Faculty Bibliography

OBJECTIVE: To analyze the frequency of major age-related macular degeneration (AMD)-associated alleles in patients with multifocal choroiditis (MFC). METHODS: A cohort of 48 patients with MFC was compared with previously characterized cohorts of patients with advanced AMD (368 samples) and matched unaffected controls (368 samples). Allele and genotype frequencies of single nucleotide polymorphisms for the following AMD-associated alleles were evaluated: risk alleles in complement factor H (CFH) gene (Y402H and IVS14) and LOC387715/HTRA1 gene on 10q26 (A69S) and protective alleles in CFH (IVS1, IVS6, and delCFHR1-3) and complement factor B loci (H9L and R32Q). RESULTS: Frequencies of all major AMD-associated alleles in the CFH locus indicate a strong, statistically significant association of CFH gene single nucleotide polymorphisms and MFC. However, the same analysis for the single nucleotide polymorphisms in complement factor B and 10q26 loci matched the results in the control group. CONCLUSIONS: Like AMD, the MFC phenotype is strongly associated with the major alleles/haplotypes in the CFH locus. Clinical Relevance We report compelling evidence of a strong association between CFH polymorphisms and MFC, which contributes to the understanding of MFC pathogenesis and suggests new potential therapeutic targets

PURPOSE: To describe a method to obtain images of the choroid using conventional spectral-domain (SD) optical coherence tomography (OCT) and to evaluate choroidal thickness measurements using these images. DESIGN: Observational case series. METHODS: The images were obtained by positioning the SD OCT device close enough to the eye to obtain an inverted representation of the fundus in healthy volunteers who did not have pupillary dilation. Seven sections, each comprised of 100 averaged scans, were obtained within a 5- x 15-degree rectangle centered on the fovea. The choroidal thickness under the fovea in each image was measured by independent observers. RESULTS: The choroidal thickness could be evaluated in every subject's choroidal image. The mean choroidal thickness under the fovea was 318 microm in the right eye and 335 microm in the left eye. The choroidal thickness showed a high correlation in both eyes (r = 0.82; P < .001). The correlation between the measurements performed by the independent observers was highly significant (right eye, r = 0.93; left eye, r = 0.97; P < .001 for both). CONCLUSIONS: This method provides detailed, measurable images from the choroid, a structure that heretofore has been difficult to image in clinical practice.

PURPOSE: To examine the ultrastructural correlates of spectral-domain optical coherence tomography (SD-OCT) findings in patients with vitreomacular traction (VMT). DESIGN: Observational case series. METHODS: Retrospective analysis of six eyes of consecutive patients who underwent vitrectomy surgery for VMT was performed in this single-center, noncomparative study. One patient had a concurrent macular hole. Preoperative assessment included SD-OCT examination with 3-dimensional image reconstruction. During surgery the vitreous cone was dissected from the vitreous body using scissors, then removed from the surface of the retina with a combination of sharp dissection and peeling, and subsequently submitted for histologic and transmission electron microscopic processing. RESULTS: SD-OCT showed prominent vitreal-foveal adhesion in all six eyes. Each eye had an epiretinal membrane (ERM) under the detached perifoveal posterior vitreous detachment. In all eyes this ERM appeared to course up the cone of attached vitreous and along the back surface of the posterior vitreous face. Ultrastructural analysis showed fibrocellular proliferations in the vitreous specimens in all six cases, which included retinal pigment epithelium (RPE) cells (five eyes), fibrocytes (four eyes), and macrophages (three eyes). CONCLUSIONS: The adhesion between the vitreous and fovea in vitreomacular traction syndrome is accompanied by fibrocellular proliferation along the exposed surfaces of the inner retina and the posterior surface of the vitreous. This fibrocellular proliferation may augment the adhesion between the vitreous and fovea, and may account for the prominent OCT signal seen along the posterior surface of the vitreous in these cases

OBJECTIVE: To report the results of intravitreous bevacizumab (Avastin) treatment for choroidal neovascularization (CNV) from causes other than age-related macular degeneration (AMD). METHODS: We performed a retrospective analysis of eyes that received intravitreous bevacizumab, 1.25 mg, for subfoveal non-AMD CNV at a referral-based retinal practice. Repeated treatment with intravitreous bevacizumab occurred if there were signs of persistent or recurrent exudation. The main outcome measure was visual acuity (VA). RESULTS: The study included 39 eyes of 36 patients with subfoveal CNV secondary to multifocal choroiditis (n = 12), angioid streaks (n = 11), myopic degeneration (n = 10), idiopathic disease (n = 4), or other disease (n = 2). The median baseline VA was 20/60 (logMAR, 0.48). The mean follow-up was 58.8 weeks, and the mean number of injections per eye was 3.4. After 3-month follow-up, the median VA was 20/30 (logMAR, 0.18) (P = .004 vs baseline). At last follow-up, the median VA was 20/40 (logMAR, 0.30). This remained an improvement compared with baseline (P < .02) but was worse than 3-month follow-up (P < .03). There was no correlation between underlying diagnosis and VA change during follow-up. CONCLUSION: Subfoveal CNV secondary to non-AMD causes treated with intravitreous bevacizumab responded favorably and similarly, despite varying underlying etiologies

PURPOSE: To investigate the correlation between visual field (VF) defects in diseases of the acute zonal occult outer retinopathy (AZOOR)-complex and their spectral-domain optical coherence tomographic (OCT) findings. DESIGN: Observational case series. METHODS: Patients with AZOOR, multiple evanescent white dot syndrome (MEWDS), and multifocal choroiditis and panuveitis (MCP) examined in a private practice retinal referral center had threshold VF testing and spectral-domain OCT examination performed using a device capable of obtaining a block of 128 B-scans in a 6 x 6-mm region centered on the optic nerve and macula. The areas of defects in the boundary between the inner segments (IS) and the outer segments (OS) of the photoreceptors, termed the IS/OS boundary, were compared with the VF defects measured. RESULTS: There were 18 evaluable eyes among one patient with MEWDS, two with AZOOR, and seven with MCP. In the 14 eyes with blind spot enlargement [corrected] corresponding IS/OS boundary defects were found in the [corrected] peripapillary region, while no IS/OS boundary defects were found in the four [corrected] eyes without blind spot enlargement. IS/OS boundary defects were seen over chorioretinal scars and areas of neovascularization and no widespread defects were seen [corrected] elsewhere in the fundus. The IS/OS boundary defects showed improvement, as did the blind spot enlargement, spontaneously in the patient with MEWDS and after treatment with immunosuppression in the patients with AZOOR. CONCLUSION: The spectral-domain OCT finding of IS/OS boundary defects, implicating photoreceptor OS perturbation, appears to explain the blind spot enlargement in patients with AZOOR-complex diseases. These defects are not necessarily permanent

PURPOSE: To examine the relationship between visual acuity and morphologic characteristics of macular holes as determined using spectral domain optical coherence tomography (SD OCT). METHODS: A retrospective analysis was performed of eyes with open and closed macular holes at a single, referral-based retina practice. The main outcome measures included best-corrected Snellen visual acuity and SD OCT findings, including the size of the macular hole and the disruption of the junction between inner segments (ISs) and outer segments (OSs) of the photoreceptors. RESULTS: The mean visual acuity for eyes with open (n = 24) and closed (n = 17) macular holes was 20/166 (range, 5/400 to 20/40) and 20/39 (range, 20/80 to 20/25), respectively. The mean macular hole diameter was 859 microm. A disruption of the IS-OS junction was observed in all eyes, and this disruption had a mean diameter of 1,947 microm in eyes with an open macular hole and 626 microm in those with a closed macular hole. There was a negative correlation between both the size of the macular hole (P < 0.001) and the IS-OS disruption (P = 0.01) and visual acuity in eyes with open macular holes. In eyes with closed macular hole, the size of the IS-OS disruption was not correlated with visual acuity (P = 0.82). CONCLUSIONS: The photoreceptor layer appears to be involved for a much larger area than that occupied by the macular hole itself. The abnormality in the IS-OS boundary line may reflect perturbation of a higher level of retinal organization and not an absolute loss of photoreceptor OSs

PURPOSE: To determine the incidence of endophthalmitis following intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents. DESIGN: A retrospective interventional case series. METHODS: A total of 10,254 intravitreal anti-VEGF injections (406 pegaptanib, 3,501 bevacizumab, and 6,347 ranibizumab) were performed from January 5, 2005 to October 18, 2007. The number of the injections was determined from the injection log books and billing records. The injections were performed as an office based procedure with use of povidone-iodine as a part of preinjection preparation. Preinjection antibiotics, eye drape, or surgical attire were not used. The main outcome measures were the incidence of suspected and proven endophthalmitis. RESULTS: There were three cases of suspected endophthalmitis, one case following bevacizumab injection and two cases following ranibizumab injection. There was no case of culture-proven endophthalmitis. All three patients regained their preinjection visual acuity. The incidence of suspected endophthalmitis was 0.029% (95% confidence interval, 0.006% to 0.085%). There was no difference in the incidence of endophthalmitis between ranibizumab and bevacizumab injections (P = .6). CONCLUSIONS: Although there is no consensus regarding the intravitreal injection procedure technique, the incidence of suspected endophthalmitis was very low in a large series of injected patients in a community setting and the incidence compares favorably with that reported in clinical trials where much more extensive preinjection preparation was mandated. We found no difference in the endophthalmitis risk of patients receiving bevacizumab as compared with ranibizumab