Faculty Bibliography

PURPOSE: To correlate clinical observations with multimodal imaging analysis in acquired vitelliform lesions (AVLs) and to elucidate their nature, pathogenesis, and natural course. METHODS: Clinical examination, color fundus photography, fluorescein angiography, near-infrared reflectance, fundus autofluorescence, and spectral-domain optical coherence tomography (SD-OCT) data were retrospectively reviewed for a consecutive series of 90 eyes of 67 patients with an AVL secondary to a variety of diagnoses. RESULTS: In all 90 eyes with AVLs, SD-OCT helped localize the clinically apparent yellowish material to the subretinal space above the retinal pigment epithelial (RPE) band. Only 19 eyes (21.1%) had SD-OCT evidence of subretinal fluid. All eyes exhibited abnormal hyperautofluorescence corresponding to the material seen clinically. In 18 of 72 eyes (25.0%) imaged simultaneously with SD-OCT and near-infrared reflectance imaging, near-infrared hyperreflectivity corresponding to presumed collections of pigment-laden macrophages and RPE cells was observed. Resolution of some AVLs appeared to coincide with progressive thinning of the outer nuclear layer, indicating a gradual loss of photoreceptors. Visual acuity at baseline was best predicted by the subfoveal integrity of the external limiting membrane (P = 0.001) and the inner segment/outer segment junction (P = 0.0002) on SD-OCT. Fluorescein angiography revealed a pattern often mimicking poorly defined (Type 1) choroidal neovascularization. CONCLUSION: Acquired vitelliform lesions occur in a variety of different clinical entities that share common features with multimodal imaging analyses. We propose that both dysfunctional RPE and loss of apposition between the photoreceptor tips and the RPE can interfere with the phagocytosis of shed outer segments. Both this material and pigment-laden macrophages and RPE cells appear to contribute to the yellowish appearance of AVLs. Ongoing photoreceptor loss may in some cases be associated with the spontaneous resolution of an AVL

PURPOSE: To characterize the known appearance of cuticular drusen, subretinal drusenoid deposits (reticular pseudodrusen), and soft drusen as revealed by multimodal fundus imaging and to create an explanatory model that accounts for these observations. METHODS: Reported color, fluorescein angiographic, autofluorescence, and spectral domain optical coherence tomography images of patients with cuticular drusen, soft drusen, and subretinal drusenoid deposits were reviewed, as were actual images from affected eyes. Representative histological sections were examined. The geometry, location, and imaging characteristics of these lesions were evaluated. A hypothesis based on the Beer-Lambert law of light absorption was generated to fit these observations. RESULTS: Cuticular drusen appear as numerous, uniform, round, yellow-white punctate accumulations under the retinal pigment epithelium (RPE). Soft drusen are larger, yellow-white dome-shaped mounds of deposit under the RPE. Subretinal drusenoid deposits are polymorphous light-gray interconnected accumulations above the RPE. Based on the model, both cuticular and soft drusen appear yellow because of the removal of shorter wavelength light by a double pass through the RPE. Subretinal drusenoid deposits, which are located on the RPE, are not subjected to short-wavelength attenuation and therefore are more prominent when viewed with blue light. The location and morphology of extracellular material in relationship to the RPE, and associated changes to RPE morphology and pigmentation, appeared to be the primary determinants of druse appearance in different imaging modalities. CONCLUSION: Although cuticular drusen, subretinal drusenoid deposits, and soft drusen are composed of common components, they are distinguishable by multimodal imaging because of differences in location, morphology, and optical filtering effects by drusenoid material and the RPE.

PURPOSE: To evaluate the subfoveal choroidal thickness after treatment of central serous chorioretinopathy (CSC) visualized by enhanced depth imaging spectral-domain optical coherence tomography (EDI OCT) and indocyanine green angiography (ICGA). DESIGN: Retrospective, comparative series. PARTICIPANTS: Twenty patients (20 eyes). METHODS: The subfoveal choroidal thickness and height of the serous retinal detachment before and after treatment was measured using EDI OCT. Areas of choroidal vascular hyperpermeability were visualized with ICGA. Eyes with classic CSC were treated with laser photocoagulation (LP), whereas eyes with chronic CSC, which are not amenable to LP, were treated with half-dose verteporfin photodynamic therapy (PDT). MAIN OUTCOME MEASURES: Change in choroidal thickness and height of the serous retinal detachment after treatment. RESULTS: There were 12 eyes in the LP group and 8 eyes in the PDT group. The serous subretinal fluid resolved in both groups after treatment. In the LP group, the mean choroidal thickness was 345+/-127 microm at baseline and 340+/-124 microm at 4 weeks, a difference that was not significant (P = 0.2). The mean choroidal thickness in the PDT group increased significantly from 389+/-106 microm at baseline to 462+/-124 microm (P = 0.008) by 2 days after treatment, and then reduced rapidly to 360+/-100 microm (P = 0.001) at 1 week and 330+/-103 microm (P<0.001) after 4 weeks as compared with baseline. Indocyanine green angiography showed decreased hyperpermeability in the PDT group after treatment. CONCLUSIONS: The subretinal fluid resolved in both disease groups; however, the choroidal thickness and hyperpermeability seen during ICGA was reduced after PDT. These findings suggest that PDT reduces the choroidal vascular hyperpermeability seen in CSC and may work by a different mechanism than LP.

PURPOSE: To determine the prevalence and significance of subretinal drusenoid deposits (reticular pseudodrusen) among patients with age-related macular degeneration (AMD). DESIGN: A prospective study with a nested case-control study of consecutive patients with AMD seen in a referral retinal practice. PARTICIPANTS: There were 153 patients with AMD, 131 of whom had > or =1 eye with late AMD, which was defined as either central geographic atrophy or choroidal neovascularization. The control group consisted of 101 patients who did not have AMD as their primary diagnosis, central serous chorioretinopathy, high myopia, retinal detachment, or laser treatment in the macular area. METHODS: The presence of subretinal drusenoid deposits was determined by 2 methods, using the blue channel of color fundus photograph and the spectral domain optical coherence tomography (SD-OCT) sections. Soft drusen were determined from color fundus photographs and confirmed by SD-OCT. MAIN OUTCOME MEASURES: Prevalence of ocular risk factors and subretinal drusenoid deposits in eyes with AMD and their association with late AMD. RESULTS: There were 153 patients who had any form of AMD, with a mean age of 80.3 years. Subretinal drusenoid deposits were diagnosed in the case group in 13 (8.7%) of right and 18 (12.0%) of left eyes using the blue channel of the color photograph and in 58 (38.4%) of right and 54 (35.8%) of left eyes using SD-OCT. Soft drusen and subretinal drusenoid deposits detected by SD-OCT were found to be independently correlated with late AMD (soft drusen odds ratio = 16.66 [P<0.001]; subretinal drusenoid deposits as detected by OCT odds ratio = 2.64 [P = 0.034]). In the control group, subretinal drusenoid deposits were diagnosed in 6 (6.5%) of right and 6 (6.3%) of left eyes using SD-OCT. CONCLUSIONS: Both soft drusen and subretinal drusenoid deposits occur in patients with AMD and both are significantly associated with late AMD. These findings suggest that detection and classification of drusen and consequently assignment of risk should be based on a methodology that includes SD-OCT.

PURPOSE: The purpose of this study was to investigate the fundus autofluorescence and optical coherence tomography findings in eyes with acute zonal occult outer retinopathy (AZOOR). METHODS: A retrospective observational case series of the fundus autofluorescence and spectral domain optical coherence tomography in a series of patients with AZOOR. RESULTS: There were 19 eyes of 11 patients (10 women), who had a mean age of 49.1 +/- 13.9 years. Fundus autofluorescence abnormalities were seen in 17 of the 19 eyes, were more common in the peripapillary area, and were smaller in extent than the optical coherence tomography abnormalities. Nine eyes showed progression of hypoautofluorescence area during the mean follow-up of 69.7 months. The mean thickness of the photoreceptor layer at fovea was 177 microm in eyes with AZOOR, which was significantly thinner than controls (193 microm, P = 0.049). Abnormal retinal laminations were found in 12 eyes and were located over areas of loss of the photoreceptors. The subfoveal choroidal thickness was 243 microm, which is normal. CONCLUSION: Fundus autofluorescence abnormalities in AZOOR showed distinct patterns of retinal pigment epithelial involvement, which may be progressive. Thinning of photoreceptor cell layer with loss of the outer segments and abnormal inner retinal lamination in the context of a normal choroid are commonly found in AZOOR.

PURPOSE: To investigate the frequency of variants in 3 major age-related macular degeneration (AMD)-associated loci in patients of European-American descent with polypoidal choroidal vasculopathy (PCV). DESIGN: Cross-sectional, case-control association study. PARTICIPANTS: Fifty-five patients with PCV, 368 patients with advanced AMD, and 368 age-matched and ethnically matched unaffected controls of European-American descent. METHODS: Association analysis of allele and genotype frequencies, determined by TaqMan assays, was performed for the following haplotype-tagging single nucleotide polymorphisms (htSNPs): risk alleles in the complement factor H (CFH) gene (Y402H and IVS14) in the ARMS2/HTRA1 locus on 10q26 (A69S) and protective alleles in CFH (IVS1 and IVS6) and in the complement factor B/complement component C2 (CFB/C2) locus (IVS10 and H9L). MAIN OUTCOME MEASURES: Allele and genotype frequencies of the htSNPs in the CFH, CFB/C2, and ARMS2/HTRA1 loci. RESULTS: Four AMD-associated haplotype-tagging alleles (rs547154, rs1061170, rs1410996, rs10490924) in the 3 major loci, CFH, CFB/C2, and ARMS2/HTRA1, also were statistically significantly associated with the PCV phenotype (P<0.05). Three other alleles from the same loci (rs4151667, rs529825, rs3766404) showed a trend toward association (P<0.2) but did not reach statistical significance, possibly because of the combined effects of a relatively small sample size and low minor allele frequency in the screened populations. CONCLUSIONS: The PCV phenotype in Caucasian patients is associated with the major alleles/genotypes in the AMD-associated loci, suggesting that PCV and AMD are genetically similar in the tested loci.

PURPOSE: The purpose of this study was to characterize retinal manifestations of optic pit maculopathy using high-resolution optical coherence tomography. METHODS: Consecutive patients with optic pit maculopathy, diagnosed by their typical appearance by ophthalmoscopy, were imaged by color fundus photography and optical coherence tomography. The location and characteristics of any fluid within and under the retina were determined. RESULTS: The mean age of the 16 patients (7 women) was 35.9 years (standard deviation: 18.5 years). The visual acuity ranged from 20/20 to 20/1000 (median, 20/200). Retinal detachment was found in 11 eyes (69%), intraretinal fluid in the outer nuclear layer in 15 eyes (94%), in the inner nuclear layer in 13 eyes (81%), in the ganglion cell layer in 7 eyes (44%), and in the subinternal limiting membrane space in 2 eyes (13%). An outer layer hole was identified in only 3 of 11 eyes (27%) with retinal detachment. CONCLUSION: Fluid from the optic pit can go directly to the subinternal limiting membrane space, ganglion cell layer, inner nuclear layer, outer nuclear layer, or the subretinal space, although the outer nuclear layer is most commonly affected. An outer layer hole appears not to be common in optic pit maculopathy.

PURPOSE:: The purpose of this study was to report long-term results of intravitreal antivascular endothelial growth factor therapy in the management of choroidal neovascularization in patients with angioid streaks associated with pseudoxanthoma elasticum. METHODS:: A consecutive series of patients with pseudoxanthoma elasticum and choroidal neovascularization were managed with intravitreal antivascular endothelial growth factor injections (bevacizumab 1.25 mg/0.05 mL or ranibizumab 0.5 mg/0.05 mL). The main outcome measures were visual acuity and greatest lesion height as measured by optical coherence tomography. RESULTS:: Nine eyes of nine consecutive patients received intravitreal antivascular endothelial growth factor therapy. During the mean follow-up period of 28.6 months, eyes received an average of 8.4 injections. At baseline, the mean visual acuity was 20/368 (median, 20/60) and improved to 20/281 (median, 20/40) at the last visit (P = 0.14). Visual acuity either improved or stabilized in all 9 eyes (100%). Serial optical coherence tomography measurements showed a mean of 353 mum at baseline and decreased to 146 mum at the last visit (P = 0.005). No complications were noted. CONCLUSION:: These long-term results support the use of intravitreal antivascular endothelial growth factor therapy for the management of choroidal neovascularization in patients with pseudoxanthoma elasticum. Continued experience with intravitreal bevacizumab or ranibizumab in this population will help establish long-term efficacy and better define optimal dosing strategies

PURPOSE:: The purpose of this study was to describe intraretinal crystalline deposits detected in eyes with neovascular age-related macular degeneration. METHODS:: A retrospective review of patients seen during a 6-month period with the diagnosis of neovascular age-related macular degeneration was performed to identify patients with intraretinal crystalline deposits, defined as pinpoint refractile bodies within the neurosensory retina. The characteristics of the deposits, including their shape, size, distribution, and location within the retina, were determined by analyzing color and red-free fundus photographs and spectral domain-optical coherence tomography images. RESULTS:: Fourteen eyes of 13 patients with neovascular age-related macular degeneration manifesting intraretinal crystalline deposits were identified. The patients had no history of ocular or systemic disease or prior medication use known to be associated with intraretinal crystals. Intravitreal antivascular endothelial growth factor injection was used in 10 eyes, laser photocoagulation in 3 eyes, and intravitreal triamcinolone in 1 eye. The retinal crystals were detected in the macula overlying or adjacent to the areas of choroidal neovascularization. The crystalline deposits could be localized with spectral domain-optical coherence tomography to both the outer nuclear and the outer plexiform layers. CONCLUSION:: Intraretinal crystalline deposits localized to the outer nuclear and outer plexiform layers can be detected in eyes with a history of neovascular age-related macular degeneration, often after treatment with a variety of different modalities. Potential etiologies of these deposits include residual lipid material from choroidal neovascularization leakage, degenerated Muller cell elements, and because these deposits were found in eyes with assorted forms of treatment, an external factor such as diet may play a role