THE LATEST PUBLISHED RESEARCH

PDT and High-Dose Intravitreal Triamcinolone for AMD
One-year results of a prospective, comparative, nonrandomized, interventional case series showed that photodynamic therapy (PDT) combined with high-dose intravitreal triamcinolone acetonide (IVTA) improved final best-corrected visual acuity and reduced the need for retreatment in cases of choroidal neovascularization related to age-related macular degeneration.

Thirty consecutive eyes of 30 patients with subfoveal CNV secondary to AMD underwent PDT followed in five days by a 19.4 +/-2.1 mg/0.1 mL triamcinolone injection. Fifteen eyes had no previous treatment (group 1); 15 eyes had previous PDT (group 2); and 15 eyes of 15 patients treated with PDT alone and matched for age and CNV composition and size served as controls. Group 1 improved an average of 0.7 +/-3.7 lines of BCVA (p=0.62) and averaged 1.6 PDT treatments during the 12-month follow-up. Group 2 lost an average of 0.7 +/-1.5 lines (p=0.08) and averaged 1.2 PDT treatments. The control group lost an average of 2.2 +/-0.4 lines (p=0.06) and averaged 2.8 PDT treatments.

Intraocular pressure rose in eight of 14 eyes (57 percent) in group 1 and in seven of 14 eyes (50 percent) in group 2. Four eyes in group 1 and four eyes in group 2 developed cataracts.

Source: Ruiz-Moreno J, Montero JA, Barile S, Zarbin MA. Photodynamic therapy and high-dose intravitreal triamcinolone to treat exudative age-related macular degeneration: 1-year outcome. Retina 2006;26:602-612.

Smoking, Diet and AMD
Two recently published studies assessed the associations between diet and cigarette smoking and AMD. In one of the studies, 2,335 of the 3,654 participants in the Blue Mountains Eye Study (1992 to 1994) were re-examined after five years (1997 to 1999). Dietary data was collected from 2,895 people (79 percent) at baseline to calculate dietary fat intakes. The presence of age-related maculopathy (ARM) was graded from retinal photographs, and logistic regression adjusted for age, sex, vitamin C intake and smoking.

Participants with the highest vs. lowest quintiles of omega-3 polyunsaturated fat intake had lower risk of incident early ARM. A 40-percent reduction of incident early ARM was associated with fish consumption at least once a week, whereas fish consumption at least three times per week appeared to reduce the incidence of late ARM. Investigators found no association between incident ARM and butter, margarine or nut consumption. They concluded that a regular diet high in omega-3 polyunsaturated fat, especially from fish, suggests protection against early and late ARM, but they emphasized that their study could not confirm deleterious effects of higher polyunsaturated fat intakes reported by other clinic-based studies.

Another study, an environmental component of the US Twin Study of Age-Related Macular Degeneration, indicated that cigarette smoking increases the risk of AMD while fish consumption and omega-3 fatty acid intake reduces it. Six hundred eighty-one elderly male twins (222 with AMD and 459 with no maculopathy or early signs) were surveyed for a prior diagnosis of AMD and underwent an eye exam, fundus photography and food frequency and risk factor questionnaires. Logistic regression analyses were used to evaluate risk for AMD according to cigarette smoking and dietary fat intake.

Current smokers had a 1.9-fold increased risk of AMD (p=.06), and past smokers had a 1.7-fold increased risk (p=.009). Higher intake of fish, particularly two or more servings per week, reduced the risk (p=.04). Omega-3 fatty acid intake was inversely associated with AMD comparing the highest and lowest quartile. With higher intake of omega-3 fatty acids, reduced risk of AMD was found mainly among participants with low levels (below median) of linoleic acid intake (p<.001).

Sources: Chua B, Flood V, Rochtchina E, et al. Dietary fatty acids and the 5-year incidence of age-related maculopathy. Arch Ophthalmol 2006;124:981-6. Seddon JM, George S, Rosner B. Cigarette smoking, fish consumption, omega-3 fatty acid intake, and associations with age-related macular degeneration: The US twin study of age-related macular degeneration. Arch Ophthalmol 2006;124:995-1001.

Hormone Therapy and AMD
The University of Michigan’s Department of Epidemiology conducted an ancillary study to the Women’s Health Initiative clinical trial of hormone therapy to determine the effects of conjugated equine estrogens (CEE) or CEE combined with progestin (CEE + P) on AMD. Fundus photography was performed for 4,262 women 65 years and older for the determination of AMD. Participants were recruited from April 2000 to June 2002 at 21 clinical sites an average of five years after randomization. Participants were randomized to treatment with CEE, CEE + P or placebo. All had been treated for an average of five years at the time of ophthalmic evaluation for AMD.

The overall prevalence of any AMD was 21.0 percent. No association was found between CEE + P or CEE alone and early-stage AMD. The CEE + P was associated with a reduced risk of soft drusen after adjustment for covariates and with a reduced risk of neovascular AMD. The investigators concluded that treatment with CEE alone or CEE + P does not affect early- or late-stage AMD.

Source: Haan MN, Klein R, Klein BE, et al. Hormone therapy and age-related macular degeneration: The Women’s Health Initiative Sight Exam Study. Arch Ophthalmol 2006;124:988-92.

tPA for Edema in BRVO
According to a group of researchers in Japan, intravitreal injection of tissue plasminogen activator (tPA) may be an effective treatment for resolving macular edema and improving visual acuity in cases of branch retinal vein occlusion. In a retrospective, interventional case series they treated 17 eyes with macular edema caused by BRVO with 40 k IU tPA. The mean duration of symptoms before treatment had been 3.6 +/-3.8 weeks. Mean logMAR visual acuity improved from a baseline of 0.603 +/-0.327 to 0.388 +/-0.248 at one month (p<.01) and 0.359 +/-0.319 at six months (p<.05). The mean foveal thickness decreased from 738 +/-156 µm at baseline to 454 +/-213 µm at one month (p<.001) and 253 +/-164 µm at six months (p<.001).

Source: Murakami T, Takagi H, Kita M, et al. Intravitreal tissue plasminogen activator to treat macular edema associated with branch retinal vein occlusion. Am J Ophthalmol 2006;142:318-320.

A surgeon performs a transvitreal lamina puncture of the optic disc. (Image courtesy of Donald J. D’Amico, MD.)

Lamina Puncture Unsatisfactory for CRVO
Results of a nonrandomized, consecutive interventional case series indicated that lamina puncture does not restore visual acuity in older patients with central retinal vein occlusion. Twenty patients with an average age of 72, visual acuity of 20/200 or worse, and a mean CRVO duration of 5.4 months (14 nonischemic, 6 ischemic) underwent vitrectomy and lamina puncture of the optic disc. The aim of the puncture, achieved transvitreally, was to create a perivascular opening within the optic nerve head.

Mean preoperative and postoperative visual acuity were the same, in the counting fingers range. Five eyes developed iris neovascularization, and four of those eyes progressed to neovascular glaucoma. The investigators also reported that preoperative ischemia seemed to predispose patients to neovascular complications.

Source: D’Amico DJ, Lit ES, Viola F. Lamina puncture for central retinal vein occlusion: results of a pilot trial. Arch Ophthalmol 2006;124:972-977.

Prevalence of IOP Increase after Intravitreal Triamcinolone
To determine the prevalence of and risk factors for IOP elevation after IVTA, investigators retrospectively reviewed all IVTA cases performed by three vitreoretinal surgeons over a 42-month period beginning in 2000. The review included 570 consecutive eyes of 536 patients who received a single IVTA injection (4 mg/0.1 mL) and a separate group of 43 eyes of 40 patients who received a second injection. Change in IOP was defined as absolute value of IOP elevation (5 mmHg or higher, 10 mmHg or higher) and percentage of baseline (30 percent or higher increase from baseline).

Of the 528 eyes that received single injections, 281 (53.2 percent) had an IOP increase. In 267 eyes (50.6 percent) IOP increased by at least 30 percent; in 245 eyes (45.8 percent) IOP increased by 5 mmHg or more; in 75 eyes (14.2 percent) IOP increased by 10 mmHg or more. Of the 43 eyes that received a second injection, 28 (65.1 percent) had an increase of at least 30 percent of baseline. Five single-injection eyes and one repeat-injection eye required filtering surgery.

Based on their data, the study authors concluded that IOP should be monitored beyond six months after injection. They also wrote that patients with a baseline IOP of more than 16 mmHg and patients receiving a second injection should be carefully monitored.

Source: Rhee DJ, Peck RE, Belmont J, et al. Intraocular pressure alterations following intravitreal triamcinolone acetonide. Br J Ophthalmol 2006;90:999-1003.

International Survey Addresses Safety of Intravitreal Bevacizumab
An article published online by the British Journal of Ophthalmology presented results from the International Intravitreal Bevacizumab (Avastin) Survey. The Internet-based survey was designed to identify adverse events associated with intravitreal bevacizumab therapy for the treatment of neovascular and exudative ocular diseases. Approval for the survey was obtained from the California Pacific Medical Center Institutional Review Board/Ethics Committee. The survey web address was disseminated to the international vitreoretinal community via e-mail, and adverse event rates were calculated from participant responses.

Seventy centers from 12 countries reported on 7,113 injections performed on 5,228 patients with a mean follow-up of 3.5 months. Adverse events reported included corneal abrasion, lens injury, endophthalmitis, retinal detachment, inflammation/uveitis, cataract progression, acute vision loss, central retinal artery occlusion, subretinal hemorrhage, retinal pigment epithelium tears, blood pressure elevation, transient ischemic attack, cerebrovascular accident and death. None of the adverse event rates exceeded 0.21 percent. Systemic adverse events possibly related to bevacizumab included mild blood pressure elevation (n=15, 0.21 percent), transient ischemic attack (n=1, 0.01 percent), cerebrovascular accidents (n=5, 0.07 percent), and deep venous thrombosis (n=1, 0.01 percent). Episodes of elevated systolic blood pressure did not exceed 200 mmHg and were reported as mild.

The authors acknowledged the limitations of the survey: self-reporting of adverse events, varying periods of follow-up, and voluntary responses that did not require a systematic chart review. They also stated that given its limitations, the survey has provided a report of real-world complications, which does not reveal an alarming short-term signal of ocular or systemic adverse events related to use of intravitreal bevacizumab.

Source: Fung AE, Rosenfeld PJ, Reichel E. The international intravitreal bevacizumab safety survey: using the internet to assess drug safety worldwide. Br J Ophthalmol 2006;published online 19 Jul. doi:10.1136/bjo.2006.099598.