Faculty Bibliography

PURPOSE: To investigate the prevalence of sequence variants in the ATM gene and to determine the frequency of major age-related macular degeneration (AMD)-associated variants in CFH, CFB, and 10q26 loci in patients with idiopathic perifoveal telangiectasia (IPT). METHODS: Thirty patients with diagnoses of IPT underwent standard ophthalmologic evaluation that included visual acuity testing, fundus photography, and fluorescein angiography. DNA was screened for variations in the ATM gene by a combination of denaturing high-performance liquid chromatography and direct sequencing. Major AMD-associated alleles in CFH, CFB, and 10q loci were screened by PCR-restriction fragment-length polymorphism. RESULTS: Nineteen female and 11 male patients (average age, 59 years) with a median visual acuity of 20/50 were evaluated. Six patients were of Asian-Indian origin, one was Hispanic, and 23 were of European-American ancestry. Nine of 30 (30%) patients had diabetes mellitus, 18 of 30 (60%) patients had hypertension, and 12 of 30 (40%) patients had a history of smoking. Screening of the ATM gene revealed a null allele in 2 of 23 (8.7%) patients of European ancestry, previously disease-associated missense alleles in 4 of 23 (17.4%) patients, and common missense alleles in 7 of 23 (30.4%) patients. No variants were identified in the ATM gene in patients of Asian or Hispanic origin. Frequencies of major AMD-associated alleles in CFH, CFB, and 10q loci in the IPT cohort were similar to those in the ethnically matched general population. CONCLUSIONS: At least 26%, and maybe up to 57%, of IPT patients of European-American descent carried possibly disease-associated ATM alleles. Vascular risk factors such as hypertension, diabetes, and smoking may be associated with the pathogenesis of the disease

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

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

PURPOSE: To report the occurrence of central serous chorioretinopathy in patients with keratoconus and discuss the possible connection between these two conditions. METHODS: Observational case series. RESULTS: The authors identified three subjects with keratoconus and central serous chorioretinopathy. All patients underwent visual acuity measurement, fundus examination, digital fluorescein angiography, and optical coherence tomography. CONCLUSIONS: Keratoconus and central serous chorioretinopathy are two uncommon diseases, possibly due to dysfunction of epithelium and its basement membrane, which can occur together in some individuals. The authors discuss the possible connection between these two conditions

PURPOSE/OBJECTIVE:We report two cases of macular infarction as a presenting sign of systemic lupus erythematosus (SLE). METHODS:Ophthalmic examination and intravenous fluorescein angiography were supplemented by rheumatology consultations and imaging. RESULTS:Two patients presented with complaints of decreased vision in one or both eyes. Systemic manifestations included fever, rash, and arthralgias, while serologic tests revealed an elevated erythrocyte sedimentation rate and positive antinuclear antibody titers in both cases, confirming the diagnosis of SLE in each case. Ophthalmoscopic changes included cotton-wool spots, intraretinal hemorrhages, and retinal edema. Fluorescein angiography revealed macular infarction with extensive retinal capillary nonperfusion in both patients. CONCLUSION/CONCLUSIONS:Macular infarction is an uncommon but recognized complication of vasculitis associated with SLE. We report two additional cases of newly diagnosed SLE where vision loss secondary to macular infarction was the presenting sign of the disease. SLE should be considered in all patients who present with macular infarction. Visual prognosis is usually poor.

PURPOSE: To describe multifocal choroiditis in two siblings. METHODS: Retrospective case reports. RESULTS: Two sisters presented 10 years apart with multifocal choroiditis. The first sister manifested late findings of multiple punched-out chorioretinal lesions and a quiescent central fibrovascular scar. The second sister presented in the acute phase with multiple creamy yellow lesions near the optic nerve and fovea and with a choroidal neovascular membrane. Both cases were unilateral. DISCUSSION: Multifocal choroiditis is an inflammatory disorder of the inner choroid and retinal pigment epithelium of unknown etiology. There is no gene associated with multifocal choroiditis, and to our knowledge, no cases of relatives with the disease have been reported. CONCLUSION: We describe multifocal choroiditis in two sisters, suggesting a possible genetic or environmental component to this disease. Further study is necessary to better elucidate the etiology of this disease.

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