD risk and are consistent with previous reports demonstrating a protective relationship between exogenous estrogen use and neovascular AMD. These results highlight the genetic and environmental complexity of the etiologic architecture of AMD; however, further replication is necessary to validate these findings.

Source: Velez DR, Gallins P, Polk M, et al. Inverse association of female hormone replacement therapy and oral contraceptive use with age-related macular degeneration and interactions with ARMS2 polymorphisms. Invest Ophthalmol Vis Sci 2009;Nov 20 [Epub ahead of print]. DOI: 10.1167/iovs.09-4000.

Outcomes of Treating AMD with Bevacizumab vs. Ranibizumab

To report early outcomes of a prospective, double-masked, controlled trial comparing bevacizumab to ranibizumab for the treatment of age-related macular degeneration (AMD), this single-center study randomized patients who met inclusion criteria 2:1 to bevacizumab or ranibizumab. Each patient contributed one eye to the study and all subjects and investigators (except for the pharmacist responsible for study assignments) were masked to treatment arms. Additionally, visual acuity (VA) was checked on Early Treatment Diabetic Retinopathy Study (ETDRS) chart and patients were given either bevacizumab or ranibizumab every month for the first 3 months, followed by optical coherence tomography-guided, variable-dosing schedule. Main outcomes measured were VA and foveal thickness.

A total of 20 patients completed the 6-month follow up (13 patients received bevacizumab and 7 received ranibizumab). It was reported that no subjects in either group lost more than 15 letters on ETDRS charge; the average preoperative VA was 31.6 letters in the bevacizumab groups and 30.4 letters in the ranibizumab group. At 6 months follow up, mean vision was 46.4 letters in the bevacizumab group and 37.4 letters in the ranibizumab group. Two-tailed ttest failed to show statistical significance between the two groups. Furthermore, patients in the bevacizumab group underwent an average of 5 injections, while patients in the ranibizumab group underwent a mean of 4 injections.

In conclusion, early results of a head-to-head, randomized, double-masked, prospective, single-center controlled trial between bevacizumab and ranibizumab show no difference in efficacy between the two treatments for choroidal neovascularization in the treatment of AMD. As this study conveys results of a small number of patients, further studies with larger sample sizes are needed to establish statistical significance.

Source: Subramanian ML, Ness S, Abedi G, et al. Bevacizumab vs ranibizumab for age-related macular degeneration: early results of a prospective double-masked, randomized clinical trial. Am J Ophthalmol 2009;148(6):875-882.

AMD and Levels of Lead and Cadmium in Retinal Tissues

Researchers conducted this laboratory investigation to measure lead and cadmium in retinal tissues of human donor eyes with and without age-related macular degeneration (AMD).

They determined lead and cadmium concentrations in retinal tissues (neural retina and retinal pigment epithelium [RPE]-choroid complex) in 25 subjects with AMD (50 donor eyes) and 36 normal subjects (72 donor eyes) using inductively coupled plasma-mass spectrometry. They also graded severity of AMD using color fundus photographs and the Minnesota Grading System. Differences in metal concentrations were compared using Wilcoxon rank-sum tests.

According to the researchers, the neural retinas of subjects with AMD had increased lead concentrations (median, 12.0 ng/g; 25% to 75% interquartile range, 8 to 18 ng/g; n=25) compared with normal subjects (median, 8.0 ng/g; 25% to 75% interquartile range, 0 to 11 ng/g; p=.04; n=36). Additionally, they reported no difference in lead concentration in the RPE-choroid complex between subjects with AMD (median, 198 ng/g; 25% to 75% interquartile range, 87 to 381 ng/g) and normal subjects (median, 172 ng/g; 25% to 75% interquartile range, 100 to 288 ng/g; p=.25). Cadmium concentration in the neural retina (median, 0.9 µg/g; 25% to 75% interquartile range, 0.7 to 1.8 µg/g) and RPE-choroid complex (median, 2.2 µg/g; 25% to 75% interquartile range, 1.8 to 3.7 µg/g) in subjects with AMD was not different from concentrations in the neural retina (median, 0.9 µg/g; 25% to 75% interquartile range, 0.7 to 1.4 µg/g; p=.32) and RPE-choroid complex (median, 1.5 µg/g; 25% to 75% interquartile range, 0.9 to 2.5 µg/g; p=.12) of normal subjects.

The study researchers concluded that AMD is associated with excess lead in the neural retina, and that this relationship suggests that metal homeostasis in AMD eyes is different from that of normal eyes.

Source: Erie JC, Good JA, Butz JA. Excess lead in the neural retina in age-related macular degeneration. Am J Ophthalmol 2009;148(6):890-894.

Safety and Efficacy of Intravitreal Ranibizumab for Nonsubfoveal Choroidal Neovascularization Secondary to AMD

The following retrospective, multicentric, noncomparative, interventional case series assessed the efficacy and safety in the treatment of nonsubfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD) with intravitreal ranibizumab.

Included were patients with naïve extrafoveal and juxtafoveal choroidal neovascularization treated with intravitreal ranibizumab and a follow up of 1 year. Patients were evaluated using visual acuity testing with Snellen charts, fluorescein angiography and optical coherence tomography scans.

Of 15 patients with a mean age of 72.4 years (SD, 7.2), there were 11 juxtafoveal lesions (73.3%) and 4 extrafoveal lesions (26.6%). It was noted that 8 lesions were predominantly classic (53.3%), 6 were occult (40%) and 1 was minimally classic (6.6%). The mean visual acuity improved from 20/60 (mean logarithm of the minimum angle of resolution = 0.47) at baseline to 20/40 (mean logarithm of the minimum angle of resolution = 0.34) at the 1-year follow-up visit (p=0.03) and the mean foveal thickness improved from 312 µm to 262 µm (p=0.01). Additionally, the mean lesion size (disk areas) improved from 1.9 to 1.1 (p=0.01). No cases progressed to a subfoveal location. It was reported that the mean number of injection was 3.8 and as far as complications, there was an endophthalmitis and a macular hole.

In this study, intravitreal ranibizumab showed efficacy for the treatment of nonsubfoveal choroidal neovascularization secondary to AMD, mainly in terms of preventing subfoveal progression.

Source: Arias L, Ruiz-Moreno JM, Gómez-Ulla F, et al. A 1-year retrospective review of ranibizumab for naive nonsubfoveal choroidal neovascularization secondary to age-related macular degeneration. Retina 2009;29(10):1444-1449.

Characteristics of a New Macular Dystrophy

The authors of this study sought to clinically phenotype an inherited macular dystrophy with peculiar intraretinal pigment spots, cysts and hemorrhage in a 24-year-old female proband and her family.

They performed dilated fundus examination, optical coherence tomography and, in select cases, fluorescein angiography and electroretinography on extended family members of the proband. In total, they examined 17 family members, representing 3 generations and ranging in age from 5 to 64 years. The authors reported that visual acuities ranged from 20/20 to 20/200 and that amblyopia and strabismus were frequently present in affected individuals. Consistent with an autosomal dominant pattern of inheritance, 7 family members had multiple central macular cystic spaces and flat, round, densely pigmented spots within the retina. The study authors also noted right-angle vessels and telangiectasis in the central macula. Furthermore, two subjects showed evidence of active macular neovascularization with leakage on fluorescein angiography at ages 7 and 24 years, which was responsive to either focal laser or a single injection of bevacizumab. In those cases examined, multifocal elecroretinography showed a diminished foveal response.

According to the authors, the spotted cystic neovascular macular dystrophy appears to represent a new autosomal dominant retinal condition. Because these patients are at risk for choroidal neovascularization, identification of the responsible gene may provide insight into the mechanisms of pathological neovascularization.

Source: Mahajan VB, Russell ST, Stone EM. A new macular dystrophy with anomalous vascular development, pigment spots, cystic spaces, and neovascularization. Arch Ophthalmol 2009;127(11):1449-1457.

Enhanced Depth OCT Imaging of the Choroids in Central Serous Chorioretinopathy

Investigators evaluated the choroidal thickness in patients with central serous chorioretinopathy and found that enhanced depth imaging spectral-domain optical coherence tomography (SD-OCT) demonstrated a very thick choroids in patients with central serous chorioretinopathy.

On patients with central serous chorioretinopathy, they conducted enhanced depth imaging SD-OCT, which they obtained by positioning a SD-OCT device close enough to the eye to acquire an inverted image. They obtained seven sections, each comprising 100 averaged scans, within a 5° - 30° rectangle to encompass the macula. The subfoveal choroidal thickness was measured from the outer border of the retinal pigment epithelium to the inner scleral border.

The mean age of subjects undergoing enhanced depth imaging SD-OCT, as reported by the investigators, was 59.3 years (standard deviation, 15.8 years). Of the 19 patients, 17 (89.5%) were men and 12 (63.2%) of the 19 had bilateral clinical disease. The choroidal thickness measured in 28 eligible eyes of the 19 patients was 505 µm (standard deviation, 124 µm), which was significantly greater than the choroidal thickness in normal eyes (p≤0.001).

Their findings provide additional evidence that central serous chorioretinopathy may be caused by increased hydrostatic pressure in the choroids.

Source: Imamura Y, Fujiwara T, Margolis R, Spaide RF. Enhanced depth imaging optical coherence tomography of the choroids in central serous chorioretinopathy. Retina 2009;29(10):1469-1473.

Role of PI3K/AKT Pathway in Development of Retinoblastoma

Israeli researchers analyzed AKT1mutations in retinoblastoma to gain insights into the role PI3K-AKT pathway plays in the development of this tumor.

They analyzed 24 samples of retinoblastoma from children for mutations in the AKT1, PTEN AND K-RAS genes, using a chip-based matrix-assisted laser desorption-time-of-flight (MALDI-TOF) mass spectrometer. They also analyzed mutations in the PIK3CA gene in 16 retinoblastoma samples using direct sequencing.

According to the researchers, these results show that the mutation E17K/AKT1 was not detected in the 24 samples of retinoblastoma analyzed. They identified K-RAS mutations in two samples but noted no mutations in any of the other genes analyzed by a mass array system. On direct sequencing of 16 samples for the P1K3CA gene, one sample showed gain of function mutation in exon 9; in another sample, a genetic polymorphism of unknown significance (rs17849079) was detected in exon 20.

The study researchers determined that although the PI3K-AKT pathway is known to be dysregulated in retinoblastoma, the low frequency of oncogenic mutations in the AKT1, PIK3CA and PTEN genes suggests a different activating mechanism.

Source: Cohen Y, Merhavi-Shoham E, Avraham-Lubin BC, et al. PI3K/Akt pathway mutations in retinoblastoma. Invest Ophthalmol Vis Sci 2009;50(11):5054-5056.

Oral Transmucosal Fentanyl Citrate as an Analgesic Agent in Retinal Photocoagulation

This prospective, randomized, double-masked crossover study evaluated the analgesic effect of 200 µg oral transmucosal fentanyl citrate during peripheral retinal scatter photocoagulation to determine the side effect profile.

A total of 35 consecutive patients undergoing peripheral retinal scatter photocoagulation were randomized into 2 groups. Each group attended twice, 1 week apart and received a standardized laser treatment at each visit. Group 1 received 200 µg oral transmucosal fentanyl citrate at Visit 1 and placebo at Visit 2, whereas Group 2 received the lozenges in reverse order. After each visit, each patient completed a 100-mm visual analog scale pain score and rating scale regarding systemic side effects.

It was reported that the mean visual analog scale for patients receiving placebo was 36.4 (SD, 31.5) and that the mean visual analog scale for patients receiving 200 µg oral transmucosal fentanyl citrate was 19.2 (SD, 20.5) (p=0.0014). Overall, 4 patients (11%) reported moderate or severe adverse systemic side effects and no clinically significant changes in systemic observations or adverse events occurred.

Oral transmucosal fentanyl citrate at a dosage of 200 µg is an effective and convenient analgesic for use in peripheral retinal scatter photocoagulation, it was determined. This agent was found to be well tolerated in the outpatient setting; however, a larger study would be necessary to ascertain safety across a larger population of opiate-naïve patients.

Source: Hillier RJ, Aboud A, Thind G, et al. Oral transmucosal fentanyl citrate: a novel analgesic agent for use in retinal photocoagulation. Retina 2009;29(10):1506-1512.