Faculty Bibliography

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/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:To describe the clinical and multimodal imaging findings of a series of cases of serous macular detachment (SMD) caused by Best disease (BD) masquerading as neovascular age-related macular degeneration or central serous chorioretinopathy that were inappropriately treated with intravitreal anti-vascular endothelial growth factor or laser therapy. This study will also present data to support age-related progressive choroidal thickening in BD patients, which may play a role in the development of SMD in this population. METHODS:Clinical examination and multimodal imaging findings, including color fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and optical coherence tomography-angiography, were reviewed and analyzed. Subfoveal choroidal thickness was also formally measured, and an age-related choroidal thickness analysis was performed and compared with a normal population. RESULTS:Twenty-six eyes of 13 patients (5 women) were included. Median age was 44 years. Nine patients presented with a history of SMD and subretinal fluid recalcitrant to various therapies, including intravitreal anti-vascular endothelial growth factor injections and photodynamic therapy. Best disease was subsequently diagnosed genetically in six patients and by detailed family history in seven. Mean logarithm of the minimum angle of resolution best-corrected visual acuity for all 26 eyes at last follow-up was +0.36 (Snellen equivalent of 20/46). Subfoveal choroidal thickness positively correlated with age for our cohort, increasing linearly at a rate of 25.6 µm per decade (R = 0.64; P < 0.001). Choroidal neovascularization was identified in four eyes on optical coherence tomography angiography, but these eyes did not respond to anti-vascular endothelial growth factor treatment. CONCLUSION/CONCLUSIONS:The diagnosis of BD should be considered in patients presenting with SMD and recalcitrant subretinal fluid masquerading as neovascular age-related macular degeneration or chronic central serous chorioretinopathy to avoid unnecessary treatment procedures. The positive correlation of subfoveal choroidal thickness with age in BD patients may be a factor in the pathogenesis and development of SMD in this population. Recognizing the multimodal imaging features of SMD associated with BD, described in detail in this study, will guide practitioners to the accurate diagnosis of BD and reduce the risk of unnecessary intraocular procedures with potential complications.

PURPOSE/OBJECTIVE:To clarify the role of subretinal drusenoid deposits (SDD; pseudodrusen) in the progression of age-related macular degeneration through high-resolution histology. METHODS:In 33 eyes of 32 donors (early age-related macular degeneration, n = 15; geographic atrophy, n = 9; neovascular age-related macular degeneration, n = 7; unremarkable, n = 2), and 2 eyes of 2 donors with in vivo multimodal imaging including optical coherence tomography, examples of SDD contacting photoreceptors were assessed. RESULTS:Subretinal drusenoid deposits were granular extracellular deposits at the apical retinal pigment epithelium (RPE); the smallest were 4-µm wide. Outer segment (OS) fragments and RPE organelles appeared in some larger deposits. A continuum of photoreceptor degeneration included OS disruption, intrusion into inner segments, and disturbance of neurosensory retina. In a transition to outer retinal atrophy, SDD appeared to shrink, OS disappeared, inner segment shortened, and the outer nuclear layer thinned and became gliotic. Stage 1 SDD on optical coherence tomography correlated with displaced OS. Confluent and disintegrating Stage 2 to 3 SDD on optical coherence tomography and dot pseudodrusen by color fundus photography correlated with confluent deposits and ectopic RPE. CONCLUSION/CONCLUSIONS:Subretinal drusenoid deposits may start at the RPE as granular, extracellular deposits. Photoreceptor OS, RPE organelles, and cell bodies may appear in some advanced deposits. A progression to atrophy associated with deposit diminution was confirmed. Findings support a biogenesis hypothesis of outer retinal lipid cycling.

PURPOSE/OBJECTIVE:To use swept-source optical coherence tomography and swept-source optical coherence tomography angiography to investigate potential relationships between choroidal vascular hyperpermeability (CVH) seen with indocyanine green angiography (ICGA), choriocapillaris flow density, and choroidal thickness in eyes with pachychoroid pigment epitheliopathy. METHODS:Patients with pachychoroid pigment epitheliopathy were prospectively imaged with 12-mm × 12-mm swept-source optical coherence tomography, 12-mm × 12-mm swept-source optical coherence tomography angiographyA, and ICGA. Binarized choriocapillaris OCTA images were superimposed with ICGA images in which CVH area had been isolated. Choriocapillaris flow density within or outside the quadrants of CVH was calculated and the ratio of these two values was determined. The presence of CVH and choroidal thickness was evaluated at 9 locations within a central 3-mm × 3-mm area to explore the relationship between these 2 factors. RESULTS:Ten eyes from 10 patients were enrolled in the present study. Choriocapillaris flow density within quadrants of CVH area was significantly lower compared with quadrants without CVH (P < 0.001). The mean choriocapillaris flow density ratio was 0.86 ± 0.10 (range: 0.65-0.99). From among the 90 locations in 10 study eyes, 48 were within areas of CVH. Choroidal thickness was greater in quadrants of CVH compared with areas without CVH (P < 0.001, 455 ± 122 µm vs. 297 ± 93 µm). CONCLUSION/CONCLUSIONS:Reduced choriocapillaris flow density, increased choroidal thickness, and CVH appear to co-localize in eyes with pachychoroid pigment epitheliopathy.

PURPOSE/OBJECTIVE:To evaluate the subfoveal choroidal thickness (SFCT) and vascular architecture in the fellow eyes of patients with circumscribed choroidal hemangioma (CCH). METHODS:In this retrospective observational study, patients were selected from outpatient ophthalmology clinics at the Memorial Sloan Kettering Cancer Center and Vitreous Retina Macula Consultants of New York. Subfoveal choroidal thickness was measured using enhanced depth imaging spectral domain optical coherence tomography from the outer portion of Bruch membrane to the choroidal-scleral interface. Choroidal vascular architecture was qualitatively examined. The main outcome measure was SFCT in fellow eyes of patients with CCH, which was compared with an age- and gender-matched control group. RESULTS:Thirty-one fellow eyes (15 right eyes and 16 left eyes) of patients with CCH (23 males and 8 females) were examined. The fellow eye had a mean SFCT of 361.2 ± 99.9 μm compared with 252.0 ± 77.6 μm in the control group (P < 0.0001). Vascular architecture was disorganized in 13 (42%) fellow eyes and 1 (3%) control eye (P < 0.0001), with no apparent gradient of vessel sizes or discrete choroidal layers. The normal association between older age and a thinner choroid existed in control eyes but not in fellow eyes. Hemangioma thickness measured by ultrasound and the presence of subfoveal fluid in the CCH eye did not correlate with the fellow-eye SFCT. CONCLUSION/CONCLUSIONS:In patients with CCH, fellow eyes had thicker SFCT when compared with age- and gender-matched control eyes. Choroidal architecture was often irregular, without segmented vascular layers. These findings suggest that inherent choroidal changes may exist in patients with CCH.

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.

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.

PURPOSE: We describe the long-term follow-up of a patient with multifocal Best disease with chronic bilateral serous macular detachment and unusual peripheral findings associated with a novel mutation in the BEST1 gene. METHODS: Case report. RESULTS: A 59-year-old white woman was referred for an evaluation of her macular findings in 1992. There was a family history of Best disease in the patient's mother and a male sibling. Her medical history was unremarkable. Best-corrected visual acuity was 20/20 in her right eye and 20/25 in her left eye. The anterior segment examination was normal in both eyes. Funduscopic examination showed multifocal hyperautofluorescent vitelliform deposits with areas of subretinal fibrosis in both eyes. An electrooculogram showed Arden ratios of 1.32 in the right eye and 1.97 in the left eye. Ultra-widefield color and fundus autofluorescence imaging showed degenerative retinal changes in areas throughout the entire fundus in both eyes. Optical coherence tomography, including annual eye-tracked scans from 2005 to 2016, showed persistent bilateral serous macular detachments. Despite chronic foveal detachment, visual acuity was 20/25 in her right eye and 20/40 in her left eye, 24 years after initial presentation. Genetic testing showed a novel c.238T>A (p.Phe80Ile) missense mutation in the BEST1 gene. CONCLUSION: Some patients with Best disease associated with chronic serous macular detachment can maintain good visual acuity over an extended follow-up. To our knowledge, this is the first report of Best disease associated with this mutation in the BEST1 gene.

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.