Faculty Bibliography

IMPORTANCE/OBJECTIVE:Although the diagnosis of vitreoretinal lymphoma (VRL) can be challenging, early detection is critical for visual prognosis. OBJECTIVE:To analyze the spectrum of optical coherence tomography (OCT) findings in patients with biopsy-proven VRL and correlate these features with clinical parameters. DESIGN/METHODS:Retrospective cross-sectional study SETTING: Multicenter chart review from 13 retina, uveitis and ocular oncology clinics worldwide over an 11-year period (2008-2019). PARTICIPANTS/METHODS:Patients with a diagnosis of biopsy-proven VRL imaged with OCT at presentation EXPOSURE: The ocular information, systemic information and multimodal retinal imaging findings were collected and studied. MAIN OUTCOME MEASURE/METHODS:Characteristics of VRL on OCT RESULTS: A total of 182 eyes of 115 patients (63 women, mean age 65 years) were included in this study. The disease was bilateral in 81 (70%) patients, and mean baseline visual acuity (VA) was 0.2±0.89 logMAR (Snellen equivalent of 20/32). At baseline, 38 patients (33%) presented with isolated ocular involvement, 54 (45%) with associated central nervous system (CNS) involvement and 11 (10%) with other systemic lymphomatous involvement and an additional 12 (10%) patients presented with both CNS and other systemic involvement. On OCT, tumor infiltration was identified in various retinal layers including lesions in the sub-retinal pigment epithelium (RPE) compartment (91% of eyes), the subretinal compartment (43% of eyes) and the intraretinal compartment (7% of eyes). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:OCT analysis of eyes with vitreoretinal lymphoma identified 3 main regions of retinal infiltration. Sub-RPE location, with or without subretinal infiltration, was the most common pattern of involvement whereas isolated intraretinal infiltration was the least common.

PURPOSE/OBJECTIVE:To report a case of IgG4-related ophthalmic disease, which presented with papillitis and subretinal deposits. METHODS:Observational case report with multimodal imaging. RESULTS:A 52-year-old man with a history of persistent lymphadenopathy presented with decreased vision in his left eye. Funduscopic examination demonstrated cuticular drusen in both eyes and florid edema of the left optic nerve, along with scattered circumscribed grey-yellow subretinal deposits that were distinct from the cuticular drusen. Swept-source optical coherence tomography demonstrated a hyper-reflective subretinal material corresponding to the grey-yellow subretinal deposits on clinical examination along with diffuse outer retinal disruption. Fundus autofluorescence revealed scattered hypoautofluorescence corresponding to cuticular drusen and also larger patches of hypoautofluorescence corresponding to the grey-yellow subretinal deposits. Fluorescein angiography demonstrated hypofluorescence corresponding to the large subretinal deposits and leakage at the optic nerve. Lymph node biopsy demonstrated IgG4-positive plasma cells and elevated serum IgG4 levels leading to a diagnosis of IgG4-related ophthalmic disease. The patient was treated with oral prednisone with subsequent resolution of the optic nerve edema. CONCLUSION/CONCLUSIONS:We describe multimodal imaging of unique retinal and optic nerve findings associated with IgG4-related ophthalmic disease. Our report broadens the spectrum of ocular involvement associated with IgG4-related disease.

PURPOSE/OBJECTIVE:To describe resolution of a subfoveal choroidal cavern after half-dose verteporfin photodynamic therapy for persistent central serous chorioretinopathy. METHODS:Case report. RESULTS:A 43-year-old man was referred for treatment of chorioretinopathy in his left eye. On presentation, swept-source optical coherence tomography demonstrated a serous retinal detachment and a 161-μm-thick subfoveal choroidal cavern showing a characteristic tail of hypertransmission extending posteriorly. Subfoveal choroidal thickness measured 456 μm in the affected eye. Complete resolution of subretinal fluid and the subfoveal choroidal cavern were observed 3 months after half-dose verteporfin photodynamic therapy. Twelve months after treatment, subfoveal choroidal thickness had decreased further to 276 μm, and visual acuity had improved to 20/15. CONCLUSION/CONCLUSIONS:After half-dose verteporfin photodynamic therapy for chorioretinopathy, resolution of subretinal fluid was accompanied by resolution of a subfoveal choroidal cavern at 3 months and a 39.5% reduction in subfoveal choroidal thickness at 1 year.

PURPOSE/OBJECTIVE:To describe three patients with idiopathic multifocal choroiditis (MFC) who showed foci of foveal outer retinal hyperreflectivity on optical coherence tomography. METHODS:Retrospective review of electronic health records and multimodal imaging from three patients with MFC. RESULTS:Three consecutive white patients with MFC (two male and one female) presented with unilateral foveal outer retinal hyperreflectivity in the eye with active MFC. In all cases, the lesions persisted for at least 1 month. Optical coherence tomography demonstrated finger-like projections of hyperreflectivity extending from the retinal pigment epithelium and through disrupted interdigitation and ellipsoid zones into the outer nuclear layer, with some aspects of the lesions reaching the inner limiting membrane. Visual recovery varied in the three affected eyes. CONCLUSION/CONCLUSIONS:Foveal outer retinal hyperreflectivity is a novel optical coherence tomography finding in eyes with active MFC. Additional studies will be required to address the prevalence and prognostic importance of foveal outer retinal hyperreflectivity.

PURPOSE/OBJECTIVE:To clarify the histologic basis of bacillary layer detachment (BALAD) through a review of current literature and an analysis of retinal imaging. METHODS:We reviewed the literature for previous reports of BALAD. An analysis of retinal images was performed to support anatomic conclusions. RESULTS:A total of 164 unique patients with BALAD on optical coherence tomography (OCT) were identified from the published literature. Twenty-two underlying etiologies, all associated with subretinal exudation, were identified. Forty-one different OCT terminologies were found. The defining OCT feature of BALAD was a split at the level of the photoreceptor inner segment myoid creating a distinctive intraretinal cavity. Resolution of BALAD was followed by a rapid restoration of the ellipsoid zone. Histology of age-related macular degeneration eyes suggests that individual photoreceptors can shed inner segments. Further, detachment of the entire layer of inner segments is a common postmortem artefact. We propose that BALAD occurs when outwardly directed forces promoting attachment of photoreceptor outer segments to the retinal pigment epithelium exceed the tensile strength of the photoreceptor inner segment myoid. CONCLUSION/CONCLUSIONS:Our review serves to strengthen the OCT nomenclature "bacillary layer detachment", based on specific reflectance information obtained by OCT and previously published histologic observations.

PURPOSE/OBJECTIVE:To describe the vascular anatomy and intraluminal flow characteristics of segmental retinal arteritis (SRA) using structural and angiographic optical coherence tomography (OCT). METHODS:Retrospective case series of consecutive patients presenting with SRA. All patients were evaluated at presentation with fundus photography, spectral domain OCT, and OCT angiography. One patient was imaged with dense B-scan OCT angiography. RESULTS:Three eyes of three male patients were evaluated. All examinations were consistent with reactivation of ocular toxoplasmosis with an area of active retinochoroiditis adjacent to a focal chorioretinal scar. Spectral domain OCT through areas of SRA noted on clinical examination demonstrated areas of hyperreflectivity circumscribing the affected vessel with a normoreflective lumen. Optical coherence tomography angiography and dense B-scan OCT angiography demonstrated narrowing of the intraluminal flow signal that correlated with areas of segmental hyperreflectivity on spectral domain OCT. Vascular sections proximal and distal to areas of SRA showed normal flow signal. CONCLUSION/CONCLUSIONS:Vessels with SRA demonstrated hyperreflectivity highlighting the vessel wall on spectral domain OCT. Optical coherence tomography angiography showed narrowing of the flow signal within these segments suggesting reduced lumen diameter. Coupling these finding with previous indocyanine green imaging findings in SRA, the collective data suggest the plaques are localized within the vessel wall to either the endothelium or the muscular tunica media without occlusion of the vessel lumen.

PURPOSE/OBJECTIVE:Macular atrophy (MA) of retinal pigment epithelium (RPE) and photoreceptors leads to vision loss in neovascular age-related macular degeneration (nAMD) despite successful treatment with anti-angiogenic agents. To enhance understanding of MA, fortify the cellular basis of fundus autofluorescence (FAF) imaging, and inform management of nAMD, we performed histological analysis of an eye with multimodal clinical imaging and apparent prior exudation due to nAMD. DESIGN/METHODS:Case study and clinicopathologic correlation. SUBJECT/METHODS:A white woman in whom AMD findings of inactive subretinal fibrosis (right eye) were followed for 9 years using FAF and optical coherence tomography (OCT), with no detectable subretinal fluid or other recurrent exudation, and no intravitreal injections before death at age 90 years. METHODS:The right eye was preserved 6.25 hours after death, post-fixed in osmium tannic acid paraphenylenediamine, and prepared for sub-micrometer epoxy resin sections (n=115), with 19 matched to clinical OCT B-scans. MAIN OUTCOME MEASURES/METHODS:Light microscopic morphology of a hyperautofluorescent (hyperFAF) area attributed to prior exudation ("floodplain" hyperFAF), hypoautofluorescent (hypoFAF) spots of MA, and areas of unremarkable FAF. RESULTS:Floodplain hyperFAF was visible throughout the 9 years follow-up, with several hypoFAF atrophic spots expanding within it over time. The hyperFAF pattern corresponded to outer retinal atrophy (ORA) on OCT and photoreceptor loss over dysmorphic yet continuous RPE in histology. The hypoFAF spots inside the floodplain corresponded to complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) on OCT and loss of both photoreceptors and RPE in histology. In contrast, areas of unremarkable FAF showed continuous RPE accompanied by full-length photoreceptors and a thick outer nuclear layer. CONCLUSION/CONCLUSIONS:This direct clinicopathologic correlation for FAF imaging is the first for nAMD. FAF is a projection image that involves optical signal modulation by photoreceptors as well as emission signal sources in RPE. HyperFAF attributed to an exudative floodplain signifies loss of photoreceptors over continuous RPE. HypoFAF in MA signifies loss of both cell layers. FAF imaging should be interpreted with the multilayer perspective provided by OCT for maximal value. Prevention of exudation in nAMD may preserve photoreceptors.

PURPOSE/OBJECTIVE:To correlate structural changes of combined hamartoma of the retina and retinal pigment epithelium (CHRRPE) with patient age. DESIGN/METHODS:Retrospective study. SUBJECTS/METHODS:There were 50 eyes of 49 patients (age range 1-74 years) with CHRRPE studied at nine tertiary vitreoretinal institutions. METHODS:We analyzed the clinical findings with respect to lesion topography and pigmentation as well as investigated the optical coherence tomography (OCT) findings regarding the thickness, vitreoretinal interface, outer plexiform layer distortion, ellipsoid zone disruption and retinal pigment epithelium/Bruch's membrane complex involvement of CHRRPE. MAIN OUTCOMES/RESULTS:Clinical and imaging findings of CHRRPE at different ages. RESULTS:Analysis of 50 CHRRPE revealed younger patients were more likely to have partial thickness involvement of the retina (p = 0.009) with predominantly inner retinal layer involvement (p = 0.04). The inverse was true for older patients with CHRRPE. In addition, older patients more commonly showed pigmentary changes. Eyes with CHRRPE were more likely to have an increase in central macular thickness independently of tumor location. CONCLUSION/CONCLUSIONS:Based on these findings, we believe that CHRRPE typically begins in the inner retina and continues towards the outer retina over time, with increase in central macular thickness, despite the location of the tumor.

PURPOSE/OBJECTIVE:To describe the clinical and multimodal imaging (MMI) features of bacillary layer detachment (BD), and its response to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy, in eyes with macular neovascularization (MNV). DESIGN/METHODS:Retrospective, observational case series. METHODS:Fourteen eyes (14 patients, 7 male) were imaged with spectral-domain optical coherence tomography (OCT), and either fluorescein angiography or OCT angiography. Therapeutic response was monitored with serial imaging and best-corrected visual acuity (BCVA) assessments. RESULTS:Mean age was 75±13 (range: 45-96) years, with mean follow-up duration of 27±21 (range: 1-56) months. Neovascular age-related macular degeneration (nAMD) was found in 71% (10/14) eyes. Type 2 MNV lesions were associated with BD in all 14 eyes. Subretinal hemorrhage was noted in 79% (11/14) eyes. BD promptly resolved following intravitreal anti-VEGF therapy in all eyes. Baseline BCVA improved from LogMar 0.84±0.32 (Snellen equivalent 20/138) to LogMar 0.48±0.31 (Snellen equivalent 20/60) at last follow-up, with treatment of the MNV. CONCLUSIONS:Type 2 MNV and subretinal hemorrhage are associated with BDs, which may be due to a rapid influx of exudative fluid into the potential space between the external limiting membrane and ellipsoid zone. Intravitreal anti-VEGF therapy results in rapid resolution of BDs and visual improvement in most eyes.