THE LATEST PUBLISHED RESEARCH

Study Tracks One Year of Bevacizumab Treatment for Wet AMD
At the end of a one-year, prospective, open-label, nonrandomized study, patients with neovascular age-related macular degeneration experienced significant anatomical and functional improvement following treatment with intravitreal bevacizumab (Avastin).

Sixty eyes of 60 patients with subfoveal choroidal neovascularization participated in the study at the American University of Beirut and Hotel Dieu de France Retina Clinics. Included eyes exhibited the presence of subretinal fluid, cystic maculopathy or central retinal thickness greater than 250 µm and CNV less than 5,400 µm in greatest linear dimension. The study included all lesion types except retinal angiomatous proliferation. In an induction phase, eyes were treated with intravitreal bevacizumab (2.5 mg/0.1 mL) at baseline and two additional monthly injections if the macula was not dry. After the induction phase, criteria for re-injection were presence of new fluid in the macula, increased central retinal thickness of at least 100 µm, loss of at least five letters of vision with increased fluid in the macula, new classic CNV or new macular hemorrhages.

Fifty-one patients (51 eyes) completed the 12-month study. Mean best-corrected visual acuity (BCVA) improved from 45.7 letters at baseline to 51.6 letters at the first month (p=.003). Final mean BCVA was 53.1 letters (p=.004), with a mean gain of 7.4 letters compared with baseline. Forty-seven eyes (92.2 percent) lost fewer than 15 letters; 41 eyes (82.4 percent) lost zero letters; 18 eyes (35.3 percent) gained at least 15 letters; and six eyes (11.8 percent) gained at least 30 letters. Mean central retinal thickness decreased from 327.4 µm at baseline to 227.8 µm at 12 months (p<.001). A mean of 3.4 injections were given over the course of the study. No ocular or systemic side-effects occurred.

Source: Bashshur ZF, Haddad ZA, Schakal A, et al. Intravitreal bevacizumab for treatment of neovascular age-related macular degeneration: a one-year prospective study. Am J Ophthalmol 2007;in press.

Bevacizumab Effective for CNV and Large Submacular Hemorrhage
In a retrospective study, treatment with intravitreal bevacizumab led to anatomic improvement and stabilization of visual acuity in eyes with neovascular AMD and large submacular hemorrhage. In the 21 eyes of 19 patients studied, CNV and hemorrhage involved the fovea and comprised more than 50 percent of the total lesion area.

All patients completed at least four months of follow-up, and 12 patients completed 12 months or more. Patients were treated with up to six injections (1 mg/0.04 mL) at a minimum of four-week intervals. At month four, visual acuity improved or stabilized (loss of fewer than three lines) in all eyes. Visual acuity improved by at least three lines in 9.5 percent of eyes. No significant difference could be observed between visual acuity measurements at months four and 12, which suggested that acuity could be maintained during long-term follow-up.

On average, central foveal thickness decreased by 55 µm four weeks after the first injection (p<.001) and by 52 µm at month four (p=.002). Significant anatomic improvement also occurred for maximum retinal thickness, minimum retinal thickness and foveal volume (p<.05) and was maintained during four months of follow-up. Mean size of hemorrhage decreased from 19.7 mm² at baseline to 2.5 mm² at the four-month follow-up (p<.001). The injections were well-tolerated in all patients.

Source: Stifter E, Michels S, Prager F, et al. Intravitreal bevacizumab therapy for neovascular age-related macular degeneration with large submacular hemorrhage. Am J Ophthalmol 2007;144:886-892.

Systemic Bevacizumab for Non-AMD CNV
The results of a nonrandomized, open-label pilot study involving 10 patients provided additional evidence that vascular endothelial growth factor is a critical stimulus for CNV attributable to causes other than AMD. The study, initiated prior to the use of intravitreal bevacizumab, tested infusions of bevacizumab in patients with CNV due to pathologic myopia, birdshot chorioretinopathy, ocular histoplasmosis syndrome, angioid streaks and punctate inner choroidopathy.

Patients were given two infusions of 5 mg/kg two weeks apart followed by re-evaluation at six, eight, 10 and 12 weeks. If leakage persisted at these visits, up to two more infusions two weeks apart were given. Subsequently, patients were followed at 16, 24, 36 and 48 weeks.

At the study’s primary endpoint of 24 weeks, median visual acuity (ETDRS letters read at four meters) improved from 25.5 letters to 48.5 letters, four lines of improvement from baseline (p=.005). Median foveal thickness improved from 346 µm to 248 µm, a 72 percent reduction in excess foveal thickness (p=.007) from baseline. Four patients had complete elimination of leakage on fluorescein angiography; three had near complete elimination; two had modest reduction; and one had no reduction. All patients except one showed a reduction in area of CNV. Median reduction was 43 percent. No patient experienced an elevation of blood pressure or any other complications.

Based on their results, the authors of the study paper suggested that further evaluation of systemic bevacizumab in young patients with CNV may be worthwhile.

Sources: Nguyen QD, Shah SM, Hafiz G, et al. Intravenous bevacizumab causes regression of choroidal neovascularization secondary to diseases other than age-related macular degeneration. Am J Ophthalmol 2007;in press.

Early Bevacizumab for CRVO Produces Surprising Results
Primary, early treatment with intravitreal bevacizumab led to improved visual acuity and fundus appearance for six eyes of five consecutive patients with central retinal vein occlusion (CRVO) in a retrospective, interventional case series. The authors of the study paper noted that their findings are difficult to explain given current theories about CRVO pathophysiology.

The patients did not have other ocular conditions that could have compromised visual acuity. They were treated with bevacizumab within three months of onset of the venous occlusive event and received from four to 10 injections (1.25 mg/0.05 mL) throughout the study. They were followed for a mean of 12 months. Mean logMAR visual acuity at baseline was 20/428, and it improved to 20/53 (p=.035) at last follow-up. The eyes exhibited a statistically significant decrease in macular edema, optic nerve head swelling, venous tortuosity and venous diameter. The largest proportion of change occurred within one month of the first injection. No collateral vessels developed at the optic nerve head.

Source: Ferrara D, Koizumi H, Spaide RF. Early bevacizumab treatment of central retinal vein occlusion. Am J Ophthalmol 2007;144:864-871.

Study Shows Warfarin, Aspirin to be Independent Risk Factors for CRVO
A retrospective case-control study aimed at identifying risk factors for CRVO confirmed the findings of previous studies but also found the use of aspirin and warfarin to be independent risk factors.

Consecutive patients with CRVO examined from July 1, 2005 through July 31, 2006 at a referral practice were compared with a historical gender- and age-matched control group with ocular problems other than vascular occlusive disease from the same practice. Mean age of the 144 CRVO patients was 69.6 years. Postmenopausal estrogen use was more common among women in the control group (p=.029).

Based on univariate analyses, CRVO was associated with hypertension (p<.001), diabetes mellitus (p=.047), glaucoma (p<.001), atrial fibrillation (p=.036) and use of angiotensin-converting enzyme inhibitors (p=.022), aspirin (p<.001) and warfarin (p=.011). Multivariate logistic regression identified the following as independent predictors: glaucoma (adjusted odds ratio [OR], 4.75; p<.001), aspirin use (adjusted OR, 2.66; p=.001) and warfarin use (adjusted OR, 3.34; p=.005).

The authors of the paper noted that the findings suggest the vasculopathic and prothrombotic risks in some patients may not be addressed adequately by antithrombotic therapy, and also that the pathogenesis of CRVO may be more complicated than just the development of a primary thrombus within the vein.

Source: Koizumi H, Ferrara DC, Brue C, Spaide RF. Central retinal vein occlusion case-control study. Am J Ophthalmol 2007;144:858–863.

Results of Second Surgeries for Macular Hole
In a retrospective, single-center case series, reoperating on full-thickness macular holes produced different results depending on whether the holes reopened or were not successfully closed the first time. A second operation on reopened macular holes resulted in 100 percent anatomic closure and significant improvement in vision. However, a second operation for initially unsuccessful surgery resulted in a lower anatomic closure rate (76 percent) and relatively poor final vision even when the holes were successfully closed.

At St. Paul’s Eye Unit in Liverpool, United Kingdom, 532 patients underwent surgery for full-thickness macular hole between March 1995 and March 2005. Fifty-one patients had unclosed holes, and 21 patients had reopened holes after initially successful surgery.

All patients underwent a second pars plana vitrectomy. Internal limiting membrane peeling was performed in some cases. Mean decimal Snellen visual acuity before the second surgery was 0.14 in the reopened group and 0.10 in the unclosed group. Mean visual acuity after the second surgery was 0.42 in the reopened group and 0.19 in the unclosed group.

Source: Valldeperas X, Wong D. Is it worth reoperating on macular holes? Ophthalmology 2008;115:158-163.