Faculty Bibliography

PURPOSE/OBJECTIVE:To describe the defining features of incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA), a consensus term referring to the OCT-based anatomic changes often identified before the development of complete RPE and outer retinal atrophy (cRORA) in age-related macular degeneration (AMD). We provide descriptive OCT and histologic examples of disease progression. DESIGN/METHODS:Consensus meeting. PARTICIPANTS/METHODS:Panel of retina specialists, including retinal imaging experts, reading center leaders, and retinal histologists. METHODS:As part of the Classification of Atrophy Meeting (CAM) program, an international group of experts analyzed and discussed longitudinal multimodal imaging of eyes with AMD. Consensus was reached on a classification system for OCT-based structural alterations that occurred before the development of atrophy secondary to AMD. New terms of iRORA and cRORA were defined. This report describes in detail the CAM consensus on iRORA. MAIN OUTCOME MEASURES/METHODS:Defining the term iRORA through OCT imaging and longitudinal cases showing progression of atrophy, with histologic correlates. RESULTS:OCT was used in cases of early and intermediate AMD as the base imaging method to identify cases of iRORA. In the context of drusen, iRORA is defined on OCT as (1) a region of signal hypertransmission into the choroid, (2) a corresponding zone of attenuation or disruption of the RPE, and (3) evidence of overlying photoreceptor degeneration. The term iRORA should not be used when there is an RPE tear. Longitudinal studies confirmed the concept of progression from iRORA to cRORA. CONCLUSIONS:An international consensus classification for OCT-defined anatomic features of iRORA are described and examples of longitudinal progression to cRORA are provided. The ability to identify these OCT changes reproducibly is essential to understand better the natural history of the disease, to identify high-risk signs of progression, and to study early interventions. Longitudinal data are required to quantify the implied risk of vision loss associated with these terms. The CAM classification provides initial definitions to enable these future endeavors, acknowledging that the classification will be refined as new data are generated.

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/UNASSIGNED:To describe features of neovascularization in proliferative diabetic retinopathy (PDR) using optical coherence tomography angiography (OCTA). Methods/UNASSIGNED:A retrospective case series was performed in 23 eyes from 21 patients who underwent OCTA of neovascular complexes (NVCs) due to PDR. Eyes were imaged with the DRI Triton swept-source OCTA, Avanti RTVue XR or Cirrus HD-OCT 5000 as part of routine clinical examination. Segmentation was adjusted to include vasculature between the vitreous cavity and the internal limiting membrane (ILM). The presence of NVCs was confirmed by clinical examination and multimodal imaging such as color or red-free fundus photography, fluorescein angiography, multicolor imaging or near-infrared reflectance. Results/UNASSIGNED:Thirty-five NVCs were imaged, of which, 34% were neovascularization of the disc (NVD) and 66% were neovascularization elsewhere (NVE). On structural OCT B-scans, NVE appeared as medium to highly reflective tissue that breached the ILM, while NVD showed highly reflective tissue protruding from the disc in a sea fan configuration. Flow signal was seen on OCTA in all cases of NVE and in 67% of NVD lesions. Areas with minimal or absent retinal flow signal identified retinal nonperfusion areas and were found adjacent to 87% of NVE. Intraretinal microvascular abnormalities (IRMAs) were noted next to 70% of NVE. Absent flow signal was seen in 4 NVD cases showing posterior shadowing and were considered inactive. Conclusion/UNASSIGNED:OCTA appears useful for imaging NVCs, IRMAs, and retinal nonperfusion areas in eyes with diabetic retinopathy. This imaging modality enables noninvasive screening and monitoring of PDR and can obviate the need for additional testing in certain clinical settings.

PURPOSE: To report two cases of choroidal nevi associated with focal choroidal excavation (FCE) and polypoidal choroidal neovascularization (PCN). METHODS: Report of two patients with choroidal nevi showing FCE and PCN who underwent multimodal imaging including color fundus photography, fluorescein angiography, indocyanine green angiography, fundus autofluorescence, spectral domain optical coherence tomography, swept-source optical coherence tomography, and optical coherence tomography angiography. RESULTS: Two patients presented with choroidal nevi associated with FCE and PCN. In the first case, a 74-year-old woman, the nevus had sharp margins, a deep FCE, surrounding drusen, and subretinal exudation at its inferior edge due to PCN that responded well to intravitreal anti-vascular endothelial growth factor therapy. In the second case, a 64-year-old woman, the nevus had ill-defined margins, a shallow FCE, and angiographic evidence of PCN without associated exudation. CONCLUSION: There have been several reports showing an association of either choroidal nevi or FCE with PCN. To our knowledge, there have been no previous reports of FCE identified within choroidal nevi, with or without associated PCN. Since, in one of our cases, the FCE was not apparent on clinical examination, the prevalence of FCE within nevi may be underdiagnosed.

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

PURPOSE/OBJECTIVE:To describe two cases of retinal detachment with hydration folds and discuss the possible cause of these outer retinal abnormalities. METHODS:The medical and imaging records of two patients with retinal detachment and hydration folds were examined. PATIENTS/METHODS:A 43-year-old myopic woman who developed a retinal detachment secondary to a macular hole and a 35-year-old man referred with a rhegmatogenous retinal detachment masquerading as an exudative detachment were each found to have retinal hydration folds. RESULTS:On near-infrared reflectance imaging, the hydration folds appeared similar to eddy currents, and these corresponded to curvilinear outer retinal plications on optical coherence tomography. The photoreceptor outer segments appeared thickened and elongated, and there was apparent lateral expansion of the outer retinal layers. CONCLUSION/CONCLUSIONS:Hydration folds are found in rhegmatogenous retinal detachment and demonstrate reproducible imaging characteristics on near-infrared imaging and optical coherence tomography. The cause for such outer retinal plications is currently unknown. We suspect that they form as a result of hydration of the glycosaminoglycans in the interphotoreceptor matrix, which lies between the photoreceptors. Additional studies are warranted to explore this pathophysiology.

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: 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.