Faculty Bibliography

BACKGROUND: Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor (VEGF), has been given via intravitreal injection as an off-label therapy for both neovascular age-related macular degeneration and for macular edema secondary to retinal vascular disease. The authors describe three patients with macular edema secondary to retinal venous occlusion whose edema initially responded to intravitreal bevacizumab but subsequently recurred in excess of that observed before treatment. METHODS: This is a retrospective case series of three patients with macular edema secondary to retinal vein occlusion treated with intravitreal bevacizumab. RESULTS: In all three patients, the rebound retinal edema observed was more pronounced than that present before treatment. CONCLUSION: These cases suggest a potential limitation of using relatively short-acting VEGF antagonists in retinal vascular disease of a chronic nature. Frequent repeated injections may be required to prevent a rebound effect with no clearly defined endpoint. Until the long-term safety of multiple injections of these agents is established, the authors recommend caution in using this treatment strategy

PURPOSE: The etiology and genetic cause of pseudo-vitelliform macular detachment with cuticular drusen (PVMD/CD) are unknown; nor is it clear if this phenotype represents a separate disease entity, or is a sub-phenotype of disorders with overlapping clinical presentation. To answer this question, we screened a cohort of patients affected with PVMD/CD for variation in six plausible candidate genes (ABCA4, VMD2, TIMP-3, peripherin/RDS, fibulin 5 (FIBL5) and complement factor H (CFH)) associated with diseases of overlapping phenotypes. METHODS: Twenty-eight patients, diagnosed with pseudo-vitelliform macular detachment and cuticular drusen, were evaluated by clinical examination, fundus photography, fluorescein angiography and autofluorescence imaging. DNA from all study subjects were screened for variants in the ABCA4, VMD2, TIMP-3, peripherin/RDS, FIBL5 and CFH genes by a combination of DHPLC, array screening and direct sequencing. RESULTS: All patients presented with cuticular drusen; pseudo-vitelliform detachment was seen in 21 cases, while atrophic changes following regression of the detachment were seen in the remaining 7 subjects. Visual acuity ranged from 20/20 to CF. The screening revealed an I32V mutation in peripherin/RDS in one patient and 2ABCA4 variants, T897I and G1961E, in 2 more patients. No amino acid-altering variants were detected in VMD2, TIMP-3, and FIBL5 genes. The frequency of the CFH Y402H variant in this cohort corresponded to that detected in the general population. CONCLUSIONS: Screening of 6 candidate genes detected possibly disease-associated mutations in only 3/28 (10.7%) of patients presenting with PVMD/CD, eliminating these genes as causal for this phenotype

PURPOSE: To compare noninvasive autofluorescence (AF) photography with conventional fundus photography and fluorescein angiography (FA) in the detection of basal laminar drusen (BLD). METHODS: A retrospective case review of 20 patients with BLD studied with AF and conventional imaging was performed. Three selected patients with different degrees of BLD are presented. AF imaging employed an excitation filter at 580 nm and a barrier filter at 695 nm with acquisition by a Topcon 50X fundus camera. Corresponding detail regions in each image were enlarged for comparison. The AF detail image was registered by a projective transformation in Matlab (Mathworks 7.0, Natick, MA) with the color photograph/red free photograph (RF) and/or FA image detail for exact superimposition in Photoshop and lesion comparison. RESULTS: Each visible drusen in the color or RF photograph corresponded when superimposed to a focal hypoautofluorescent lesion in the AF image. However, similar to the starry sky pattern in FA, the AF lesions significantly outnumbered the clinically evident drusen. When BLD lesions were not advanced enough to show the classic starry sky fluorescein hyperfluorescence, the BLD were detectable with AF. CONCLUSIONS: In our case series, AF imaging demonstrated a higher level of sensitivity when compared with conventional fundus photography and is less invasive than FA for the detection of BLD. Fundus AF, therefore, is valuable for diagnosing and following BLD, particularly since these patients are at risk for development of pseudovitelliform detachment which may simulate CNV

PURPOSE: To determine the effect of an adrenocorticoid antagonist (ketoconazole) in the treatment of patients with central serous chorioretinopathy (CSC). METHODS: Ketoconazole was given at an oral dose of 600 mg per day for 4 weeks. Laboratory monitoring included 24-hour urinary cortisol and liver function tests at baseline, 4 weeks, and 8 weeks. Changes in greatest linear dimension were followed with fluorescein angiography at baseline, 4 weeks, and 8 weeks. Posterior pole anatomy was assessed with optical coherence tomography at baseline, 4 weeks, and 8 weeks. Ophthalmic examination and best-corrected visual acuity were assessed at each interval visit. RESULTS: Median visual acuity in the study eye remained stable at 20/40 throughout the 8-week follow-up. Median lesion height and greatest linear dimension were stable at 4 weeks and decreased at 8 weeks. CONCLUSION: Ketoconazole lowered endogenous cortisol after 4 weeks of 600 mg daily. While median visual acuity, lesion height, and greatest linear dimension remained unchanged during the month of drug treatment, there may have been a delayed therapeutic response seen at 8 weeks

PURPOSE: To determine the results of intravitreal bevacizumab injections for the management of choroidal neovascularization (CNV) in patients with pseudoxanthoma elasticum (PXE)-associated angioid streaks. METHODS: A consecutive series of patients with PXE and CNV were managed with intravitreal bevacizumab injection (1.25 mg per 0.05 cc). The main outcome measures were visual acuity and greatest lesion height as measured by optical coherence tomography (OCT). RESULTS: Nine eyes of nine consecutive patients received intravitreal bevacizumab (1.25 mg/0.05 mL) injections. The mean follow-up time was 6 months, during which eyes received an average of 1.8 injections. The baseline visual acuity was a mean of 20/368 and improved to 20/289 at the last visit (P = 0.056). Visual acuity either improved or stabilized in all 9 eyes (100%). Serial OCT measurements in 8 eyes showed a mean of 353 microm at baseline, which decreased to 201 mum at the last visit (P = 0.012). No complications were noted. CONCLUSIONS: These short-term results support the use of intravitreal bevacizumab for the management of CNV in patients with PXE. Continued experience with intravitreal bevacizumab in this population will help establish its longer-term efficacy and better define the potential need for serial injections to maintain these results

PURPOSE: To evaluate the short-term outcomes after intravitreal ranibizumab (Lucentis; Genentech, Inc., South San Francisco, CA) injection in patients with neovascular age-related macular degeneration. METHODS: A review of data for consecutive patients who received intravitreal ranibizumab injection was conducted. The main outcome measures were mean visual acuity and central macular thickness at 3 months compared with those at baseline. Response to ranibizumab therapy was evaluated with particular attention to prior treatment with bevacizumab (Avastin; Genentech, Inc.). RESULTS: Mean baseline visual acuity of 231 eyes of 231 patients was 20/152, and 189 patients (81.8%) had undergone prior treatment, with 153 (65.4%) having received intravitreal bevacizumab. Mean visual acuity at 3 months, available for 203 patients (88%), was 20/126 (P = 0.004). Mean visual acuity for 98 patients treated with bevacizumab within 3 months before ranibizumab injection was 20/100 at baseline and 20/98 at 3 months (P = 0.35). Mean baseline central macular thickness was 278 microm for all patients and improved to 211 microm at 3 months (P < 0.001). Macular thickness decrease was noted irrespective of previous bevacizumab therapy. CONCLUSION: Ranibizumab therapy was associated with significant improvements in mean visual acuity and central macular thickness for the group of all patients. Patients who had received bevacizumab treatment within 3 months before initiating ranibizumab treatment had stability of, but no improvement in, visual acuity

PURPOSE: To evaluate the efficacy of selective treatment with indocyanine green (ICG) angiography-guided photodynamic therapy (PDT) with verteporfin for polypoidal choroidal vasculopathy (PCV). METHODS: In this retrospective consecutive series, 30 eyes of 30 patients with PCV were included. Complete ocular examination, digital fluorescein angiography (FA), ICG angiography, and optical coherence tomography were performed at baseline and at standard intervals thereafter. ICG angiography-guided PDT was performed on all eyes. Only the area of the active PCV or 'hot spot' evident on the ICG angiogram was treated. A spot size was chosen to cover the active neovascular lesion with a 200-mum border. Retreatment was performed when angiography revealed a recurrent lesion. RESULTS: Thirty eyes with PCV were treated and followed for 1 year. Mean age of the patients was 75 years (range, 55-90 years). These patients were all classified as having occult choroidal neovascularization (CNV) with FA and polypoidal CNV with ICG angiography. Improvement of vision (>or=3 lines) was achieved in 15 eyes (50%). Nine eyes had stable vision (30%), and 6 eyes (20%) had a decrease in vision (>or=3 lines). Repeated treatment was required in 15 eyes (50%) for an average of 2.2 treatments in 1 year. CONCLUSION: This study indicates that stabilization or improvement of vision is achieved in most eyes (80%) with neovascular AMD from PCV after selected ICG angiography-guided PDT. These outcomes compare very favorably with those in previous reports on the treatment of occult CNV. Reduced collateral damage to the choriocapillaris and reduced upregulation of vascular endothelial growth factor are presumed to be the explanation for this apparently better outcome. Further studies with longer follow-up are warranted to investigate the long-term efficacy in these conditions

PURPOSE: To describe a previously unreported clinical entity superficially resembling macular serpiginous choroiditis but with a distinct presentation and clinical course. DESIGN: Retrospective observational case series. PARTICIPANTS: Six patients, 50 to 68 years old, exhibiting this entity who were seen at 5 different centers from 1984 to 2006. METHODS: Review of medical records. MAIN OUTCOME MEASURES: Best-corrected visual acuity (VA) and clinical and angiographic findings. RESULTS: The lesions in our patients are similar to those of acute macular serpiginous choroiditis. Our patients had well-delineated whitish plaquelike lesions involving the macula and sparing the peripapillary areas of both eyes. In contrast to serpiginous choroiditis, VA remained good despite early involvement of the fovea until complications related to choroidal neovascularization or pigmentary mottling developed. Angiographic characteristics and the clinical course were also atypical. Fluorescein angiography revealed well-defined early hypofluorescent areas that partially filled in in the late phase. Indocyanine green angiography showed the hypofluorescence to be persistent. Unlike serpiginous choroiditis, the white macular lesions faded over a period of months to years, whereas the characteristic angiographic findings often persisted longer. Choroidal neovascularization developed in 11 of 12 eyes, with subsequent conversion to disciform macular scars in 9 of 12 eyes. Unlike serpiginous choroiditis, none of the eyes showed chorioretinal scar formation unless related to choroidal neovascularization. CONCLUSION: Persistent placoid maculopathy has features resembling macular serpiginous choroiditis but differs in its clinical course and effect on VA. It appears to be a new entity. The majority of eyes develop choroidal neovascularization that results in loss of central vision

PURPOSE: Discreet chorioretinal spots, neovascular maculopathy, peripapillary atrophy and peripheral curvilinear pigmentary-atrophic streaks are characteristic of Multifocal Choroiditis. We report the presence of curvilinear streaks in the posterior pole. METHODS: Observational series. RESULTS/CONCLUSIONS: Like chorioretinal discreet spots, peripheral curvilinear atrophic-pigmentary streaks may also appear in the posterior fundus, including the macular region, in Multifocal Choroiditis