This year, research focused on therapy methodology from triple therapy plus to additional off-label usage of bevacizumab. Also, new imaging and monitoring techniques can provide information that may prove useful when creating a care regimen.

 

Triple Therapy

A combination of verteporfin reduced-duration photodynamic therapy, intravitreal dexamethasone and Lucentis (ranibizumab, Genetech), or triple therapy plus, will lessen the total amount of Lucentis required over a nine-month duration in patients with wet age-related macular degeneration (AMD) vs. monthly solo Lucentis treatments, say researchers in Boston.1903/A593 In this randomized clinical trial, 60 patients were placed into one of two treatment groups: monthly Lucentis injections vs. triple therapy plus and a single booster injection of Lucentis one month after therapy.

At nine months, the first group had received nine Lucentis injections, while the second group received an average of 2.6 Lucentis injections and 1.3 sessions of triple therapy plus. Of the patients in group one, 56.7% had no leakage, while 70% of group two demonstrated these same results. Average improvement in visual acuity was 8.6 letters in group one and 12.1 in group two.

Whats the Risk of Choroidal Melanoma? Researchers in Australia and Singapore found that less than 5% of choroidal nevi enlarged more than one-third in an older population over a decade.3734/A577 Drawing on data from the Blue Mountains Eye Study, researchers compared images of choroidal nevi taken at baseline, five and 10 years. Mean nevus diameter in the 145 patients (165 nevi) studied was 1.9 0.9mm at baseline and 2.0 2.5mm at 10 years. Enlargement in surface area was documented in 10 nevi. Most nevi (87%) were slate blue and did not change color over time. No orange pigment or subretinal fluid, which would suggest choroidal melanoma, was observed at any time.

Researchers in Austria and Switzerland also compared the efficacy of triple therapy and Lucentis.5224 Patients were randomized to receive photodynamic therapy (PDT) or sham PDT followed by three monthly Lucentis injections, and after that, on an as-needed basis. At one year, researchers found both equally lessened central retinal thickness. However, the PDT combination therapy resulted in stronger increase in visual acuity9.0 letters vs. 7.5 letters. Researchers note that modified PDT may result in better outcomes, depending on the timing of treatment.

 

Treatment for CSR

Avastin (bevacizumab, Genetech) may benefit patients who have central serous chorioretinopathy (CSR), say researchers in South Bend, Ind.757/D811 Though most patients with CSR will spontaneously improve, some chronic cases will not respond to traditional laser treatment. In this retrospective review, researchers examined the records of 17 patients with chronic CSR. When treated solely with Avastin, all 17 eyes demonstrated a significant reduction in central macular thickness. Visual acuity stabilized or improved in 94% of patients, and most eyes showed reduced or resolved neurosensory detachment after treatment. On average, each eye underwent 3.5 treatments of Avastin until the eye showed clinical resolution on optical coherence tomography, and no cases of endophthalmitis were reported.

Does the thickness of the choroid play a role in glaucoma prevention? Its likely, say researchers in New York.753/D807 Through examination of 291 patients with CSR and 237 age- and gender-matched controls, researchers found that the CSR choroid is significantly thicker than that of a normal patient. In the CSR group, only three patients demonstrated glaucoma compared to 18 patients in the control group. Mean IOP in both groups was not different. So, due to the choroidal blood flow alterations in CSR, patients may be at less risk for glaucoma, the researchers surmise.

PDT may be a successful treatment option for CSR, according to researchers in Norway.751/D805 In this retrospective review, 12 eyes of 12 patients with CSR were examined. Each eye was treated with PDT, and after treatment, demonstrated resolution of subretinal fluid and improvement of visual acuity.

 

MPOD and Imaging

Macular pigment plays a role in protecting the eye from oxidative damage, and there may be a correlation between pigment density and macular degeneration. If pigment can be measured, patients with less can take supplements that will hopefully reduce the risk of AMD.

Researchers in Portland, Ore., compared macular pigment optical density (MPOD) in the fellow eye of patients with unilateral, advanced AMD to eyes in a matched control group and found that the fellow maculae of patients with AMD were not lutein or zeaxanthin deficient.239/A339 Heterochromatic flicker photometry was used to determine the MPOD of AMD patients in the control group. Each participant filled out a dietary survey, and levels of lutein, zeaxanthin, lipoproteins and docosahexaenoic acid were compared. When the two groups were analyzed, the fellow eyes of AMD patients were not deficient, and dietary and plasma macular pigment levels were similar.

Researchers in Salt Lake City and San Diego compared MPOD and noninvasive skin measurement methods. They found that skin measurements are similar for blood values at the baseline visit, but that they dont equate to peak MPOD levels in the retina.729/D783 At this site of the Age-Related Eye Disease Study II (AREDS II), researchers set out to measure tissue levels and distribution of the macular pigments at each visit. Participants MPOD levels were found to be well above the age-adjusted normal range for unsupplemented individualsmore than 70% of enrolled patients were taking lutein or zeaxanthin supplements. Researchers hope this high-risk cohort of patients will provide positive information over five years with and without supplementation.

 

New AMD Imaging Strategies: Improved Understanding Researchers in London examined the potential uses for autofluorescence imaging (AF) in AMD patients and found that it can provide new opportunity for insight into the diseases biological basis.367 This form of molecular imaging allows for the investigation of effects of a specific molecular species associated with the pathology in question. AF targets lipofuscin in the retinal pigment epithelium, and lipofuscin can be a biomarker in AMD, Stargardt disease or other retinal degeneration. Researchers note that AF can detect abnormalities that belie function. Such retinal imaging and functional comparisons may help clinicians monitor and understand localized visual loss, its natural history and the potential benefits of novel treatments, such as genetic or cellular therapy.

The Genetics of AMD

It is now believed that the gene complement factor H (CFH) plays a role in the development of AMD. CFH helps regulate inflammation in the immune system and may be responsible for more than 50% of AMD cases.

One CHF variant that may play a role in AMD is Y40H. Researchers in the ARM Ancillary study from Memphis, Tenn.; Nashville, Tenn.; San Francisco; Boston; and Winston-Salem, N.C., found that this gene variant does not affect the relationship of MPOD, lutein and zeaxanthin.961/D847 Researchers examined a population with early AMD and found that the expected association between AMD and reduced MPOD was non-existent. Therefore, a patient can supplement his or her MPOD regardless of disease status or genetic background.

But, genetic background may predispose a patient to varying levels of success or failure with PDT or anti-VEGF therapy, say researchers in Stanford, Calif.230/A330 They evaluated how the CFH variant Y40H SNP and the A69S SNP of LOC387715 affected the response of wet AMD to treatment with PDT or anti-VEGF therapy. In total, 46 patients underwent anti-VEGF therapy, and 47 underwent PDTeach group included patients of both genetic backgrounds. After anti-VEGF, patients with the CFH variant showed an 11-letter improvement after anti-VEGF, and five-letter improvement after PDT. Those patients with the LOC387715 genotype demonstrated a six-letter improvement after anti-VEGF and five-letter increase after PDT. Also, researchers note that another variant of LOC387715, the risk T allele, actually predisposes a patient to acuity loss.

Another risk factor for AMD: systemic complement activation, according to researchers in Rochester, Minn., and Germany.3520 Proteins in the alternative pathway of complement were measured in plasma for 125 AMD patients and 149 controls. In AMD patients who demonstrated increased systemic activation of the alternative pathway, chronic activation products were significantly elevated. Regulatory protein levels were also elevated. This activation of the alternative pathway of complement correlates with genetic variants in complement genes previously associated with AMD, say researchers.

One CFH variant is associated with an increased likelihood of bilateral involvement in AMD, say researchers in Australia and Cleveland, Ohio.1664 Drawing on data from the Blue Mountains Eye Study and adjusting for age, gender, smoking and white cell count, the CFH CC variant was associated with bilateral soft drusen, retinal pigment abnormalities and bilateral AMD, independent of other risk factors. This genotypes relation with bilateral late AMD, geographic atrophy or neovascular changes, however, could not be confirmed.

 

PHP to Monitor AMD

The Preferential Hyperacuity Perimeter (Foresee PHP, Notal Vision) provides information that supports clinical management of eyes with choroidal neovascularization (CNV), say researchers in Barcelona.954/D840 Researchers compared PHP results to clinical decisions made during the active and post-treatment periods of each patient examined in this retrospective study. Measurements explored included biomicroscopy, fluorescein angiography (FA), visual acuity, OCT and PHP. For 31 eyes, 61 clinical decisions were evaluated. PHP agreed with the decision to extend treatment 79% of the time, 72% of decisions to follow up, 88% of decisions to resume treatment due to reactivation of CNV, and in 82% of cases to follow up again. Researchers note that this information can only support, not replace, clinical decision-making.

Do Patients Adhere to AREDS Recommendations? AREDS published many recommendations regarding vitamin supplement usage among patients with AMD. So, do patients actually follow this regimen? Not typically, say researchers in Hershey, Pa.721/D775 Results of a survey given to 64 patients with AMD indicate that compliance with nutritional supplements, as with glaucoma therapy, is not what one would hope. Only 43% of respondents said they took the suggested dosage of their supplements. Some patients (8%) said that they werent taking supplements due to lack of faith in their benefits, or that they were already taking another multivitamin (8%). Also, 8% of respondents said that their primary doctor advised against its use. Researchers note that these results point to a need for more effective education and general awareness in both the patient population and the medical community.

PHP may also be used to monitor anti-VEGF therapy in cases of AMD, say researchers in Florida and Delaware.246/A346 Of 10 eyes, five were injected with bevacizumab, three with ranibizumab and two with pegaptanib. At one week, PHP found improvement in distortion density in seven eyes, while OCT only saw changes in four. Acuity improvement was only seen in two eyes.

 

Retreatment Assessment: RADICAL

In the PRONTO study, OCT imaging allowed practitioners to evaluate a ranibizumab dosing schedule. Results showed that OCT allowed practitioners to nearly halve the amount of necessary injections. But, as good as OCT is, it may actually miss some patients in which CNV is recurring, say researchers from Tucson, Ariz., who presented interim results of the RADICAL study.5228 Based on OCT and FA, researchers intended to quantify elective re-treatment rates. Within a group of 162 patients, 417 re-treatments took place214 of these were based on OCT criteria alone. The other 203 were based on FA after failing to meet OCT criteria. Researchers concluded that using OCT alone delays or withholds treatment in nearly half of re-treatment decisions, and that the addition of FA to a negative OCT finding during a follow-up regimen doubles re-treatment rates. However, the researchers are still applying this finding to visual outcome.

 

Can a Drop Treat Macular Edema? Yes, say researchers in Puerto Ricothat is, if the drop is nepafenac.1349/A88 In this small study, authors monitored macular thickness and acuity in 13 eyes that had macular edema due either to diabetes or retinal vascular occlusions. Patients treated with nepafenac 0.1% t.i.d. were followed for one year at three-month intervals. At three months, acuity improved by an average of three lines in 77% of eyes. At six and 12 months, acuity remained unchanged or improved slightly. Eyes with diabetic macular edema improved an average of five lines, and eyes with vascular occlusions showed average improvement of two lines. At 12 months, macular thickness was improved by an average of 208m258m in diabetic eyes and 37m in eyes with occlusions. Researchers note that further research is necessary to understand nepafenacs mechanism of efficacy.

Avastins Other Uses

Intravitreal bevacizumab effectively treats macular edema due to branch retinal vein occlusion (BRVO), say researchers in Japan.3719/A562 Researchers reviewed the eyes of 47 patients treated with bevacizumab for macular edema due to BRVO. After 12 months of follow up, CRT decreased from 525m to 271m, and improvement in visual acuity was seen in 29 eyes49% demonstrated a final acuity of 20/40 or better. No ocular toxicity or adverse effect was noted during or after treatment.

Researchers in Boston used intravitreal bevacizumab to treat macular telangiectasis type 2 (MacTel 2).756/D810 Six eyes were injected with bevacizumab to treat macular edema caused by MacTel 2, with a mean follow-up time of eight months. Of the six, four demonstrated improved acuity, one remained unchanged, and one patients acuity decreased. So, though further study is needed, this off-label use of bevacizumab may benefit MacTel 2 patients, researchers say.

For the text of each abstract, referenced here by presentation number, please go to www.arvo.org.