New research published Online First in JAMA Ophthalmology suggests that patients with macular edema after retinal vein occlusion who are treated monthly with ranibizumab are more likely to have improvements in reading speed of the affected eyes through six months compared with sham treatment. These results demonstrate that visual acuity improvements translate into measurable improvements in visual function.

There were 789 participants in the two multicenter, double-masked, Phase III clinical trials in which participants with macular edema secondary to branch RVO (BRAVO trial) or central RVO (CRUISE trial) were randomized 1:1:1 to monthly sham (n=132 in BRAVO, 130 in CRUISE), ranibizumab 0.3 mg (n=134 in BRAVO, 132 in CRUISE) or ranibizumab 0.5 mg (n=131 in BRAVO, 130 in CRUISE) for six months. Patients were able to receive macular laser after three months if they met pre-specified criteria. The main study outcome was reading speed, which in the study eye was measured with enlarged text (letter size equivalent to approximately 20/1500 at the test distance) at baseline and one, three and six months. The number of correctly read words per minute was reported. The reading speed test required a sixth-grade reading level and did not account for literacy or cognitive state.

In patients with branch RVO, the mean gain for the 0.5-mg group was 31.3 wpm compared with 15 wpm in sham-treated eyes (difference, 16.3 wpm; p=0.007) at six months. In patients with central RVO, the mean gain for the 0.5-mg group was 20.5 wpm compared with 8.1 wpm in sham-treated eyes (difference, 12.4 wpm; p=0.01) at six months. A gain of 15 or more letters of BCVA letter score corresponded to an increase in reading speed of 12.3 wpm and 15.8 wpm in patients with branch and central RVO, respectively.
JAMA Ophthalmology 2013;():1-6

Suñer I, Bressler N, Varma R, Lee P, et al.

Myocardial Infarction After Treatment with VEGF Inhibitors
Whole-population data suggests that although adverse events are rare, patients treated with VEGF inhibitors are significantly more likely to experience myocardial infarction. It is unknown if this risk is related to the underlying age-related macular degeneration or the use of VEGF inhibitors.

Hospital and death records were examined for 1,267 patients treated with VEGF inhibitors and 399 patients treated with photodynamic therapy attending Western Australia eye clinics from 2002 to 2008, and 1,763 community controls, aged ≥50 years. Hospital records from 1995 to 2009 were analyzed for history of MI, stroke and gastrointestinal bleeding before treatment. Records were searched for evidence of these events in the 12 months after treatment.

The 12-month MI rate was higher for anti-VEGF patients than photodynamic therapy patients and the community group (1.9/100 vs. 0.8 and 0.7). No differences were observed between patients treated with bevacizumab and ranibizumab. The adjusted MI rate was 2.3 times greater than the community (95 percent CI, 1.2-4.5) and photodynamic therapy group (95 percent CI, 0.7-7.7). The 12-month MI risk did not increase with the number of injections administered, nor did stroke and gastrointestinal bleeding differ between any exposure groups.
Retina 2013;33:920-927.
Kemp A, Preen D, Morlet N, Clark F, et al.

LASIK with Next Gen Cyclotorsion Controlled Excimer Laser

New research supports laser-assisted in situ keratomileusis for primary high mixed astigmatism using optimized aspherical profiles and a fast-repetition-rate excimer laser with cyclotorsion control as a safe, effective and predictable procedure.

Fifty-two eyes of 36 patients with primary mixed astigmatism over 3 D underwent LASIK surgery using the sixth-generation excimer laser Amaris with cyclotorsion control and a femtosecond platform for flap creation. Visual, refractive, corneal topographic and aberrometric outcomes were measured during a three-month follow-up. Refractive astigmatic changes were measured by Alpins method.

A reduction of refractive sphere and cylinder was observed three months postop (p=0.001), with an associated improvement of uncorrected distance visual acuity (p=0.001). Best-corrected distance visual acuity remained unchanged in 31 eyes (59.6 percent), while three eyes (5.76 percent) lost two lines of BCDVA. Fourteen eyes (26.9 percent) had spherical equivalent within ±0.5 D of emmetropia and 34 (65.3 percent) had SE within ±1.0 D of emmetropia. Comparing surgically induced and target astigmatism showed no significant difference. A significant induction of higher-order aberration attributable to increase of spherical aberration was found (p=0.003) and seven eyes (13.4 percent) required retreatment.
Am J Ophthalmol 2013;155:829-826.
Alio J, Pachkoria K, Aswad A, Plaza-Puche A.

Anti-VEGF Therapy to Treat Corneal Neovascularization
A systemic review and meta-analysis of literature to evaluate the therapeutic effect of bevacizumab on corneal neovascularization suggests that topical and subconjunctival bevacizumab achieve significant reduction in the area of the neovascularization.

Seven eligible clinical human studies and 18 eligible experimental animal studies were identified through a PubMed search and included in the meta-analysis. The random-effects model (of DerSimonian and Laird) was used to combine the results from selected studies. Heterogeneity was explored using available data and publication bias was assessed.

A significant reduction of corneal NV was seen in clinical human studies, with a pooled reduction of 36 percent overall (95 percent CI, 18 to 54 percent), 32 percent for subconjunctival anti-vascular endothelial growth factor injections (95 percent CI, 10 to 54 percent) and 48 percent for topical treatment (95 percent CI, 32 to 65 percent). Pooled mean change in best-corrected visual acuity showed an improvement in BCVA by 0.04. The summary standardized mean difference in animal studies indicated a statistically significant reduction in the area of corneal NV when treated with bevacizumab compared with the control group by -1.71 (95 percent CI, -2.12 to -1.30). The subtotal pooled standardized mean differences were -1.83 for subconjunctival anti-VEGF injections (95 percent CI, -2.38 to -1.28) and -1.50 for topical treatment (95 percent CI, -1.88 to -1.12).
Cornea 2013;32:535-444.
Papathanassiou M, Theodoropoulou S, Analitis A, Tzonou A, et al.

Additive Risks for Ganglion Cell Dysfunction and Glaucoma
A rat study from University of Melbourne researchers shows that both ω-3 polyunsaturated fatty acid deficiency and repeat acute intraocular pressure cause retinal ganglion cell dysfunction. The combination of these factors results in a cumulative effect that may have implications for glaucoma management. The researchers’ data indicates that sufficient dietary ω-3 PUFA improves RGC, making it less susceptible to IOP insult.

Female Sprague-Dawley rats were fed either ω-3 PUFA sufficient (ω-3+, n=15) or deficient (ω-3-, n=16) diets five weeks before conception, with pups subsequently weaned onto their mothers’ diets. At 20 weeks of age, acute IOP elevation was induced repeatedly through anterior chamber cannulation to 70 mmHg for one hour on three separate occasions, separated by one week. Electro-retinograms were recorded one week after each IOP elevation to assay the photoreceptors (PIN), ON-bipolar cells (PH) and ganglion/amacrine cells (STR).

Researchers say repeat IOP insults result in a specific RGC dysfunction (pSTR -14.5 percent, p=0.035) as does ω-3 deficiency (-26.4 percent, p<0.01). The combination causes a larger RGC functional loss (-40.1 percent, p<0.001) than either does in isolation (p<0.001).
J Glaucoma 2013;22:269-277.
Nguygen C, Vingrys A, Bui, B.

Risks of Bleb-Related Complications in Trabeculectomy
Data collected from a randomized, multicenter clinical trial indicates a low five-year risk of endophthalmitis (1.1 percent) and other bleb-related complications in the trabeculectomy cohort of the Collaborative Initial Glaucoma Treatment Study.

Long-term postoperative complications in the 300 patients randomized to trabeculectomy in the CIGTS were tabulated and Kaplan-Meier analyses were used to estimate the time-related probabilities of blebitis, hypotony and endophthalmitis. After accounting for declining treatment assignment and other early events, 285 patients were included in the final trabeculectomy cohort, and were followed for an average of 7.2 years.

Of the 247 patients with five-plus years of follow-up, 50 required further treatment for glaucoma, 57 required cataract extraction and 40 required bleb revision at least once. Bleb-related complications included bleb leak (n=15), blebitis (n=8) and hypotony (n=4). While 163 patients (57 percent) received 5-fluorouracil during surgery, the occurrences of blebitis, hypotony or endophthalmitis were not significantly associated with its use. The calculated risks of blebitis and hypotony at five years were both 1.5 percent, whereas the risk of endophthalmitis was 1.1 percent.
Am J Ophthalmol 2013;155:174-180.
Zahid S, Musch D, Niziol L and Lichter P.