Faculty Bibliography

PURPOSE/OBJECTIVE:To describe disorders that can masquerade as multiple evanescent white dot syndrome (MEWDS). DESIGN/METHODS:Retrospective, multicenter case series. PARTICIPANTS/METHODS:Patients who presented with clinical findings compatible with a diagnosis of MEWDS but were ultimately diagnosed with an alternative inflammatory, infectious, or neoplastic disorder. METHODS:Clinical records and multimodal imaging findings including fundus photography, fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and OCT angiography (OCTA) were analyzed. MAIN OUTCOME MEASURES/METHODS:Inclusion criteria to be defined as a masquerade syndrome for MEWDS included the presence of disseminated grayish-white outer retinal spots that were hyperautofluorescent on FAF and associated with ellipsoid zone (EZ) disruption on OCT. RESULTS:Twenty-two eyes of 13 patients were identified. All patients presented with the classic findings of MEWDS listed above. A MEWDS-like presentation was bilateral in nine of 13 patients (69%). Final diagnosis was determined on the basis of additional investigations including serologies and biopsy. These diagnoses included syphilis (three patients), lymphoma (three patients), idiopathic multifocal choroiditis (two patients), idiopathic retinal phlebitis (one patient), idiopathic acute zonal occult outer retinopathy (one patient), sarcoidosis (one patient), tuberculosis (one patient), and cancer-associated retinopathy (one patient). The outer retinal lesions and imaging findings resolved with treatment for the associated systemic disorders. CONCLUSIONS:Widespread grayish-white outer retinal spots associated with hyperautofluorescence on FAF and disruption of the EZ on OCT are not pathognomonic for MEWDS. A high index of suspicion must be maintained for masqueraders of MEWDS, which can include serious inflammatory, infectious, and neoplastic disorders.

PURPOSE/OBJECTIVE:To describe novel spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) linear and planar reflection artifacts produced by hyperreflective crystalline deposits (HCD). METHODS:Imaging from 10 eyes with HCD producing linear and planar artifacts on OCT was retrospectively analyzed. All eyes had SD-OCT (Spectralis HRA + OCT, Heidelberg Engineering, Germany) and SS-OCT angiography (PLEX Elite 9000, Carl Zeiss Meditec, Inc., Dublin, CA) acquired on the same day. The horizontal extent of planar artifacts and the corresponding HCD on B-scans was measured using a digital caliper. Artifact features from HCD in eyes with non-neovascular age-related macular degeneration (AMD) were analyzed and compared to those seen in two eyes with the "onion sign," an OCT signature previously shown to represent cholesterol crystals (CC) in the sub-retinal pigment epithelium-basal laminar space of eyes with neovascular AMD. A third eye with the "onion sign" was imaged with dense B-scan (DB)-OCTA. RESULTS:Ten eyes of ten patients (77.4 ± 8.7 years) with HCD were analyzed. On SS-OCTA, HCD produced linear artifacts of high signal intensity passing through the HCD and spanning the entire scan depth. On SD-OCT, HCD produced planar artifacts located anterior to both the retina and a hyporeflective space representing normal vitreous signal. The horizontal extent of the artifact did not differ significantly from the corresponding HCD on OCT B-scans (P = 0.62). The OCT artifacts produced by the "onion sign" appeared similar to those of HCD. The additional eye with neovascular AMD imaged with DB-OCTA was characterized by a single, vertical, linear false-flow signal crossing retinal layers. CONCLUSIONS:To the authors' knowledge, this is the first description of SD- and SS-OCT/OCTA artifacts corresponding to both HCD and the "onion sign." These artifacts are likely due to highly reflective CC previously shown on histology to correspond to both of these OCT signatures.

PURPOSE/OBJECTIVE:Cuticular drusen (CD) have been associated with manifestations of age-related macular degeneration such as atrophy and neovascularization in the macula. In this study, eyes with CD were followed and investigated for the estimated 5-year risk of progression to sequelae of age-related macular degeneration such as geographic atrophy (GA) and macular neovascularization (MNV). METHODS:A consecutive series of patients with CD were followed for the development of GA and MNV. Whenever possible, they were also studied retrospectively. The patients with CD were categorized into three phenotypic groups. Phenotype 1: eyes had concentrated, densely populated CD in the macular and paramacular area, Phenotype 2: eyes showed scattered CD in the posterior fundus, and Phenotype 3: involved eyes with CD mixed with large drusen (>200 µm). The 5-year incidence of progression was then estimated using a Kaplan-Meier estimator. RESULTS:A total of 63 eyes from 38 patients (35 women with a mean age at presentation of 58.9 ± 14.2 years) were studied and followed for a mean of 40 ± 18 months. Thirteen patients had single eyes with GA (84.5%; 11/13) or MNV (15.5%; 2/13) in one eye at presentation and were subsequently excluded. Geographic atrophy developed in 19.0% (12/63) of eyes and MNV in 4.8% (3/63) of eyes. The cumulative estimated 5-year risk of GA and MNV was 28.4% and 8.7%, respectively. The estimated 5-year incidence of MNV or GA was 12.6%, 50.0%, and 51.6% in Phenotype 1, Phenotype 2, and Phenotype 3, respectively (P = 0.0015, log-rank test). No difference in risk was found in the development of GA or MNV (P = 0.11) between the subgroup of patients presenting with GA or MNV in their fellow eye and those with both eyes included. CONCLUSION/CONCLUSIONS:When patients with CD are followed longitudinally, there was a significant risk of progression to GA or MNV for Phenotype 2 and Phenotype 3. Patients with CD are commonly first diagnosed in the fifth decade of life, and there is a female predominance. Clinicians should use multimodal imaging to detect and be aware of the risk of progression to manifestations of GA and MNV. These risks of GA and MNV suggest that patients with CD may be part of the overall spectrum of age-related macular degeneration.

PURPOSE/OBJECTIVE:To characterize the topographic relationships among vitreous structures, including the premacular bursa, prevascular vitreous fissures, cisterns, and lacunae, in healthy participants using en face and cross-sectional swept-source (SS) OCT. DESIGN/METHODS:Prospective, comparative study. PARTICIPANTS/METHODS:Sixty eyes of 60 healthy participants (age range, 4-35 years). Eyes of individuals younger than 20 years (n = 29) were compared with eyes of individuals 20 years of age or older (n = 31). METHODS:From each study eye, 12 × 12-mm SS OCT volume scans comprising 1024 × 1024 A-scans centered at the fovea were acquired. MAIN OUTCOME MEASURES/METHODS:En face and cross-sectional data were analyzed to characterize topographic relationships between hyperreflective spaces anterior to the vitreoretinal interface. RESULTS:Prevascular vitreous fissures are an almost universal feature of human eyes. Cisterns became more prevalent over the course of the first 20 years (r = 0.49; P = 0.002). In 97% of eyes in individuals older than 20 years, en face and cross-sectional SS OCT showed the premacular bursa and prepapillary gap merge at a distance superior to the optic nerve and then follow a superonasal course anteriorly. However, only 69% of individuals younger than 20 years demonstrated such a connection (P = 0.01). A close topographic relationship of vitreous fissures and cisterns to the underlying vasculature of the posterior pole was visible on en face projections. En face imaging readily distinguished these spaces. Degenerative, eyewall-parallel fissure planes and their course were described for the first time in a 3-dimensional manner. The fissure planes were rare in younger eyes (12%) and significantly more common in older eyes (42%; P < 0.001). CONCLUSIONS:En face SS OCT demonstrated that (1) premacular bursa and Cloquet's canal are not connected in younger patients, but are connected in older patients; (2) prevascular vitreous fissures overly the retinal vessels; and (3) cisterns are continuous with prevascular fissures.

PURPOSE: To report an unusual case of an elderly patient with transient outer retinal disruption resembling bilateral multiple evanescent white dot syndrome. METHODS: Observational case report. Fundus photographs, fluorescein angiography, standard and ultra-widefield fundus autofluorescence, and cross-sectional and en face optical coherence tomography were used to characterize and describe the clinical findings. RESULTS: A 67-year-old woman presented with decreased vision and floaters in her left eye. Best-corrected visual acuity was 20/20-3 in the right eye and 20/80-2 in the left eye. Funduscopic examination showed small deep white dots and foveal granularity of the left eye corresponding to hyperautofluorescent spots on fundus autofluorescence and ellipsoid zone disruption on spectral domain optical coherence tomography. The asymptomatic right eye had evidence of subretinal deposits on spectral domain optical coherence tomography but was otherwise unremarkable. At 4-week follow-up, the patient noted resolution of her symptoms in the left eye but had developed floaters and blurry vision in her right eye. The left eye showed resolving white spots and ellipsoid zone disruption. However, the right eye had new evidence of white spots corresponding to hyperautofluorescent spots on fundus autofluorescence. Spectral domain optical coherence tomography demonstrated subretinal deposits overlying areas of ellipsoid zone disruption. At 8-week follow-up, the patient was asymptomatic in both eyes with best-corrected visual acuity of 20/20 in both eyes. The hyperautofluorescent spots on ultra-widefield fundus autofluorescence had faded with restoration of ellipsoid zone disruption in both eyes and disappearance of subretinal deposits. CONCLUSION: Our case demonstrates multimodal retinal imaging findings resembling multiple evanescent white dot syndrome in an elderly patient. The bilateral presentation, presence of subretinal deposits before symptom onset, and older age of the patient were atypical features for this entity.

To describe the ocurrence of Bartonella-associated neuroretinitis secondary to non-feline pet exposure, we retrospectively reviewed medical records and imaging from patients with a clinical and serologic diagnosis of Bartonella henselae (BH). Retinal imaging included color fundus photography, optical coherence tomography (OCT) and fluorescein angiography (FA). Four eyes of two patients with cat-scratch disease were included in this study, with a mean age of 35 years. The mean follow-up was 13 months, after presentation of infectious neuroretinitis. Both patients suffered from bilateral neuroretinitis after direct contact with family pets (ferret and guinea pig). All patients were treated with a long-term systemic antimicrobial therapy. Visual acuity in all improved to 20/30 or better at six months. In conclusion, humans may develop cat-scratch disease when they are exposed to Bartonella henselae (BH) in the saliva of infected cats or BH-containing flea feces reaching the systemic circulation through scratches or mucous membranes. As the cat flea (Ctenocephalides felis) may reside on non-feline mammals, Bartonella-associated neuroretinitis may result from contact with other furred family pets.

PURPOSE: Congenital retinal macrovessels are large aberrant retinal blood vessels that cross the horizontal raphe and can traverse the central macula. Using multimodal imaging and optical coherence tomography angiography, we describe 2 cases of congenital retinal macrovessel associated with macroaneurysms. METHODS: Two patients presented for evaluation and were found to have congenital retinal macrovessels associated with macroaneurysms. Color photography, optical coherence tomography, fundus autofluorescence fluorescein angiography, and optical coherence tomography angiography were performed and used to establish the diagnosis and monitor resolution at follow-up visits. RESULTS: The first patient presented with central vision loss in the right eye and was noted to have a ruptured macroaneurysm and scattered microaneurysms along the course of a venous macrovessel. After 3 months of observation, the patient's vision improved. The second patient presented for evaluation of a cataract in her left eye and was incidentally found to have an arterial macrovessel in her right eye with an associated macroaneurysm. Both cases demonstrated an intricate capillary network in the central macula best visualized on optical coherence tomography angiography. CONCLUSION: Macroaneurysms can occur on both arterial and venous macrovessels. After rupture of these lesions, hemorrhage and exudation can resolve with observation alone. Macrovessels can also present with microaneurysms. Optical coherence tomography angiography can effectively image the complex capillary network associated with these vascular anomalies.

Purpose : Age-related macular degeneration (AMD), a leading cause of blindness, is characterized by the formation of drusen. Subretinal drusenoid deposits (SDD) sit over the retinal pigment epithelium, are a proven risk factor for AMD, and can be visualized on cross-sectional spectral domain optical coherence tomography (SD-OCT). We are evaluating the relationship between SDD and serum risk factors for cardiovascular disease (CVD) in AMD. Methods : 58 subjects (ages of 50-90), diagnosed with AMD on two successive examinations, were recruited prospectively, provided blood samples and underwent SDOCT. The presence of SDD was determined on SD-OCT by an experienced examiner, and a panel of serum risk factors performed: Total Cholesterol (TC), Triglycerides (TG), HDL, VLDL, LDL Direct and high sensitivity C-reactive protein (hs-CRP). Independent t-tests were performed on these results. Results : 25 of 58 subjects were found to have SDD present on SD-OCT. Independent ttests demonstrated a significant association (p<0.05) of high TC (>149 mg/dL) (p=0.01) and low HDL (<39mg/dL) (p=0.02) in subjects with SDD compared to subjects without SDD. Post hoc analysis showed that of patients with high TC, 52% had SDD and 22% did not have SDD present (p=0.02); of patients with low HDL, 4% had SDD, 12% did not (p=0.04); of patients with high LDL-direct, 72% had SDD and 55% did not have SDD (p=0.05). Results for TG and hsCRP were inconclusive. Conclusions : The relationship of TC and AMD is inconsistently reported in the literature, with no demonstrated difference between the phenotypes of AMD. Our results demonstrate that high TC is a specific and significant risk factor for AMD with SDD compared to AMD without SDD. High TC is also a strong risk factor for CVD. Therefore, the leading cause of blindness (AMD) can now be connected to the leading cause of death (CVD) through its SDD phenotype, which may be an effective ophthalmic predictor for future CVD. High LDL is a strong risk for CVD as well, and the risk for SDD also approached significance. High HDL is a known risk for AMD, and per our study, may confer even greater risk for SDD. One limitation of our study is that the groups were not matched for other independent CVD risk factors such as hypertension and smoking history, which