THE LATEST PUBLISHED RESEARCH

Dietary Antioxidants and Incidence of AMD
In an analysis from the Blue Mountains Eye Study, an Australian population-based cohort study, higher dietary intake of lutein and zeaxanthin reduced the risk of long-term incident age-related macular degeneration (AMD). In addition, the analysis showed that higher intake of ß-carotene was associated with an increased risk of AMD and confirmed the Age-Related Eye Disease Study result that zinc is protective against AMD.

Of the 3,654 participants in the study at baseline (1992-1994), 2,454 were re-examined after five years, 10 years or both. Researchers used the Wisconsin Grading System to evaluate stereoscopic retinal photographs and calculated risk ratios (RRs) and 95 percent confidence intervals (CIs) after adjusting for age, gender, smoking and other risk factors. According to the results, participants in the top tertile of lutein and zeaxanthin intake had a reduced risk of incident neovascular AMD (RR 0.35; 95 percent CI 0.13-0.92). Participants with above median intakes had a reduced risk of indistinct soft or reticular drusen (RR 0.66; 95 percent CI 0.48-0.92). Regarding total zinc intake, the RR comparing the top decile with the remaining population was 0.56 for any AMD (95 percent CI 0.32-0.97) and 0.54 for early AMD (95 percent CI 0.30-0.97).

The highest tertile compared with the lowest tertile of total ß-carotene intake predicted incident neovascular AMD (RR 2.68; 95 percent CI 1.03-6.96; p=0.029 for trend). Similarly, ß-carotene intake from diet alone predicted neovascular AMD (RR comparing tertile three with tertile one, RR 2.40; 95 percent CI 0.98–5.91; p=0.027 for trend). This ß-carotene association was evident in both smokers and nonsmokers. Also, higher intake of total vitamin E predicted late AMD (RR compared with the lowest tertile 2.83; 95 percent CI 1.28-6.23; RR for the middle and highest tertiles 2.55; 95 percent CI 1.14-5.70; p=0.22 for trend).

Source: Tan JSL, Wang JJ, Flood V, et al. Dietary antioxidants and the long-term incidence of age-related macular degeneration: The Blue Mountains Eye Study. Ophthalmology 2008;115:334-341.

Study Indicates Interleukin Allele Independently Increases Risk of Wet AMD
Data from a retrospective case-control study suggested that carriers of the interleukin (IL)-8 +781 T allele are at increased risk of developing neovascular AMD, independent of the complement factor H (CFH) Y402H gene polymorphism. Researchers enrolled 312 unrelated Taiwan Chinese patients with late AMD and 180 age- and sex-matched control subjects in the study. They defined late AMD as either atrophic or neovascular. They prepared genomic DNA from peripheral blood from all participants and used polymerase chain reactions to analyze 14 single-nucleotide polymorphisms (SNPs) in candidate genes of five ILs.

Of the 14 SNPs in the five IL genes studied, only the IL-8 +781 C/T SNP was significantly associated with wet AMD (T allele: 46 percent in wet AMD, 28 percent in control subjects, p=1.03 x 10-⁶, odds ratio 2.16, 95 percent CI 1.58-2.94). The association analysis based on genotypes at both IL-8 +781 C/T and CFH Y402H demonstrated that the IL-8 +781 C/T to AMD was not significant when analyzed conditional on the presence of the CFH Y402H C risk allele and vice versa. The IL-8 +781 C/T was in low linkage disequilibrium with CFH Y402H.

Source: Tsai YY, Lin JM, Wan L, et al. Interleukin gene polymorphisms in age-related macular degeneration. Invest Ophthalmol Vis Sci 2008;49:693-698.

Results of PIER Study Published
One-year results of the Phase IIIb PIER Study of ranibizumab (Lucentis) for the treatment of wet AMD were published in the February issue of the American Journal of Ophthalmology. In PIER, 184 patients with predominantly classic, minimally classic or occult with no classic subfoveal choroidal neovascularization were randomized to receive 0.3-mg or 0.5-mg doses of intravitreal ranibizumab or sham injection. Patients received ranibizumab monthly for three months and quarterly thereafter.

The PIER dosing regimen provided significant visual acuity benefit to patients; however, the treatment effect declined in the ranibizumab groups during quarterly dosing. At 12 months, mean change in visual acuity from baseline was -16.3 letters in the sham group, -1.6 letters in the 0.3-mg group, and -0.2 letters in the 0.5-mg group p≤.0001, each ranibizumab dose vs. sham). Visual acuity results from subgroup analyses were consistent with overall results. The incidence of serious ocular or nonocular adverse events was low.

Sources: Regillo CD, Brown DM, Abraham P, et al. Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1. Am J Ophthalmol 2008;145:239-248.

Thermal Laser Treatment Before and after PDT and Triamcinolone for RAP
In a study of 16 consecutive patients, the durability of indocyanine green angiography (ICG)-guided focal thermal laser treatment was better when used as salvage treatment for stage I or II retinal angiomatous proliferation (RAP) lesions following photodynamic therapy and triamcinolone injection than it was when used as initial therapy.

Edema resolved in five of the seven eyes treated initially with focal laser, but lesions recurred in all five of the responders in a mean 4.4 months. In contrast, eight of the nine eyes that received laser treatment after lesion recurrence following prior treatment with PDT and triamcinolone demonstrated initial improvement of edema, and lesions did not recur in four eyes within a year.

This eye from the study received ICG angiography-guided focal thermal laser therapy as primary treatment. (Image courtesy of Scott Cousins, MD)

Source: Bearelly S, Espinosa-Heidmann DG, Cousins SW. The role of dynamic indocyanine green angiography in the diagnosis and treatment of retinal angiomatous proliferation. Br J Ophthalmol 2008;92:191-196.

An Examination of Autofluorescence from the Outer Retina and Subretinal Space
To explore the cause and effect of increased autofluorescence from the outer retina and subretinal space, Richard Spaide, MD, integrated imaging and histopathology information from selected diseases and created a classification scheme. His findings and hypotheses were recently published in the journal Retina.

Dr. Spaide found that diseases that lead to increased autofluorescence from these areas are mainly those that cause separation of the outer retina from the retinal pigment epithelium. The separation, which can arise from increased exudation into the subretinal space or inadequate removal of fluid from the subretinal space, prevents proper phagocytosis of photoreceptor outer segments. Lack of normal outer segment phagocytosis first leads to increased accumulation of outer segments on the outer retina and subretinal space. Diseases that caused such accumulation included acute exudative polymorphous vitelliform maculopathy, vitreomacular traction syndrome, central serous chorioretinopathy, vitelliform macular dystrophy and choroidal tumors.

Over time, the accumulated material appears as an increasingly thick, yellow, autofluorescent coating on the outer retina. Also, atrophy develops with thinning of the deposited material and decreasing autofluorescence. Among Dr. Spaide’s conclusions is that accumulation of the shed but not phagocytized outer segments plays a role in disease manifestations for a number of macular diseases.

Source: Spaide R. Autofluorescence from the outer retina and subretinal space: hypothesis and review. Retina 2008;28:5-35.

Bevacizumab for Refractory Uveitic CME
In a pilot study involving 11 eyes of 10 patients injected since February 2006, intravitreal bevacizumab (Avastin) seemed to be a safe and effective treatment for persistent inflammatory uveitic cystoid macular edema. The physicians who conducted the pilot study defined persistent uveitic CME by optical coherence tomography retinal thickness measurements of greater than 250 µm despite previous treatments. They defined improvement as visual acuity gain of two or more lines and foveal thickness reduction on OCT. The eyes were treated with 1.25 or 2.5 mg of bevacizumab. Median follow-up was 70 days.

Reduction in central retinal thickness was seen as early as two weeks after injection. At four weeks, mean decline in foveal thickness was 127.2 µm. Concurrent improvement in visual acuity was seen in four of 10 patients, and was unchanged in the others. Four patients received two injections, and five patients received three injections. Other than cataract progression in one eye, no ocular or systemic adverse events occurred.

Source: Mackensen F, Heinz C, Becker MD, Heiligenhaus A. Intravitreal bevacizumab (Avastin) as a treatment for refractory macular edema in patients with uveitis: a pilot study. Retina 2008;28:41-45.

Reduced-Exposure PRP Effective while Reducing Pain
Researchers in England performed short-exposure, high-energy laser panretinal photocoagulation on 20 patients with proliferative retinopathy and found it to be as effective as a conventional approach but less painful for patients.

Seventeen of the patients had proliferative diabetic retinopathy, two had ischemic central retinal vein occlusion and one had ocular ischemic syndrome. All were undergoing PRP for the first time. One hemi-retina received treatment with conventional parameters and the other received reduced-exposure treatment. Treatment A (conventional) involved exposure time of 0.1 seconds, power sufficient to produce visible gray-white burns and a spot size of 300 µm. Treatment B (reduced exposure) involved exposure time of 0.02 seconds, a 300-µm spot size and power sufficient to produce visible gray-white burns. Patients were masked to the type of treatments, and the order in which they were carried out was randomized. A 532-nm, frequency doubled Nd:Yag laser used. Patients evaluated pain severity on a visual analogue scale (0=no pain, 10=most severe pain) and were followed for six to 45 months. If additional treatment was required, Treatment B was used.

No evidence of undertreatment was seen during follow-up. Furthermore, all patients preferred Treatment B. Mean pain response to treatment A was 5.11 compared with 1.40 for treatment B (p=0.001).

Source: Al-Hussainy S, Dodson PM, Gibson JM. Pain response and follow-up of patients undergoing panretinal laser photocoagulation with reduced exposure times. Eye 2008;22:96-99.

Rate of Endophthalmitis Following 20-Ga. vs. 25-Ga. PPV
A computerized database search for patients from several U.S. centers who underwent pars plana vitrectomy and were subsequently treated for endophthalmitis revealed that the rate of endophthalmitis after 25-ga. procedures was significantly higher than after 20-ga. procedures. Medical records were reviewed to confirm that the cases of endophthalmitis were associated with PPV and to collect clinical data to meet the study objectives.

During the study period (procedures performed between Jan. 1, 2005 and Dec. 31, 2006) the incidence of endophthalmitis for 20-ga. PPV was two cases per 6,375 (one case per 3,188, 0.03 percent). The incidence for 25-ga. PPV was 11 cases per 1,307 (one case per 119, 0.84 percent, p<0.0001). Of 11 eyes that developed endophthalmitis after a 25-ga. procedure, nine had received postoperative prophylaxis with subconjunctival cefazolin. Endophthalmitis occurred within 15 days of surgery and was usually due to coagulase-negative staphylococci and sensitive to vancomycin. Presenting vision was hand motion or better in all eyes, and final visual outcomes were variable.

Source: Scott IU, Flynn HW, Dev S, et al. Endophthalmitis after 25-gauge and 20-gauge pars plana vitrectomy: Incidence and outcomes. Retina 2008;28:138-142.