Faculty Bibliography

OBJECTIVE: To describe the clinical and imaging findings in patients with focal choroidal excavation. METHODS: Retrospective observational case series. The medical records of 12 patients (13 eyes) with focal choroidal excavation were reviewed. Clinical histories and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and enhanced depth imaging spectral-domain optical coherence tomography) were analyzed. RESULTS: The mean age of the patients was 45 years (range, 22-62 years). Four patients were Asian. Mean visual acuity was 20/31 (range, 20/20 to 20/100). Mean refractive error was -3.54 diopters (D) (range, 6.00 to -8.00 D). One patient had bilateral involvement. All patients manifested varying degrees of foveal pigmentary changes that were usually hypoautofluorescent on fundus autofluorescence images. Fluorescein angiographic findings varied with degree of retinal pigment epithelial alterations. Indocyanine green angiography revealed relative hypofluorescence. In 7 eyes, spectral-domain optical coherence tomography revealed outer retinal layers conforming to retinal pigment epithelial alterations within the excavation. In the other 6 eyes, spectral-domain optical coherence tomography revealed a separation between the outer retina and the retinal pigment epithelium within the excavation. In 7 eyes studied with enhanced depth imaging spectral-domain optical coherence tomography, there was no evidence of scleral ectasia. Mean choroidal thickness of the uninvolved choroid was thicker than normal at 319 mum (range, 244-439 mum). All lesions remained stable except for in 1 eye, which had findings of central serous chorioretinopathy and secondary type 2 (subretinal) neovascularization. CONCLUSION: Focal choroidal excavation is a newly described idiopathic entity in eyes having 1 or more focal areas of choroidal excavation. In some patients, there may be an association with central serous chorioretinopathy. Although most lesions remain stable, secondary choroidal neovascularization may occur.

PURPOSE: To describe the retinal imaging findings in the index patient with Heimler syndrome (OMIM #234580). DESIGN: Non-interventional case report. METHODS: A 29-year-old woman with Heimler syndrome developed bilateral vision loss. Fluorescein angiography (FA), fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) and electroretinography (ERG) were performed to assess the retinal anatomy and function. RESULTS: FA showed mottling of the retinal pigment epithelium (RPE) in the posterior pole and periphery of the retina. FAF revealed hyper and hypoautofluorescent dots corresponding to the RPE mottling observed on FA. SD-OCT documented loss of the inner/outer segments boundary, and RPE thinning. ERG testing excluded generalized rod-cone dysfunction. CONCLUSION: We report an adult-onset macular dystrophy in one of the previously reported patients with Heimler syndrome and hypothesize that this syndrome is probably an expression of a ciliopathy.

PURPOSE: To investigate the association of the rs2301995 haplotype-tagging single nucleotide polymorphism (htSNP) in the elastin gene (ELN) with polypoidal choroidal vasculopathy (PCV) in European-American patients. METHODS: Association analysis of allele and genotype frequencies, determined by TaqMan assays, was performed for the rs2301995 haplotype-tagging single nucleotide polymorphism (htSNP) in the ELN locus in fifty-six patients with PCV, 368 patients with advanced age-related macular degeneration (AMD) and 368 age- and ethnically-matched unaffected controls. RESULTS: The ELN rs2301995 SNP was not statistically significantly associated with the PCV phenotype (P = 0.9). The frequency of the minor allele of the rs2301995 SNP was practically identical in the PCV, AMD and control groups (6.3% vs. 5.4% vs. 7.1%). CONCLUSION: The PCV phenotype in European-American patients is not associated with rs2301995 SNP in the ELN locus.

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 evaluate long-term effectiveness and safety of intravitreal injection of ranibizumab as a potential treatment for decreased visual acuity secondary to central retinal vein occlusion. METHODS: In this prospective interventional case series, patients with central retinal vein occlusion were administered intravitreal ranibizumab 0.5 mg at baseline and monthly for 2 additional doses. Thereafter, the patients were given additional ranibizumab if they had macular edema by optical coherence tomography, leakage during fluorescein angiography, or any intraretinal hemorrhage. RESULTS: There were 35 eyes of 35 patients who at baseline had a mean visual acuity of 44.2 Early Treatment Diabetic Retinopathy Study letters and a mean central macular thickness of 638 mum. At 12 months, mean visual acuity of 32 eyes improved by 16.5 letters and macular thickness decreased to 164 mum (P < 0.001 vs. baseline for each). At 24 months, mean visual acuity of 24 eyes improved by 17.8 letters and macular thickness was 263 mum (P < 0.001 vs. baseline for each). Patients received an average of 10.2 injections during the first year and 6.6 injections during the second year. No cases of endophthalmitis, retinal detachment, or neovascularization were observed. CONCLUSION: Intravitreal ranibizumab caused a significant improvement in visual acuity and central retinal thickness, which persisted for up to 2 years with minimal side effects

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: 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: 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: 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.