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AMD in Asian Populations

The authors of this study searched published literature reporting age-related macular degeneration (AMD) prevalence in Asian populations to determine the prevalence of AMD in this population compared with the prevalence in white populations.

They limited studies examined to those using standardized grading systems (either the Wisconsin Age-Related Maculopathy Grading System or the International classification proposed by the International ARM Epidemiological Study Group) and used meta-analytical methods to calculate age-specific pooled prevalence of AMD using inverse-variance weighting in a random effect model. Additionally, they calculated pooled estimates of age-standardized prevalence and used a meta-regression model to examine gender differences and differences between Asian and white populations.

The authors identified 9 studies reporting AMD prevalence from 4 Asian populations. They noted that pooled prevalence estimates of early and late AMD in Asian populations aged 40 to 79 years were 6.8% (95% confidence interval [CI], 4.6%–8.9%) and 0.56% (95% CI, 0.30% –0.81%), respectively; corresponding prevalence estimates in white populations were 8.8% (95% CI, 3.8% –13.8%) and 0.59% (95% CI, 0.35% –0.84%), respectively. Reliable prevalence estimates of AMD in Asian persons aged ≥80 years were not available owing to small subject numbers in this age category.

Among persons aged 40 to 79 years, the age-specific prevalence of late AMD in Asians was comparable with that reported from white populations, but early AMD signs were less common among Asians, the authors determined. Further studies in Asian populations are warranted to investigate whether certain specific AMD phenotypes or subtypes, such as polypoidal choroidal vasculopathy, are more common.

Source: Kawasaki R, Yasuda M, Song SJ, et al. The prevalence of age-related macular degeneration in asians: a systematic review and meta-analysis. Ophthalmol 2010;117(5):921-927.

Relationship Between Drusen and Genotypes Associated with AMD

To study associations of small, hard macular drusen and peripheral drusen with genotypes associated with age-related macular degeneration (AMD), investigators in Denmark graded digital grayscale fundus photographs recorded in red-free illumination for the presence of drusen in 1,207 subjects aged 30 to 66 years. They genotyped participants for AMD-related polymorphisms in complement factor H (CFH), in LOC387715 and in complement factor B (CFB).

The investigators reported that the prevalence of 20 or more small, hard macular drusen per eye was 14%, with no association to the investigated polymorphisms. They associated peripheral drusen with CFHY402H (odds ratio [OR], 4.3; 95% confidence interval [95% CI], 1.4–13, for CC versus TT genotypes) as was macular drusen >63 µm (OR, 1.9; 95% CI, 1.1–3.1, for CC versus TT genotypes). Additionally, they associated macular drusen >63 µm with the presence of 20 or more small, hard macular drusen (OR, 1.7; 95% CI, 1.1–2.6) and with peripheral drusen (OR, 2.5; 95% CI, 1.2–5.4).

In this study, the presence of 20 or more small, hard macular drusen per eye was not associated with known AMD-related polymorphisms, whereas the study confirmed an association of peripheral drusen with CFHY402H.

Source: Munch IC, Ek J, Sander B, et al. Small, hard macular drusen and peripheral drusen: Associations with AMD Genotypes in the Inter99 Eye Study. Invest Ophthalmol Vis Sci 2010;51(5):2317-2321.

Affect of Consecutive Intravitreal Bevacizumab Injection on Concentration of Cytokines in AMD

Korean researchers evaluated the changes in aqueous humor cytokine levels following consecutive intravitreal bevacizumab (Avastin, Genentech Inc.) injections in eyes with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD).

They collected aqueous humor samples at the time of intravitreal injection of 1.25 mg of bevacizumab every 7.0 (±2.0) weeks from 10 eyes with AMD for the AMD group and during cataract surgery in nine eyes for the control group. They also measured visual acuity with Early Treatment of Diabetic Retinopathy Study (ETDRS) letters and central macular thickness (CMT) using optical coherence tomography before each injection in the AMD group. The study researchers determined aqueous cytokine levels by immunoassay using multi-analyte biochip array technology (Evidence investigator cytokine and growth factor biochip array, Randox Laboratories Ltd).

They reported that in the AMD group, mean (± standard deviation (SD) aqueous vascular endothelial growth factor (VEGF) levels decreased from 68.0 (± 32.1 pg/ml at baseline to 26.3 (± 19.0 pg/ml after the first injection (p=0.028) and to 25.2 (± 12.8 pg/ml after the second injection (p=0.005). While CMT decreased from 307.7 (± 102.0 µm to 206.8 (± 141.5 µm (p=0.037), the study researchers noted that ETDRS visual acuity increased from 17.6 (± 11.7 letters to 22.0 ± 15.6 letters after three consecutive injections (p=0.017).

They found significantly decreased VEGF levels after the first injection of bevacizumab. These levels were maintained after the second injection, which paralleled the change in visual acuity and CMT.

Source: Roh MI, Lim SJ, Ahn JM, et al. Concentration of cytokines in age-related macular degeneration after consecutive intravitreal bevacizumab injection. Graefes Arch Clin Exp Ophthalmol 2010;248(5):635-640.

Features of Acute CSC vs. Neovascular AMD: A Comparison Using OCT

A retrospective, observational study of 50 eyes with central serous chorioretinopathy (CSC) and 50 eyes with neovascular age-related macular degeneration (AMD) was conducted to compare the optical coherence tomography (OCT) features of acute CSC versus AMD, and to determine if OCT features can distinguish between these two entities.

Stratus OCT line scans (5 mm) were reviewed for presence of subretinal/intraretinal fluid and retinal pigment epithelium detachment and the height of the fluid and detachments were measured using the OCT manual calipers. Additionally, the morphology of the highly reflective line was described.

It was observed that intraretinal fluid (IRF), pigment epithelial detachment (PED), irregularities, thickening and attenuation of the highly reflective line were more often associated with AMD. When present, the PED was significantly greater in AMD than CSC. Patients with CSC were more likely to have subretinal fluid (SRF), and when present, the SRF height was significantly greater in CSC. Moreover, patients CSC also had more hypertrophic outer retinal changes on OCT compared with AMD.

In conclusion, neovascular AMD and acute CSC have distinguishing features on OCT that may help clinicians to differentiate accurately between the two conditions primarily using OCT.

Source: Cho M, Athanikar A, Paccione J, Wald KJ. Optical coherence tomography features of acute central serous chorioretinopathy versus neovascular age-related macular degeneration. Br J Ophthalmol 2010;94(5):597-599.

1-Year Follow Up to Intravitreal Bevacizumab Administered for Idiopathic CNV

Investigators reported the results of 1-year follow-up examinations after intravitreal bevacizumab injection for the treatment of idiopathic choroidal neovascularization (CNV) and found that the injected drug is effective for stabilizing or improving vision in patients with idiopathic CNV.

They intravitreally injected seven eyes in seven patients with idiopathic CNV with 1.25 mg/0.05 mL of bevacizumab and then evaluated the need for retreatment if spectral-domain optical coherence tomography (SD-OCT) showed intraretinal edema or subretinal fluid at the time of a 1-month follow-up exam. The investigators performed fluorescein angiography 1 year after the first injection. Primary outcome measures were best-corrected visual acuity and central foveal thickness using SD-OCT.

The study investigators assessed all 7 eyes at a 1-year follow-up examination. They noted that the mean number of injections per eye was 2.7 and the mean logarithm of the minimum angle of resolution best-corrected visual acuity improved significantly from 0.31 ± 0.29 to 0.15 ± 0.38 (p<0.05). The mean central foveal thickness decreased from 332 ± 83 µm to 261 ± 66 µm (p<0.01). Fluorescein angiography showed no leakage at 1 year in all eyes and all patients whose best-corrected visual acuity improved by ≥ 0.2 logarithm of the minimum angle of resolution had a visual acuity of ≥ 20/40 when first injected at baseline.

This treatment in particular may be well tolerated in patients with a visual acuity of ≥ 20/40 at baseline, the investigators determined; however, additional analyses are needed to assess the long-term safety and the optimal protocol for intravitreal bevacizumab administration.

Source: Inoue M, Kadonosono K, Watanabe Y, et al. Results of 1-year follow-up examinations after intravitreal bevacizumab administration for idiopathic choroidal neovascularization. Retina 2010;30(5):733-738.

Laser-Induced Chorioretinal Venous Anastomosis for CRVO

Australian researchers conducted this prospective, randomized, controlled, multicenter clinical trial to evaluate the effectiveness of a laser-induced chorioretinal venous anastomosis (L-CRA) as a treatment for nonischemic central retinal vein occlusion (CRVO). A total of 113 consecutive patients with a nonischemic CRVO of >3 months' duration and visual acuity of ≤20/50 participated.

According to the researchers, patients were randomized to L-CRA (58 patients) or conventional care (55 patients). They underwent standardized retinal photography, fluorescein angiography and ophthalmic examinations, together with standardized assessments of best-corrected visual acuity, performed by masked visual acuity assessors using Early Treatment Diabetic Retinopathy Study protocols. The researchers performed analysis by intention-to-treat. The primary outcome measure was change in visual acuity at 18 months; secondary outcomes were progression of retinal ischemia and rates of adverse events.

A total of 53 control patients and 55 treatment patients completed the study. The two groups were comparable for age, age- and gender-adjusted mean visual acuity and most other parameters. The study researchers reported that in the treated group of 55 patients, 42 (76.4%) developed an L-CRA. They also noted that over the 18-month follow-up period, treated eyes had an 8.3 letter mean improvement from baseline compared with control eyes (p=0.03). Treated eyes that developed a functional L-CRA achieved an 11.7 letter mean improvement from baseline over the control group after 18 months (p=0.004). Conversion to the ischemic CRVO category occurred in 20.8% of control eyes and in 9.6% of treated eyes overall (p=0.33), the researchers found. Of the treated group who developed an L-CRA where the retinal ischemia was due to progression of the CRVO, 4.9% progressed to the ischemic category (p=0.03). Furthermore, neovascularization developed at the site of the L-CRA in 10 of 55 treated eyes (18.2%) and vitrectomy surgery was required by 5 of 55 treated eyes (9.1%) because of macular traction or nonresolving vitreous hemorrhage.

In conclusion, chorioretinal venous anastomosis was created in 76.4% of eyes with nonischemic CRVO in this study. Eyes that developed an anastomosis had a significant improvement (11.7 letters) in final visual acuity after 18 months, compared with eyes in the control group (p=0.004). Complications were managed successfully with careful follow up and early intervention.

Source: McAllister IL, Gillies ME, Smithies LA, et al. The Central Retinal Vein Bypass Study: a trial of laser-induced chorioretinal venous anastomosis for central retinal vein occlusion. Ophthalmol 2010;117(5):954-965.

Use of Topical Mecamylamine for DME

It has been shown that stimulation of nicotinic acetylcholine (nACh) receptors on vascular endothelial cells promotes angiogenesis and vascular permeability in animal models. This multicenter, phase I/II clinical trial tested the safety and bioactivity of topical mecamylamine, an antagonist of nACh receptors, in patients with diabetic macular edema (DME).

A total of 23 patients with chronic DME received 1% mecamylamine topically twice daily for 12 weeks, the primary end point. Patients underwent safety assessments, measurement of best-corrected visual acuity (BCVA) and measurement of foveal thickness using optical coherence tomography (OCT) at baseline, 1, 4, 8, 12 and 16 weeks.

It was noted that mecamylamine drops were well tolerated and that there were no drug-related safety problems. Mean improvement in BCVA at 1, 4, 8, 12 and 16 weeks was 28, 1.9, 2.4, 0.8 and 3.1 letters, respectively. Little change was observed in mean excess foveal thickness and there was substantial heterogeneity in response, because 8 patients showed convincing improvement in BCVA, foveal thickness or both, 9 patients showed equivocal or no substantial changes and 4 patients showed worsening. Furthermore, 5 patients showed a substantial improvement in BCVA, foveal thickness or both between their last visit while receiving mecamylamine and 1 month after stopping mecamylamine.

This study suggested that administration of topical mecamylamine, a nonspecific nACh receptor blocker, may have heterogeneous effects in patients with DME. Variable expression of nACh receptor subtypes on endothelial cells that have different effects on permeability would provide an explanation for these results and should be investigated, because more specific nACh receptor blockers may dissociate antipermeability and propermeability effects.

Source: Campochiaro PA, Shah SM, Hafiz G, et al. Topical mecamylamine for diabetic macular edema. Am J Ophthalmol 2010;149(5):839-851. DOI: 10.1016/j.ophtha.2010.02.021.

Macular Perfusion in DME Treated with Intravitreal Bevacizumab and Laser Therapy

The following study assessed macular perfusion with fundus fluorescein angiography at the 4-month time point in a prospective randomized, single-center, 2-year trial comparing intravitreal bevacizumab and laser therapy in patients with diabetic macular edema (DME).

All enrolled patients had standard Early Treatment of Diabetic Retinopathy Study (ETDRS) 7-field fundus photographs and fundus fluorescein angiography at baseline and subsequently at 4-month intervals. It was documented that patients were excluded from the study if either the greatest linear dimension of the foveal avascular zone (FAZ) was >1,000 µm in diameter or there was severe perifoveal capillary loss (ETDRS criteria) on fundus fluorescein angiography. The fundus fluorescein angiograms of the bevacizumab (n=42) and laser (n=38) groups were graded for greatest linear dimension of the FAZ, area of the FAZ and perifoveal capillary loss by the Moorfields Reading Centre in a masked fashion.

It was noted that at baseline, the mean greatest linear dimension of the FAZ in the laser group was 685 ± 262 µm and in the bevacizumab group was 737 ± 262 µm. There was no significant difference reported at the 4-month time point (p=0.40) with the mean greatest liner dimension of the FAZ in the laser group recorded as 678 ± 221 µm and in the bevacizumab group was 678 ± 231 µm. The median area of the FAZ in the laser group at baseline was 0.36 mm² (interquartile range, 0.21–0.46) and in the bevacizumab group was 0.33 mm² (interquartile range, 0.27–0.49). No significant difference was noted at the 4-month time point (p=0.30) with the median area of the FAZ in the laser group recorded as 0.35 mm² (interquartile range, 0.20–0.52) and in the bevacizumab group was 0.34 mm² (interquartile range, 0.23–0.47). Similarly, no difference was noted between the two treatment groups (p=0.64) when a comparison was made of the number of grades of change in perifoveal capillary loss observed in each patient. To date, no patients have been withdrawn from the study because of worsening macular ischemia.

No evidence of worsening macular ischemia was observed at 4 months in either group.

Source: Michaelides M, Fraser-Bell S, Hamilton R, et al. Macular perfusion determined by fundus fluorescein angiography at the 4-month time point in a prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT Study): Report 1. Retina 2010;30(5):781-786.

Retinal Blood Flow Velocity and DR

To compare the retinal blood flow velocities of patients with diabetes and healthy control subjects, the authors of this study used a novel device offering a noninvasive diagnostic of retinal function.

They quantitatively analyzed flow velocities in retinal arterioles and venules by retinal function imager scanning in 58 eyes of 42 patients with nonproliferative diabetic retinopathy and 51 eyes of 32 normal subjects. The authors assessed group differences by the mixed-model effect.

They reported that the average velocity in arterial compartments (in mm/s) was 3.74 ± 1.09 for the diabetic group and 4.19 ± 0.99 for the control subjects. The average velocity of all segments, taking associated heart rate and individual segment widths into account, was 17% slower in the diabetic group (p<0.0001). In both groups, the authors noted that average venous compartment velocity was lower than the arterial velocity (2.61 ± 0.65 for the diabetic group; 3.03 ± 0.59 for the control subjects). Moreover, they found that individual vein velocities, taking heart rate and segment widths into account, was 17% slower, on average, in the diabetic group (p<0.0001).

In conclusion, the authors' measurement showed significantly decreased flow velocities in the retinal arterioles and venules of patients with diabetes compared with healthy control subjects, supporting the view of abnormal vessel function in eyes with nonproliferative diabetic retinopathy.

Source: Burgansky-Eliash Z, Nelson DA, Bar-Tal OP, et al. Reduced retinal blood flow velocity in diabetic retinopathy. Retina 2010;30(5):765-773.

Long-Term Visual Outcomes of Acute Retinal Necrosis

Scientists reviewed the medical records of patients with acute retinal necrosis to report the long-term visual outcome. They determined that greater extent of retinitis portends a worse visual prognosis.

A total of 32 patients were diagnosed with acute retinal necrosis from 1998 to 2007 and 20 patients (25 eyes) had at least one follow up and available medical records. It was reported that intravitreal injections of ganciclovir and/or foscarnet were administered in 11 of 25 eyes and that intravenous and oral antiviral medications were used in 14 of 20 and 19 of 20 patients, respectively. Eleven of 25 eyes had <25% of retina affected, 8 of 25 had 25% to 50% of retina affected, and 6 of 25 had >50% of retina affected. The scientists reported that mean visual acuity at all time points was best when retinitis involved <25% and decreased as area increased. All but 1 eye with >50% involvement experienced decreased vision regardless of treatment. Additionally three of 4 eyes with 25% to 50% involvement that received intravitreal antivirals had an improvement in visual acuity of ≥2 Snellen lines and five of 25 eyes developed retinal detachment. None of the six eyes treated with prophylactic laser detached.

According to the study scientists, although intravitreal treatment did not prevent visual acuity loss in patients with severe disease, patients with moderate disease (25–50% retina involved) did well with intravitreal therapy with most having stable or improved visual acuity. Prophylactic laser decreased the rate of detachment.

Source: Meghpara B, Sulkowski G, Kesen MR, et al. Long-term follow-up of acute retinal necrosis. Retina 2010;30(5):795-800.