ARVO Briefs

Initial Focal Pulsed Laser Treatment Effective for RAP Associated With PED

Treatment of Retinal Angiomatous Proliferation Lesions Associated With Pigment Epithelial Detachment With Focal Pulsed Laser

In a retrospective chart review of consecutive patients, Murphy and colleagues evaluated focal pulsed laser treatment as the primary therapy for inner retinal angiomatous proliferation (RAP) lesions associated with retinal pigment epithelial detachment (PED). Lesions were defined by video indocyanine green angiography (ICG–A) and fluorescein angiography (FA).


Investigators reviewed charts of patients with at least 6 months of follow-up who had RAP lesions associated with PED. Eyes with any choroidal neovascularization (CNV) were excluded. After ICG-A identification and lesion localization, eyes were treated with confluent pulsed 532-nm laser applications using spot sizes of
75 μm to 200 μm. The treatment endpoint was identified as mild inner retinal graying over the RAP lesion.

The study looked at 46 eyes of 41 patients. Of the 41 patients, 85.4% were women, and all five bilateral eyes were in women. The mean age of the study cohort was 80.4 years of age, ranging from 63 to 91 years. The mean baseline visual acuity was 44.3 ETDRS letters or 20/130 on the Snellen chart.

On FA, 67.4% had a pattern of PED only; 26.1% had PED with an occult leakage pattern; and 6.5% had PED with other patterns that mimicked CNV. On ICG-A, the inner retinal lesions were well defined and small, ranging in size from 100 μm to 400 μm.


After treatment, with 80.4% follow-up, there was a mean de-crease compared to baseline of –0.8 ETDRS letters at 3 months, –4.4 ETDRS letters at 6 months and –8.7 ETDRS letters at 12 months. Most eyes had multiple treatments.

At 6 months, the proportion of eyes with stable or improved vision was 79.6%; and at 12 months 67.7% had stable or improved vision. At 6 months, 29 out of 46 (63%) RAP lesions were closed; and at 12 months, 29 out of 37 (78.4%) were closed. At 6 months, 20 out of 46 (43.5%) of PEDs had resolved; and at 12 months, 27 out of 37 PEDs (73%) had resolved. Another 6 out of 37 (16.2%) progressed to fibrovascular scars with no PED.


For RAP associated with PED, investigators found early ICG-A identification and initial focal pulsed laser treatment was a safe, effective treatment for this type of retinal neovascularization. (Note that in this series, RAP could not be diagnosed by FA alone.) Investigators saw little initial adverse treatment effect, with sustained visual benefit for 1 year.

Closing the RAP lesion can be associated with PED resolution, suggesting that leakage from RAP may induce them. These findings suggest that treatment failure may be associated with progression to CNV. Further follow-up to determine long-term visual outcome is warranted.

Study Shows Ties Between Wet AMD and Other Comorbidities
Association Between Neovascular Age-related Macular Degeneration and Incident Myocardial Infarction

Neovascular age-related macular degeneration (AMD) is associated with hypertension, diabetes and a history of myocardial infarction (MI), independent of age, sex and race. This finding comes from a retrospective study of Medicare beneficiaries facilitated by researchers at Penn State University College of Medicine; University of Wisconsin-Madison; and Pfizer Inc.

The analysis also revealed the presence of neovascular AMD is associated with a higher risk of incident MI, independent of demographic factors and comorbidity. The report indicates if these findings are confirmed by other studies with the ability to control for smoking and other lifestyle factors, it may be possible to identify shared common antecedents of AMD and incident MI.


In an effort to investigate the association between neovascular AMD and the development of MI among elderly Americans, researchers reviewed a 5% sample of Medicare beneficiaries and their medical reimbursement claims from 2000 to 2003. A total of 1,519,806 beneficiaries from this sample formed a cohort of subjects who were 65 years of age or older during the 2-year baseline period encompassing 2000 and 2001. The researchers extracted baseline demographic information from the Medicare data, based on relevant ICD-9 codes on at least one claim's "Claim Principal Diagnosis Code" field during this period. Baseline conditions were defined as neovascular AMD, MI, hypertension and diabetes.

After excluding 73,409 prospective subjects with a history of MI at baseline, the team used 2002 and 2003 claims data to identify incident MI cases, which numbered 56,541, among 1,446,397 subjects without a history of MI at baseline.

At baseline, the mean age of this cohort was 76, and it included 60% women and 88% Caucasians. Of this cohort, 11% of the Medicare beneficiaries had been diagnosed with AMD; 19% of that subgroup had the neovascular form of AMD.

Among people with neovascular AMD, baseline age-, sex- and race-adjusted prevalence of hypertension, diabetes and MI were 73%, 28% and 4.7%, respectively. This was in contrast to 65%, 25% and 4.5% among people without neovascular AMD.

After adjusting for age, sex, race, hypertension and diabetes, the 2-year incident odds ratios (and 95% confidence intervals) of MI associated with neovascular AMD were:

• 1.10 (1.00, 1.21) for subjects aged 65 to 69

• 1.11 (1.04, 1.19) for subjects aged 70 to 74

• 1.17 (1.11, 1.23) for subjects aged 75 to 79

• 1.23 (1.18, 1.27) for subjects aged 80 or above.

Study Reveals Rate of 'Real World' Adherence to Preferred Practice Patterns
Evaluation of Adherence to Clinical Practice Guidelines in the Treatment of Age-related Macular Degeneration

Retinal physicians rely on the American Academy of Ophthal-mology's Preferred Practice Pattern (PPP) recommendations about half of the time in their treatment of patients with age-related macular degeneration (AMD). These were the findings of a retrospective study by researchers at the Center for Evidence-Based Medicine at Vanderbilt University Medical Center in Nashville, Tenn.


The PPP guidelines are the most widely accepted set for the treatment of ophthalmic conditions, but until now, there has been little evaluation of the 'real-world' application of its recommendations for AMD, according to Ahmed and colleagues.

In response, the Center for Evidence-Based Medicine designed a study to evaluate adherence to AMD practice guidelines by looking at two questions: How often is Amsler grid testing performed as part of examinations of patients with AMD? And how often is antioxidant supplementation recommended for patients at high risk for development of advanced AMD? According to Dr. Ahmed, these questions were used because "Amsler grid testing and antioxidant and mineral supplementation are given different 'strength of evidence' levels in the PPP."

To answer these questions, researchers randomly selected 107 charts from a retrospective review of all patients diagnosed with AMD seen by three retinal specialists during 2004. "We randomly selected AMD patients seen from January 2004 through December 2004. From that patient mix, we tracked back individual visits from January 2000 through October 2005 to determine whether recommended care was documented or not," Dr. Ahmed said.

The selected visits were reviewed for the following information:

► Diagnosis and severity of AMD by AREDS classification

► Documentation of Amsler grid testing

► Documentation of the recommended use of antioxidant and mineral supplementation.


Researchers reviewed a total of 317 visits. The overall rate of Amsler grid testing was 48%, with no significant difference among the retinal specialists. The overall rate of documented recommended use of antioxidant supplements was 47%.

However, there was a significant statistical difference among the retinal specialists, with one recommending antioxidant supplements to 77% of AMD patients, while another recommended them to 54% of AMD patients and the third recommended them to 20% of AMD patients.

"We found that adherence to both of our benchmarks was similar," Dr. Ahmed said. "This may indicate that strength of evidence does not substantially affect adherence in the treatment of AMD."

Failure to document a verbal recommendation, differences in years of training or lack of knowledge of treatment guidelines are possible explanations for the relatively low rates of PPP adherence, according to Dr. Ahmed. "Further studies are required to see which interventions can improve adherence," he said.

Simple Model Predicts Vitrase Treatment Success
A Simple Predictor of Vitrase Efficacy for BCVA Improvement in Diabetic Patients With Severe Vitreous Hemorrhage

A Simple Predictor of Vitrase Efficacy for Successful Laser Treatment in Diabetic Patients With Severe Vitreous Hemorrhage

A relatively simple measurement of vitreous hemorrhage density — Total Hemorrhage Point Score (THPS) — 1 month post intravitreal injection of lyophilized ovine hyaluronidase for injection (Vitrase), can predict treatment success in diabetic patients, according to two studies.

The predictive model analyses were based on subset analyses of data from the Phase 3 clinical trials of ovine hyaluronidase. In those trials, 1306 patients were enrolled in two randomized, double-masked, placebo-controlled international Phase 3 studies. In both studies, subjects with diabetes who were treated with hyaluronidase had significantly higher success rates than those treated with saline. The present predictive models are based only on subjects with diabetes.


Hyaluronidase treatment for vitreous hemorrhage results in variable clearance rates. Not all patients treated have clearance, so it is valuable to have a predictive model indicating early in the treatment course whether a patient has a significant chance of clearing, according to Abdhish R. Bhavsar, MD, Retina Center, Minneapolis, Minn., a clinical investigator for both studies.

"If a patient receives a hyaluron-idase injection for vitreous hemorrhage, and at 1 month post injection, the hemorrhage has cleared only slightly, we need to decide whether to perform vitrectomy then or to observe the patient for a longer period," Dr. Bhavsar said. "If a patient has a strong chance of not clearing by 3 months post injection, then we would consider vitrectomy as early as 1 month post injection."


Using a scale of 0 to 4 to grade vitreous hemorrhage in the Phase 3 clinical trials, the THPS represents the sum of the hemorrhage density scores in each of the 12 clock hours of the fundus. The predictor is the change in THPS from baseline to month 1 post injection. Using the Receiver Operating Characteristic analysis, the THPS predictor is a relatively strong predictor of whether the hemorrhage will clear sufficiently for successful laser treatment or three-line BCVA improvement.

In one study, THPS helped predict treatment success following a single intravitreous injection of 55 IU or 75 IU hyaluronidase. At 1 month, THPS predicted hyaluronidase treatment success (defined as three or more lines of BCVA gained) at 3 months versus saline injection. At 1 month, THPS also predicted treatment success with hyaluronidase as measured by completion of panretinal laser photocoagulation as defined in the clinical trials by 3 months without vitrectomy when compared to a single injection of saline.