Faculty Bibliography

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 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 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: To characterize reticular pseudodrusen, a potential risk factor for late age-related macular degeneration. DESIGN: Retrospective, observational case series. PARTICIPANTS: Fifty-eight eyes of 33 patients with pseudodrusen (20 female). METHODS: Consecutive patients with reticular pseudodrusen, diagnosed by their typical appearance and distribution using ophthalmoscopy, the blue channel of color fundus photographs, and near infrared images. The patients were imaged by spectral domain optical coherence tomography (SD OCT), and correlations were made between the near infrared images and the SD OCT images. The SD OCT findings in patients with pseudodrusen were compared with previously reported histologic findings of subretinal drusenoid deposits. The histologic specimens were reevaluated with the additional knowledge of the clinical information. MAIN OUTCOME MEASURES: Spectral domain optical coherence tomography and histologic characteristics of pseudodrusen. RESULTS: The mean age of the 33 patients was 81.7 years. The correlating SD OCT scans showed collections of granular hyperreflective material above the retinal pigment epithelium (RPE), in the subretinal space located primarily between the RPE and the boundary between the inner and outer segments of the photoreceptors (IS/OS boundary). In a more advanced stage, this material formed small mounds that broke through the IS/OS boundary. There were no correlates to the deposits seen under the RPE or in the choroid. These findings were similar in character to previously reported histologic characterization of subretinal drusenoid deposits, which had identified the presence of membranous debris, unesterified cholesterol, and complement within the deposits. CONCLUSIONS: Pseudodrusen seen by clinical examination may be subretinal drusenoid deposits seen by histologic examination. This unexpected location suggests that potential pathophysiologic mechanisms on both sides of the RPE need to be taken into account in theories related to the development of age-related macular degeneration. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references

PURPOSE: The purpose of this study was to investigate the frequency of glaucoma and related conditions in patients with central serous chorioretinopathy (CSC), a condition associated with increased choroidal thickness. METHODS: A case-control study was conducted. Consecutive patients with CSC examined from January 1, 2006, through July 31, 2008, were compared with a sex- and age-matched control group from the same referral practice seen during the same period for the frequency of glaucoma and related conditions. The charts of the cases and the control subjects were reviewed for diagnosis of glaucoma. RESULTS: In 287 patients with CSC, the mean age was 56.8 years and 207 (72.1%) were men. In the control group of 235, the mean age was 59.5 years and 168 (71.5%) were men. Glaucoma was found in 10 of 287 patients (3.4%) with CSC and in 20 of 235 control subjects (8.5%, P = 0.014, odds ratio = 0.39, 95% confidence interval = 0.16-0.89). The mean intraocular pressures were similar in the two groups. However, the number of patients diagnosed with ocular hypertension (0.3% versus 3.4%, P = 0.0076) and the number of patients using pressure-lowering eye drops (3.8% versus 13.2%, P <or= 0.0001) were significantly less in the CSC group than in the control group. CONCLUSION: Glaucoma and related conditions are less frequent in the CSC group than in the control group. In patients with CSC, increased blood supply to the optic nerve from the choroid may be a contributing factor, but there may be differences in the variances in intraocular pressure that cannot be ruled out

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

PURPOSE: To describe a patient with birdshot retinochoroidopathy (BRC) with bilateral choroidal neovascularization (CNV) who was treated with intravitreal injection of bevacizumab and antiinflammatory medications. METHOD: Interventional case report. PATIENT: A 35-year-old woman with bilateral CNV associated with BRC. RESULTS: The patient was treated with intravitreal injection of triamcinolone, photodynamic therapy, and intravitreal injection of bevacizumab in one eye, while the fellow eye was treated with intravitreal injection of triamcinolone. Immunosuppressive therapy was performed in the course of the treatment. Not only did the neovascularization respond, but the birdshot lesions vanished as well. DISCUSSION: BRC can have secondary CNV that, as in the current case, responds favorably to treatment. We serendipitously observed regression of the choroidal inflammatory lesions with intravitreal injection of triamcinolone.

PURPOSE: To report an association between polypoidal choroidal vasculopathy (PCV) and choroidal nevus in two patients. METHODS: Two patients with subretinal exudation associated with a choroidal nevus had a complete ophthalmologic examination, slit-lamp biomicroscopy, color fundus photography, fluorescein angiography (FA), and indocyanine green angiography (ICG). RESULTS: In the two eyes of the two patients with choroidal nevus, choroidal neovascularization with PCV-like characteristics was detected by ICG angiography. CONCLUSIONS: PCV-like vascular changes can be associated with choroidal nevus, and ICG can help delineate the nature of the neovascularization in patients with choroidal nevus.

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