Faculty Bibliography

OBJECTIVE: Recent studies have shown that indocyanine-green videoangiography (ICG-V) is useful to image occult choroidal neovascularization. The authors studied the ICG-V findings in fellow drusen eyes of patients with unilateral exudative age-related macular degeneration (AMD). The authors also studied the occurrence of exudative changes to determine whether ICG-V is useful in predicting future exudative changes in these eyes with only drusen. DESIGN: Cohort study. PARTICIPANTS: The authors studied 432 consecutive patients diagnosed with unilateral exudative AMD in whom the fellow eye had only drusen by clinical fundus examination and fluorescein angiography. All of these eyes had ICG-V performed. Follow-up data were obtained in all eyes with abnormal indocyanine-green (ICG) angiograms and randomly sampled ICG angiograms of normal eyes. MAIN OUTCOME MEASURES: The initial ICG findings were classified as showing normal or abnormal hyperfluorescence. Abnormal hyperfluorescence eyes were subdivided into focal spots (focal areas of hyperfluorescence < 1 disc area in size) and plaques (areas of hyperfluorescence > 1 disc area). The development of exudative changes in eyes with normal and abnormal hyperfluorescence was compared. RESULTS: Of the 432 fellow eyes, 386 (89%) eyes with drusen had a normal ICG-V study, whereas 46 (10 focal spots and 36 plaques) (11%) eyes had an abnormal ICG-V. Exudative changes occurred in 6 (10%) of 58 normal ICG eyes and 9 (24%) of 38 eyes with abnormal ICG findings during a mean follow-up period of 21.7 months. The difference between drusen eyes with normal ICG angiograms and those with plaques on ICG-V regarding future exudative changes (10% vs. 27%, respectively) was statistically significant (P = 0.038). CONCLUSIONS: Abnormal ICG findings were found in 11% of eyes with clinically and fluorescein angiographically nonsuspicious drusen. The subgroup of patients with plaques on ICG-V had a higher chance of having exudative changes develop. Indocyanine-green videoangiography may be a predictive indicator of future exudative changes in eyes with drusen. A much larger prospective study seems justified

OBJECTIVE: The authors evaluated the clinical, fluorescein, and indocyanine green (ICG) angiographic characteristics of the macular variant of idiopathic polypoidal choroidal vasculopathy (IPCV). DESIGN: Observational case series. PARTICIPANTS: The records, photographs, and fluorescein and ICG angiograms of eight eyes of seven patients with IPCV lesions confined to the macula were reviewed. MAIN OUTCOME MEASURES: The visual acuity, fundus examination, fluorescein and ICG angiographic characteristics, and clinical course were compared. RESULTS: All patients demonstrated polypoidal lesions arising from macular choroidal vessels on ICG angiography. One patient had bilateral lesions. These lesions appeared hyperfluorescent in the early phases of both fluorescein and ICG angiography. Late-phase leakage was seen in cases associated with subretinal fluid or exudate. None of these patients demonstrated polypoidal lesions arising from the peripapillary choroidal circulation or peripapillary choroidal neovascularization. Three eyes with polypoidal lesions that were associated with subretinal fluid and exudates were treated with photocoagulation. Five eyes were not treated. Final visual acuity ranged from 20/20 to hand motions. Severe visual loss was associated with vitreous and subretinal hemorrhage, but this resolved without permanent severe visual loss in several cases. CONCLUSIONS: In the macular variant of IPCV, ICG and fluorescein angiography demonstrate characteristic macular polypoidal lesions without evidence of peripapillary lesions. The vascular origin of these polypoidal lesions appears to be the macular choroidal circulation. This is distinguished from classic IPCV, in which lesions appear to arise from the peripapillary choroidal circulation. Visual prognosis appears to be good, with most patients retaining visual acuity of 20/80 or better. If subretinal fluid or exudates reduce visual acuity, photocoagulation should be considered

OBJECTIVE: This study aimed to histologically localize indocyanine green (ICG) dye in the geriatric primate and human eye and to correlate these findings with clinical ICG angiography. DESIGN: The study design was a clinicopathologic correlation. PARTICIPANTS: Six eyes of three geriatric monkeys (Maccaca mulatta) with macular drusen, 19 to 29 years of age, housed at the California Primate Research Center and an enucleated human eye from a 66-year-old patient with choroidal melanoma were examined. INTERVENTION: All six monkey eyes and the human eye underwent clinical ICG angiography. Five monkey eyes were enucleated at varying intervals after intravenous ICG dye injection for histologic examination. One monkey eye was removed without prior ICG injection as an age-matched control. The human eye was enucleated after intravenous injection of ICG dye. MAIN OUTCOME MEASURES: Infrared fluorescence microscopy of freeze-dried tissue sections was performed to detect ICG fluorescence. Histologic sections were stimulated with an 810-nm diode laser, and the fluorescence emitted was detected with a Hamamatsu infrared camera. The images were digitally recorded. The distribution of fluorescence on histologic examination was correlated with the fluorescence of the clinical ICG angiogram. RESULTS: Infrared fluorescence microscopy of monkey sections localized fluorescence within retinal and choroidal vessels early after injection of ICG dye. The ICG fluorescence was seen in the extravascular choroidal stroma within 10 minutes after injection. The stromal fluorescence persisted in sections obtained 50 minutes after injection of ICG. The retinal pigment epithelium (RPE)-Bruch's membrane complex was brightly fluorescent in the middle- and late-stage histologic sections. Drusen deposits were brightly fluorescent at all timepoints examined. Similar findings were observed in freeze-dried tissue sections of the human eye. The fluorescence detected on histologic sections correlated closely with the fluorescence of the clinical ICG angiograms for the same interval. CONCLUSIONS: The ICG dye does not remain solely within the choroidal intravascular space but extravasates into the choroidal stroma and accumulates within the RPE. Extravascular ICG binds to drusen material. These findings will enhance the interpretation of clinical ICG angiography

Age-related macular degeneration, the leading cause of legal blindness in people over age 60 worldwide, represents a public health crisis that deserves the attention and understanding of all physicians. The dry form of the disease is more common than the wet, but the wet form causes the most severe vision loss. Other than vision aids (e.g., glasses, magnifiers), no treatments or preventive measures are currently available for patients with dry macular degeneration, and laser photocoagulation with fluorescein angiography is the only clinically proven therapy for neovascular disease. Indocyanine green angiography is a promising new imaging tool that may improve detection of patients likely to benefit from laser therapy. Until better diagnostic and treatment options are available, early screening and patient education offer the best hope for reducing the widespread devastation caused by this disease

OBJECTIVE: Possible risk factors for hemiretinal vein occlusion were identified and compared with risk factor profiles for central and branch retinal vein occlusion. DESIGN: The design was a multicenter case-control study. METHODS: The authors identified 79 patients with hemiretinal vein occlusion (HRVO), 258 patients with central retinal vein occlusion (CRVO), 270 patients with branch retinal vein occlusion (BRVO), and 1142 control subjects at 5 clinical centers. Risk factor data were obtained through interviews, clinical examinations, and laboratory analyses of blood specimens. RESULTS: Systemic hypertension and history of diabetes mellitus were associated with increased risk of HRVO. Risk of CRVO increased with history of diabetes, systemic hypertension, and higher erythrocyte sedimentation rate (females only); risk of CRVO decreased with increasing amounts of physical activity and increasing amounts of alcohol consumption. Systemic hypertension, higher body mass index, and higher alpha2-globulin levels were associated with increased risk of BRVO, whereas higher high-density lipoprotein levels and increasing levels of alcohol consumption were associated with decreased risk of BRVO. Glaucoma history was associated with all three types of retinal vein occlusion. CONCLUSION: Patients presenting with retinal vein occlusion should be evaluated for cardiovascular disease, diabetes, and glaucoma

OBJECTIVE: This study aimed to use a new technique for ocular imaging, digital subtraction indocyanine green angiography (DS-ICGA), to evaluate patients with occult choroidal neovascularization (CNV). DESIGN: The design was a cross-sectional study of patients with occult CNV. PARTICIPANTS: A total of 31 eyes of 31 patients were studied. INTERVENTION: Digital subtraction of sequentially acquired indocyanine green angiographic frames was used to image the progression of the dye front in eyes with occult CNV. A method of pseudocolor imaging of the choroid was developed that allows differentiation and identification of underlying choroidal arteries and veins. RESULTS: The DS-ICGA of occult CNV showed consistent findings. Occult CNV was imaged with greater detail and in a shorter period of time than with conventional indocyanine green angiography. The fundus landmarks were retained with DS-ICGA much better than with conventional indocyanine green angiography. CONCLUSIONS: The DS-ICGA uses time to dissect the choroidal circulation. With DS-ICGA, occult CNV could be imaged more quickly and in greater detail than with conventional imaging techniques. The DS-ICGA may improve the authors ability to image, and subsequently treat, occult CNV

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