THE LATEST PUBLISHED RESEARCH

ISIS-DME: Six Months Results
Trends throughout a prospective, randomized, dose-escalation pilot study Intravitreal Steroid Injection Study-Diabetic Macular Edema (ISIS-DME) indicated that a 4-mg intravitreal dose of triamcinolone acetonide may be more effective than a 2-mg dose for treating refractory DME. Also, improvement in vision was more likely in cases of cystoid-type, rather than diffuse, DME. Patients in the study had visual acuity of 20/40 or worse and significant DME that persisted for three or more months after maximal laser treatment.

At three months after a single injection, mean change in visual acuity compared with baseline was 7.1 letters (p=0.01) in the 2-mg group and 12.5 letters in the 4-mg group (p<0.0001). However, there was not a significant difference in visual improvement between the groups (p=0.11). Also at three months, vision improved by more than 15 letters in 23 percent (3/13) of 2-mg group and in 33 percent (5/15) of the 4-mg group (p=0.69). At six months, vision improved by more than 15 letters in 0 percent (0/11) of the 2-mg group and 21 percent (3/14) of the 4-mg group (p=0.23).

Both doses of triamcinolone were well-tolerated. Intraocular pressure rose 10 mmHg or more in 19 percent (3/16) of the 2-mg group and 41 percent (7/17) of the 4-mg group.

Sources: Kim JE, Pollack JS, Miller DG, et al.; ISIS Study Group. ISIS-DME: a prospective, randomized, dose-escalation intravitreal steroid injection study for refractory diabetic macular edema. Retina 2008;28(5):735-740.

Effect of Aspirin Therapy on PDT for CNV
Researchers conducted a retrospective review to explore whether systemic use of aspirin, an inhibitor of platelet aggregation, affects the outcome of photodynamic therapy (PDT) with verteporfin (Visudyne). They reviewed the cases of patients treated with PDT for choroidal neovascularization (CNV) from various causes at one institution between 2001 and 2004. A total of 244 eyes of 222 patients met inclusion criteria, of which 102 eyes of 92 patients were included in the aspirin-taking group.

Patients taking aspirin required more PDT treatments and had worse visual outcomes than patients not taking aspirin. Aspirin takers received an average of 3.11 PDT treatments compared with 2.39 for nonaspirin takers. Decrease in logMAR visual acuity was greater for aspirin takers. A loss of three lines or more occurred in 58 percent of aspirin takers compared with 35 percent of nonaspirin takers. These differences remained statistically significant after controlling for patient age, lesion type and lesion size.

Sources: Ranchod TM, Guercio JR, Ying GS, et al. Effect of aspirin therapy on photodynamic therapy with verteporfin for choroidal neovascularization. Retina 2008;28(5):711-716.

Retinal Characteristics that Precede Geographic Atrophy
To identify specific lesions and the sequence of events that precede geographic atrophy (GA) in eyes with AMD, a group of researchers reviewed the cases of all patients in the Age-Related Eye Disease Study (AREDS) at two clinical centers in whom GA initially appeared in at least one eye at least four years after the baseline study visit. They reviewed pre-GA stereoscopic fundus photographs for all of the patients who met the inclusion criteria (95 eyes of 77 patients). They recorded and graded fundus features at the site of future GA. Three graders reviewed photographs, with independent grading and adjudication by mutual agreement.

Average time from baseline to initial appearance of GA was 6.6 years (4-11 years). The researchers found progression was usually characterized by large drusen formation and development of hyperpigmentation, followed by regression of drusen, appearance of hypopigmentation and ultimately, development of GA. Sometimes, GA was preceded by the appearance of refractile deposits.

Drusen were found in all eyes at the site of later GA. Drusen larger than 125 µm in diameter were found in 96 percent of eyes, confluent drusen in 94 percent, hyperpigmentation in 96 percent, drusen larger than 250 µm in 83 percent, hypopigmentation in 82 percent and refractile deposits in 23 percent. Time from lesion appearance to onset of GA varied by lesion type, ranging from 5.9 years for drusen confluence to 2.5 years for hypopigmentation or refractile deposits.

Source: Klein ML, Ferris FL 3rd, Armstrong J, et al.; AREDS Research Group. Retinal precursors and the development of geographic atrophy in age-related macular degeneration. Ophthalmology 2008;115(6):1026-1031.

Study Results Suggest Gaps in Patient Education about AREDS Supplementation
Based on the results of a cross-sectional clinical case series, more than one-third of AMD patients at a tertiary retinal center who might benefit from AREDS-type supplements were not taking them or taking an incorrect dose. In addition, close to one-fifth of patients who were taking the supplements were not expected to benefit based on their AMD classification.

In the study, patients were surveyed about their supplement use, and the treating ophthalmologist recorded AMD severity using the AREDS classification system. Among the 332 patients surveyed, 93 percent were using supplements; 52 percent of those patients were using an AREDS-like formulation. In the latter group, 80 percent were considered AREDS supplement candidates. Applying AREDS supplementation guidelines to the full cohort, 69 percent were candidates for supplementation. Only 61 percent of these individuals were confirmed to be using the correct formulation and dosage. An additional 6 percent were using the AREDS formulation, but not at the recommended dosage.

Source: Charkoudian LD, Gower EW, Solomon SD, et al. Vitamin usage patterns in the prevention of advanced age-related macular degeneration. Ophthalmology 2008;115(6):1032-1038.

AREDS Supplement Effectiveness Related to CFH Genotype?
The results of a retrospective analysis of patients who participated in AREDS suggest that an individual's response to AREDS-type nutritional supplementation with antioxidants and zinc may be related to complement factor H (CFH) genotype. The main outcome measure of the analysis was the interaction between genetic variants and treatment response as determined by progression from high-risk to advanced AMD.

In 876 white AREDS participants considered to be at risk for progression to advanced AMD (AREDS categories 3 and 4), researchers genotyped for the single nucleotide polymorphisms in the CFH (Y402H, rs1061170) and LOC387715/ARMS2 (A69S, rs10490924) genes. Progression occurred in 264 of the 876 patients from AREDS category 3 to category 4 or 5, or from category 4 to category 5. A treatment interaction was observed between the CFH Y402H genotype and supplementation with antioxidants plus zinc (p=0.03). An interaction (p=0.004) was observed in the AREDS treatment groups taking zinc when compared with the groups taking no zinc, but not in groups taking antioxidants compared with those taking no antioxidants (p=0.59). There were no significant treatment interactions observed with LOC387715/ARMS2.

The authors of the study paper noted that corroboration of their analysis is needed before current patient management is modified.

Source: Klein ML, Francis PJ, Rosner B, et al. CFH and LOC387715/ARMS2 genotypes and treatment with antioxidants and zinc for age-related macular degeneration. Ophthalmology 2008;115(6):1019-1025.

Outcomes of the Veterans Affairs Low Vision Intervention Trial
According to results from the Veterans Affairs Low Vision Intervention Trial (LOVIT), low-vision therapy, including a home visit and assigned homework to encourage practice, is justified for patients with moderate and severe vision loss from macular diseases.

LOVIT was a multicenter, randomized clinical trial conducted from November 2004 to November 2006 with a four-month follow-up. A total of 126 patients were included; 98 percent were white and male. The patients were referred from eye or low-vision clinics and blind rehabilitation centers, had visual acuity in the better-seeing eye worse than 20/100 and better than 20/500, and were eligible for Veterans Affairs services. Interventions included a low-vision examination, counseling, prescription and provision of low-vision devices and six weekly sessions with a low-vision therapist to teach use of assistive devices and adaptive strategies for performing daily living tasks. A group of patients on a waiting list for the program served as controls.

Telephone interviews were performed with the patients in the control group and those who participated in the outpatient low-vision program. Change in visual reading ability and other functioning were estimated from patient responses to the Veterans Affairs Low-Vision Visual Functioning Questionnaire (LV VFQ–48) at baseline and at four months.

The treatment group demonstrated significant improvement in all aspects of visual function compared with the control group. The difference in mean changes was 2.43 logits (95 percent CI, 2.07-2.77, p<.001, effect size 2.51) for visual reading ability; 0.84 logits (95 percent CI, 0.58-1.10, p<.001, effect size 1.14) for mobility; 1.38 logits (95 percent CI, 1.15-1.62, p<.001, effect size 2.03) for visual information processing; 1.51 logits (95 percent CI, 1.22-1.80, p<.001, effect size 1.82) for visual motor skills; and 1.63 logits (95 percent CI, 1.40-1.86, p<.001, effect size 2.51) for overall visual function.

Source: Stelmack JA, Tang XC, Reda DJ, et al.; LOVIT Study Group. Outcomes of the Veterans Affairs Low Vision Intervention Trial (LOVIT). Arch Ophthalmol 2008;126(5):608-617.