K. Bailey Freund

Intravitreal bevacizumab (Avastin) treatment of macular edema in central retinal vein occlusion: a short-term study.

Purpose: To report the short term anatomic and visual acuity response after intravitreal injection of bevacizumab (Avastin, Genentech) in patients with macular edema due to central retinal vein occlusion (CRVO). Methods: The authors conducted a retrospective study of patients with macular edema due to CRVO who were treated with at least one intravitreal injection of bevacizumab 1.25 mg in 0.05 mL. Patients underwent Snellen visual acuity testing, optical coherence tomography (OCT) imaging, and ophthalmoscopic examination at baseline and follow-up visits. Results: There were 16 eyes of 15 consecutive patients with a mean age of 76.1 years (SD 9.8 years). Intravitreal triamcinolone had been previously administered to 9 patients, but all of these patients either had no improvement or had excessive intraocular pressure caused by the triamcinolone. The patients received a mean of 2.8 injections of bevacizumab per eye. No adverse events were observed, including endophthalmitis, clinically evident inflammation, increased intraocular pressure, retinal tears, retinal detachment, or thromboembolic events in any patient. The mean central macular thickness at baseline was 887 &mgr;m and decreased to a mean of 372 &mgr;m at month 1 (P < 0.001). The mean baseline acuity was 20/600 (logMAR = 1.48) and the mean acuity at month 1 was 20/200 (logMAR = 1.05), a difference that was highly significant (P = 0.001). At last follow-up, a mean of 3 months after the first injection, the mean visual acuity was 20/138 (logMAR = 0.84), which was significantly better than baseline (P < 0.001). Visual acuity improvement, defined as a halving of the visual angle, was seen in 14 of the 16 eyes. Conclusion: Initial treatment results of patients with macular edema secondary to CRVO did not reveal any short-term safety concerns. Intravitreal bevacizumab resulted in a significant decrease in macular edema and improvement in visual acuity. The number of patients in this pilot study was limited and the follow-up is too short to make any specific treatment recommendations, but the favorable short-term results suggest further study is needed.

Age-related Macular Degeneration and Choroidal Neovascularization

The neovascular variant of age-related macular degeneration is amenable to laser photocoagulation treatment within well-defined guidelines established by clinical trials. However, only a limited number of patients meet eligibility criteria for this form of treatment, principally because of the ill-defined, or occult nature, of the choroidal neovascularization commonly seen. Previous studies have estimated that one half of patients with neovascular age-related macular degeneration have occult neovascularization at initial manifestation of the disease. We examined the initial findings of 67 patients with newly diagnosed unilateral neovascular age-related macular degeneration. Eighty-seven percent of these patients (58 of 67) had disease that did not meet Macular Photocoagulation Study Group guidelines for laser photocoagulation treatment. As so few patients are eligible for laser photocoagulation, further research into new techniques of diagnosis and treatment for this disorder is warranted.

Corticosteroids and central serous chorioretinopathy

PURPOSE The purpose of this study is to investigate the relationship between corticosteroid use and central serous chorioretinopathy (CSC). DESIGN A prospective, case-controlled study. PARTICIPANTS AND CONTROLS A consecutive series of patients with acute manifestations of CSC and a control group matched for age, race, and gender were recruited between January 2000 and July 2000. METHODS A detailed clinical history was taken, and fundus examination with slit-lamp biomicroscopy was performed on all patients. Fluorescein angiography was obtained on the study patients. RESULTS A total of 50 patients was recruited. Twenty-six patients (52%) had a history of exogenous steroid use, including oral, intravenous, intranasal, and intraarticular administration. Two additional patients had a history of endogenous hypercortisolism (Cushings syndrome). In a matched control group, eight patients (18%) had a history of steroid use. The difference in corticosteroid exposure between study patients and controls was statistically significant (P < 0.0001). MAIN OUTCOME MEASURES History of corticosteroid use or Cushings syndrome. CONCLUSIONS This study is consistent with previous reports associating steroid use with CSC. It identifies corticosteroids as a significant risk factor for the development of acute, exudative macular manifestation and implicates hypercortisolism as a factor in the pathogenesis of this disorder. Several forms of corticosteroid administration were observed to be a risk factor for CSC. Accordingly, susceptible patients in need of corticosteroids should be advised of the risk of developing acute manifestations of CSC.

Three-Dimensional Evaluation of Vitreomacular Traction and Epiretinal Membrane Using Spectral-Domain Optical Coherence Tomography

PURPOSE To delineate the 3-dimensional (3-D) relationship in vitreomacular traction (VMT) and idiopathic epiretinal membrane (ERM). DESIGN Observational case series. METHODS Forty-eight evaluable eyes of 35 patients with VMT or idiopathic ERM were investigated with spectral-domain (SD) optical coherence tomography (OCT). VMT was defined as focal if the diameter of the vitreous attachment was 1500 microm or less and broad if it was more than 1500 microm. The 3-D OCT representation of vitreomacular interface abnormalities was evaluated. RESULTS Focal VMT was seen in five eyes. Broad VMT was seen in seven eyes. Of these 12 eyes, concurrent ERMs under the detached vitreous were seen in 10 eyes and zones of hyperreflectivity affecting the adjacent detached posterior hyaloid face were seen in 11 eyes. Eyes with focal VMT showed a foveal cavitation, whereas eyes with broad VMT had more widespread cystoid macular edema. Idiopathic ERM was seen in 36 eyes; 30 had complete posterior vitreous detachment (PVD), five had partial PVD associated with attached posterior hyaloid at some peripheral portion of the ERM, and one had no PVD. CONCLUSIONS The SD OCT with 3-D image reconstruction provided unprecedented visualization of VMT and idiopathic ERM. The vitreous attachment to the macula can be subclassified into two subgroups, each having specific induced alterations in retinal anatomy. Most of the eyes with VMT had concurrent ERM, whereas several eyes with idiopathic ERM had attachment of the vitreous to some portion of the ERM, which suggests there is significant overlap between VMT and idiopathic ERM.

Outer Retinal Tubulation: A Novel Optical Coherence Tomography Finding

OBJECTIVE To describe tubular structures found in the outer retina seen in a variety of retinal disorders. METHODS Sixty-nine eyes of 63 patients were examined with spectral-domain optical coherence tomography. Optical coherence tomography C-scans were correlated with their corresponding B-scans. The prevalence, number, size, and shape of the tubular structures were determined. RESULTS Branching tubules were identified in the outer retina of 54 patients with age-related macular degeneration and in 9 patients with other diagnoses. The tubules appeared as round or ovoid hyporeflective spaces with hyperreflective borders on the B-scans, measuring 40 to 140 microm high and 40 to 2260 microm wide. Morphologic features ranged from single straight or branching tubules to complex cavitary networks, usually overlying areas of pigment epithelial alteration or subretinal fibrosis. The tubules generally remained stable over time. In a retinal practice specializing in advanced age-related macular degeneration, these structures were identified in 60 of 248 patients (24.2%) seen during a 3-month period. CONCLUSIONS Degenerating photoreceptors may become arranged in a circular or ovoid fashion during a process we propose to term outer retinal tubulation. These changes are apparently common in advanced diseases affecting the outer retina and retinal pigment epithelium. This observation has practical implications because these findings can be misinterpreted as intraretinal or subretinal fluid, possibly prompting unnecessary interventions.

Polypoidal Choroidal Vasculopathy: A Review

More than a quarter century has passed since the original description of polypoidal choroidal vasculopathy (PCV) in 1982 as a peculiar hemorrhagic disorder involving the macula characterized by recurrent subretinal pigment epithelial bleeding. In the ensuing years, numerous reports have described the expanded clinical spectrum of this entity. PCV is the principal vascular composition of patients of pigmented races experiencing neovascular maculopathies, particularly African Americans and Asians. This form of neovascularization is now known to occur in white patients with or without concomitant drusen, and the site of involvement has extended from the peripapillary area to the peripheral fundus. Indocyanine green angiography has made detection of these abnormal vascular changes more reliable and definitive. More precise diagnosis has also led to a better understanding of specific clinical features that distinguish PCV from more typical proliferations of abnormal choroidal vessels. We review the nature of PCV, including its genetic basis, demographic features, histopathology, clinical manifestations, natural course, response to treatments, and the histopathological and genetic bases. We emphasize multimodal ophthalmic imaging of these vessels, in particular fluorescein and indocyanine green angiography and optical coherence tomography.

Treatment of polypoidal choroidal vasculopathy with photodynamic therapy.

Purpose To study the effects of photodynamic therapy using verteporfin in the treatment of patients with subfoveal polypoidal choroidal vasculopathy (PCV). Methods A retrospective chart review of 16 consecutive patients with subfoveal PCV treated with photodynamic therapy using verteporfin was performed. Results The mean age of the patients involved was 70.5 years. The mean follow-up time was 12 months. The visual acuity improved in 9 (56.3 %), remained the same in 5 (31.3 %), and decreased in 2 (12.5 %). The mean change in visual acuity was an improvement of 2.38 lines, a difference that was highly significant (P = 0.004). The change in visual acuity was negatively correlated with increasing age. The final visual acuity was positively correlated with initial acuity and negatively correlated with age. These results were confirmed by multiple linear regression. No patient had any lasting complication from the treatment. Conclusions Subfoveal PCV has no proven method of treatment. Although the follow-up time and the number of patients in this pilot study were limited, the encouraging results and lack of complications suggest that further study is indicated.

Prospective Study of Intravitreal Ranibizumab as a Treatment for Decreased Visual Acuity Secondary to Central Retinal Vein Occlusion

PURPOSE To evaluate intravitreal injection of ranibizumab as a potential treatment for decreased visual acuity (VA) secondary to central retinal vein occlusion (CRVO). DESIGN Prospective, interventional case series. METHODS Patients with CRVO prospectively recruited from a practice were administered intravitreal ranibizumab 0.5 mg (Lucentis; Genentech Inc, South San Francisco, California, USA) at baseline and monthly for two additional doses. The patients were given additional ranibizumab if they had macular edema as determined by optical coherence tomography or any new intraretinal hemorrhage. Patients were evaluated for number of required injections, side effects, changes in VA, and macular thickness. RESULTS There were 20 eyes of 20 patients who at baseline had a mean age of 72.1 years, a mean VA of 45.8 Early Treatment of Diabetic Retinopathy letters, and a mean central macular thickness of 574.6 microm. Of the 20 eyes, five previously had received intravitreal triamcinolone and 11 had received intravitreal bevacizumab (Avastin; Genentech Inc). At 12 months of follow-up, the mean VA improved to 64.3 letters and the central macular thickness decreased to 186 microm (both different than baseline values; P < .001) using a mean of 8.5 injections. The change in macular thickness was not correlated with the change in VA. In one patient with a history of transient ischemic attack, an ischemic stroke developed but no sequela resulted. In another patient, vitreomacular traction developed, but the patient had improved acuity as compared with baseline. There were no infections, retinal tears, or detachments. CONCLUSIONS Intravitreal ranibizumab used over a period of one year improved mean VA, with low rates of adverse events, in patients with CRVO.

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.

Type 3 Neovascularization: The Expanded Spectrum of Retinal Angiomatous Proliferation

Background: Retinal angiomatous proliferation (RAP) is a distinct form of neovascularization in patients with age-related macular degeneration. Lacking definitive sequential histopathologic evidence of its intraretinal versus choroidal origin, the clinical observations of early stages of RAP lesions may provide clues to help further expand our understanding of this entity. Methods: Five eyes of four patients with early Stage 1 RAP were examined. Fundus photography, fluorescein and indocyanine green angiography as well as time-domain and spectral-domain optical coherence tomography were performed. Images were assessed to determine the characteristics of neovascularization in early stage RAP lesions and the response of the lesions to treatment or observation. Results: The analysis of the selected cases suggests a choroidal origin of the neovascular complex with the early formation of a retinal choroidal anastomosis without evidence of underlying occult Type 1 neovascularization. Three eyes responded to a single treatment with intravitreal ranibizumab (0.5 mg) and 2 eyes (1 patient) resolved spontaneously without treatment. Conclusion: The neovascularization in RAP may originate not only from deep retinal capillaries but also from the choroid. We therefore propose the more descriptive term “Type 3 neovascularization” for this entity to emphasize the intraretinal location of the vascular complex and distinguish this type from the two types of neovascularization previously described by J. Donald Gass in his classic text.