David R. Guyer

Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease

Aptamers are oligonucleotide ligands that are selected for high-affinity binding to molecular targets. Pegaptanib sodium (Macugen; Eyetech Pharmaceuticals/Pfizer) is an RNA aptamer directed against vascular endothelial growth factor (VEGF)-165, the VEGF isoform primarily responsible for pathological ocular neovascularization and vascular permeability. After nearly a decade of preclinical development to optimize and characterize its biological effects, pegaptanib was shown in clinical trials to be effective in treating choroidal neovascularization associated with age-related macular degeneration. Pegaptanib therefore has the notable distinction of being the first aptamer therapeutic approved for use in humans, paving the way for future aptamer applications.

Digital indocyanine green videoangiography and choroidal neovascularization.

This report describes a new system for digital indocyanine green videoangiography (ICGV) that provides enhanced imaging of the choroidal circulation. This newly assembled system was used to study a consecutive series of 129 patients with exudative age-related macular degeneration (AMD), and ill-defined or occult choroidal neovascularization (CNV). Overall, 39% of the patients in this study with occult CNV could be reclassified as having well-delineated or so-called classic CNV by virtue of the additional findings provided by ICGV. In this series, ICGV was particularly useful in identifying occult CNV in eyes with a large, serous pigment epithelial detachment (PED) and in eyes with recurrent CNV after previous laser photocoagulation treatment. Some of these patients were selected for laser photocoagulation of the abnormal choroidal vessels in order to evaluate the feasibility of this form of treatment on the basis of combined clinical, fluorescein angiographic, and ICGV findings. The results of this study suggest that ICGV is an important adjunct in the evaluation, classification, and laser treatment of patients with occult CNV secondary to AMD.

Indocyanine green videoangiography of older patients with central serous chorioretinopathy.

Purpose: The authors studied the indocyanine green (ICG) videoangiography findings of central serous chorioretinopathy (CSC) in older adults. Background: Central serous chorioretinopathy in older adults may be confused with the exudative forms of age-related macular degeneration (AMD) because the two entities may have similar ophthalmoscopic and fluorescein angiographic findings. Because of its enhanced ability to image the choroidal circulation, ICG videoangiography has been used to describe certain choroidal vascular abnormalities in young adults with CSC, as well as older patients with choroidal neovascularization (CNV). The ICG videoangiography findings in CSC in older adults is largely unknown. Methods: The authors performed ICG videoangiography on 36 patients aged 50 years or older with CSC to characterize their findings. Results: The ICG videoangiography findings of the patients were consistent, revealing choroidal vascular hyperpermeability manifested by areas of hyperfluorescence that were first seen in the midphase of the angiogram. In the later phases of the angiogram, there were dispersion of the hyperfluorescence and a distinctive silhouetting of the larger choroidal vessels. Conclusions: Older patients with CSC have a unique temporal and topographic pattern of hyperpermeability that can help establish the proper diagnosis.

Central Serous Chorioretinopathy in Younger and Older Adults

PURPOSE The purpose of the study is to investigate the demographic characteristics and clinical findings of central serous chorioretinopathy (CSC). METHODS This study examined a consecutive series of 130 patients with CSC seen over an 18-month period. RESULTS The mean age of the patients when examined was 51 years, and the male-to-female ratio was 2.6:1.0. A total of 62 patients were older than 50 years of age when first examined. Although the patients shared some clinical and angiographic similarities, the older patients had a lower mean visual acuity and were more likely to have diffuse retinal pigment epitheliopathy, bilateral involvement, and secondary choroidal neovascularization than were the younger patients. With ophthalmoscopic and angiographic examination results, it was possible to differentiate CSC in older adults from choroidal neovascularization. CONCLUSION This study expands the clinical concept of CSC. The male-to-female ratio was much lower, and the range of ages of the patients was much greater than in previous studies. Disease manifestations in older adults differed somewhat from those seen in younger adults. In older patients, CSC can be distinguished from other exudative maculopathies, particularly that of choroidal neovascularization secondary to age-related macular degeneration.

Systemic findings associated with central serous chorioretinopathy.

PURPOSE To determine systemic factors associated with central serous chorioretinopathy. METHODS In a retrospective study, 230 consecutive patients with central serous chorioretinopathy examined in a referral setting were compared with a historical gender-matched and age-matched control group of 230 patients with ocular findings who were examined in the same referral setting. RESULTS The median age of the patients was 49.8 years, and of the control subjects, 50.0 years. The male-female ratio for both groups was 2.7:1. Patients with central serous chorioretinopathy were more likely to use psychopharmacologic medications (odds ratio = 2.6; 95% confidence interval = 1.30 to 5.19; P = .0049) and corticosteroids (odds ratio = 3.17; 95% confidence interval = 1.30 to 7.70; P = .0067) and were more likely to have hypertension (odds ratio = 2.25; 95% confidence interval = 1.39 to 3.63; P = .0008) than were the control subjects. CONCLUSIONS This study identified psychopharmacologic medication use, corticosteroid use, and hypertension as factors associated with central serous chorioretinopathy. These findings reinforce the concept that stress and adaptations to stress play a role in this disorder. The findings of possible associations between central serous chorioretinopathy and both hypertension and corticosteroid usage suggest that these modifiable factors may influence morbidity of central serous chorioretinopathy.

Digital Indocyanine-green Angilography in Chorioretinal Disorders

The authors performed digital indocyanine-green angiography in 37 patients with chorioretinal disorders. Eighteen patients had choroidal neovascularization, 7 patients had atrophic age-related maculopathy, and 12 patients had uncommon choroidal and retinal disorders. A Topcon indocyanine-green camera was integrated with a digital (1024-line resolution) angiography system. Compared with conventional video or photographic indocyanine-green angiography, this technique offers enhanced image resolution, the possibility of direct qualitative comparison with fluorescein angiography, image archiving, hard-copy generation, and tracing capabilities to plan laser treatment strategies and monitor the adequacy of laser therapy after surgery.

Retinal choroidal anastomoses and occult choroidal neovascularization in age-related macular degeneration.

OBJECTIVE This study was designed to identify the incidence of retinal choroidal anastomoses in patients with occult choroidal neovascularization (CNV) and focal hot spots on indocyanine green (ICG) angiography, to identify the clinical and angiographic features that would assist in their identification, and to determine if the presence of these anastomotic lesions affect the outcome of laser therapy. DESIGN Combined prospective and retrospective cross-sectional study. PARTICIPANTS One hundred fifty consecutive patients with newly diagnosed occult CNV secondary to exudative age-related macular degeneration and focal hot spots on ICG angiography were evaluated prospectively. In addition, a retrospective review was performed on 79 eyes previously reported to have undergone laser photocoagulation treatment with ICG guidance. METHODS AND TESTING: In all cases, stereo color and red-free photographs, and stereo fluorescein and digital ICG angiograms were obtained for evaluation. MAIN OUTCOME MEASURES Images obtained by all four techniques were evaluated for the presence of a retinal choroidal anastomosis. Associated clinical and angiographic findings were noted. In the retrospective review, the success rate of laser treatment was correlated with the presence or absence of a retinal choroidal anastomosis. RESULTS Of the 150 eyes evaluated prospectively, 31 (21%) were found to have a retinal choroidal anastomosis. Retinal choroidal anastomoses were found in 27% of patients with associated serous pigment epithelial detachment (PED), whereas 13% were found in those without an associated elevation of the retinal pigment epithelium. Seventy-one percent of eyes had multiple anastomotic connections. Ninety percent of eyes had at least one retinal vein involved in the anastomotic connection. Clinical evidence of preretinal and intraretinal hemorrhage and cystic edema coupled with angiographic evidence of intraretinal dye leakage were key features of retinal choroidal anastomoses. In the retrospective review, seven patients were found to have retinal choroidal anastomoses with associated serous PED and demonstrated a very low (14%) success rate for laser treatment. CONCLUSIONS Retinal choroidal anastomoses can present as a primary manifestation of the exudative process in age-related macular degeneration. They may be seen in eyes with and without detachment of the retinal pigment epithelium. Specific clinical and angiographic features have been identified that can aid in the diagnosis of these vascular anomalies. Their presence represents a poor prognostic sign for successful ICG-guided laser treatment.

Polypoidal choroidal vasculopathy masquerading as central serous chorioretinopathy

OBJECTIVE To differentiate polypoidal choroidal vasculopathy (PCV) from central serous chorioretinopathy (CSC). DESIGN A retrospective, observational case series. PARTICIPANTS Thirteen patients originally diagnosed with CSC proved to have PCV after more extensive evaluation and follow-up. METHODS A clinical and angiographic review of patients with manifestations of CSC, including macular detachment. MAIN OUTCOME MEASURES Demographic data, funduscopic examination, and fluorescein and indocyanine green (ICG) angiographic findings. RESULTS Thirteen patients initially suspected of having CSC were ultimately diagnosed as having PCV. These eyes had exudative macular detachments secondary to a small caliber, polypoidal choroidal vascular abnormality or so-called polypoidal choroidal neovascularization. The clinical manifestations in the fundus varied. They included multiple, variably sized serous pigment epithelial detachments, neurosensory retinal detachment, lipid deposition, patchy atrophy of the pigment epithelium and indistinct staining from decompensation of the posterior blood-retinal barrier on fluorescein angiography. In reality, the suspected PEDs proved to be polypoidal lesions of PCV when imaged with ICG angiography. CONCLUSIONS The clinical diagnosis of CSC or PCV generally poses little challenge to the experienced retinal specialist. However, in CSC with persistent and/or recurrent exudation, a myriad of retinal pigment epithelial changes may evolve that make it difficult to differentiate these two entities. In such patients, ICG angiography is useful in differentiating CSC from PCV. An accurate clinical diagnosis is important since each of these entities, CSC and PCV, may differ in terms of their risk factors, natural course, and visual prognosis.

Indocyanine-green angiography.

&NA; Indocyanine‐green angiography represents a major advance in imaging of the choroidal circulation. Recent technical innovations have permitted this diagnostic technique to find clinical application in many chorioretinal conditions. The indocyanine‐green molecule has proven to be safe for human study. In age‐related macular degeneration, indocyanine‐green angiography may play an important role in the diagnosis of patients with occult choroidal neovascularization, leading to eventual increased efficacy with laser photocoagulation treatment. Histopathologic confirmation of a lesion noted by ICG angiography has been made. In multiple inflammatory conditions, as well as with central serous chorioretinopathy, distinct ICG patterns have emerged that may facilitate better understanding of the disease processes. With greater experience, ICG angiography may provide improved imaging, a better understanding of the pathogenesis, and new treatment approaches for various chorioretinal conditions.

External beam radiation therapy for choroidal neovascularization

OBJECTIVE This study aimed to determine the effect of external beam radiation therapy on choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN The study design was a nonrandomized clinical trial with an historic control group. PARTICIPANTS A total of 91 patients were treated with external beam radiation. These patients were compared retrospectively to the 119 patients in a control group. INTERVENTION Patients with subfoveal CNV who did not meet the criteria for laser treatment defined by published reports from the Macular Photocoagulation Study Group or who did not want laser treatment were considered for radiation therapy in a nonrandomized, prospective clinical trial. Additional entry criteria for this prospective study included visual acuity better than or equal to 20/320 on the Early Treatment Diabetic Retinopathy Study chart and a lesion size less than 12 disc areas. The patients were treated with 5 fractions of 200 cGy 6 MV external beam photons. MAIN OUTCOME MEASURES The visual acuity measured at baseline was compared to the visual acuity after 1 year of follow-up. RESULTS The mean baseline visual acuity of the 91 patients entered into the Radiation Study was 20/80. After 1 year, 83 patients (91.2%) completed follow-up, and their mean visual acuity dropped to 20/200. By comparison, the mean baseline visual acuity of the control patients also was 20/80, and after 1 year, the control subjects had a mean visual acuity of 20/125. At 1 year of follow-up, 49.4% of patients treated with radiation and 38.1% of the control subjects lost 3 or more lines of visual acuity (P = 0.16). CONCLUSIONS This study found that external beam radiation using 1000 cGy in 5 fractions, a dose similar to that used in previous studies, was not effective in the treatment of CNV secondary to AMD. These results suggest that patients should not be treated with this dose of external beam radiation for CNV secondary to AMD.