Faculty Bibliography

PURPOSE/OBJECTIVE:To analyze the urinary metabolomic profile of central serous chorioretinopathy (CSC) cases. METHODS:In a cross-sectional study, 80 participants with CSC were compared with 80 age- and sex-matched controls. Urinary metabolites were measured using Metabolon's Discovery HD4TM platform. RESULTS:Of 1031 metabolites total that were measured in urine samples, 53 were up-regulated and 27 down-regulated in CSC participants compared with controls. After exclusion of potentially confounding xenobiotics and bile compounds that could represent digestive processes, 14 metabolites were significantly higher and 12 metabolites were significantly lower in cases compared with controls. One upregulated metabolite (tetrahydrocortisol sulfate) is involved in the corticosteroid sub-pathway. The down-regulated metabolites are unrelated to the identified corticosteroid sub-pathway. CONCLUSION/CONCLUSIONS:The upregulation of urinary tetrahydrocortisol sulfate in CSC cases provides a precise molecular basis to further study the role of corticosteroids in producing choroidal venous congestion.

PURPOSE/OBJECTIVE:To investigate whether non-invasive en face ultra-widefield (UWF) optical coherence tomography (OCT) can demonstrate salient features of the choroidal vasculature in eyes with central serous chorioretinopathy (CSC). DESIGN/METHODS:Retrospective observational case series. PARTICIPANTS/METHODS:Patients diagnosed with CSC who underwent UWF indocyanine green angiography (ICGA) and widefield OCT imaging were included. METHODS:Widefield OCT imaging was performed with a horizontal 23 mm x vertical 20 mm field of view of 5 visual fixations (1 central and 4 peripheral fixations) to compose structural en face UWF OCT montage images and UWF choroidal thickness maps. Automated image alignment was performed prior to grading. MAIN OUTCOME MEASURES/METHODS:A comparison of choroidal vascular findings seen with UWF ICGA and en face UWF OCT images including size and distribution of choroidal venous drainage areas and identification of dilated choroidal veins ("pachyvessels") crossing the physiological choroidal watershed zones. Spatial correlation between choroidal vascular hyperpermeability (CVH) on UWF ICGA images and areas of choroidal thickening (ACT) on UWF choroidal thickness maps was determined. RESULTS:Forty-two eyes from 27 CSC patients with a mean age of 56 ±12 years (range, 31 to 77 years) were included. Quantitative measures of vortex vein drainage areas on en face UWF OCT images were significantly and positively correlated with those obtained with UWF ICGA (mean Pearson r=0.825, P < 0.01). Identification of pachyvessels crossing the choroidal watershed zones showed an excellent correlation between UWF ICGA and en face UWF OCT images (mean Spearman ρ= 0.873, P < 0,01). In all cases, CVH observed on UWF ICGA spatially co-localized with ACT on the UWF choroidal thickness map. Congestion within the entire drainage area of the dominant vortex systems was observed on UWF choroidal thickness maps. CONCLUSIONS:In eyes with CSC, non-invasive en face UWF OCT imaging can show distinctive features of choroidal venous insufficiency previously identified with UWF ICGA. UWF OCT choroidal thickness maps enable quantitative assessment of choroidal congestion.

OBJECTIVES/OBJECTIVE:To explore the features of black hyperpigmentation in macular telangiectasia (MacTel) type 2 and correlate these findings with the characteristics of hyperpigmented epiretinal membranes (ERMs) using multimodal imaging. METHODS:A case series of three patients with MacTel type 2 and hyperpigmented ERMs imaged with colour fundus photography, fluorescein angiography (FA), spectral-domain optical coherence tomography (OCT) and swept-source OCT angiography. Registration of different types of imaging was done using ImageJ v1.53f51 (National Institutes of Health, USA). RESULTS:Three female patients with late-stage MacTel type 2 presented with unilateral hyperpigmented ERMs in the absence of peripheral retinal breaks. In one patient, an extensive ERM occurred along with a full-thickness macular hole (FTMH); in 2 patients, smaller ERMs were seen adjacent to superficial retinal veins. Serial imaging demonstrated that transretinal pigment migration preceded epiretinal proliferation of the hyperpigmented ERM towards superficial retinal veins. CONCLUSION/CONCLUSIONS:Hyperpigmented ERMs may occur in the late phases of MacTel type 2 following a FTMH or transretinal migration of pigmented cells to the retinal surface. Once on the retinal surface, black pigment cells seem to proliferate centripetally toward superficial retinal veins.

BACKGROUND:To evaluate whether the status of vasculature at the top of type 1 macular neovascularisation (MNV) could function as mediator of the observed protective effect against the development of complete retinal pigment epithelial and outer retinal atrophy (cRORA). METHODS:In consecutive treatment-naïve patients, the vasculature at the anterior surface of the MNV was isolated using a slab designed to extract the most superficial vascular portion of the MNV lesion showing a choriocapillaris (CC)-like structure which we termed the 'neo-CC'. The ratio between the neo-CC area (isolated using this custom slab) and the MNV area (isolated using the standard outer retina-CC slab) at baseline and at last follow-up was evaluated. RESULTS:Forty-four eyes from 44 patients were included. 20 showed cRORA by the final follow-up (median 23 months), whereas 24 did not progress to atrophy (median 23.5 months). The proportion of MNV with neo-CC at the anterior surface was significantly lower in eyes which progressed to cRORA compared with those which did not. The multivariate regression showed that a lower proportion of neo-CC coverage over the MNV was associated with an increased odds for cRORA development. CONCLUSIONS:More extensive coverage of neo-CC is associated with a lower likelihood of development of macular atrophy in eyes receiving antivascular endothelial growth factor therapy, suggesting the protective effect of a type 1 MNV may be mediated by the development of a neo-CC and may provide insights into the biological significance of MNV as a response mechanism in eyes with age-related macular degeneration.

OBJECTIVE:To characterize the multimodal retinal findings of myopic macular pits, a feature of myopic degeneration. METHODS:A case series of patients with myopic macular pits were studied with multimodal imaging including color fundus photography, fundus autofluorescence (FAF), near infrared reflectance (NIR), spectral domain optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), fluorescein angiography (FA) and indocyanine green angiography (ICG). RESULTS:Nine eyes of 6 patients with myopic macular pit were examined. Four patients presented with multiple pits and 3 with bilateral involvement. All pits were localized in a region of severe macular chorioretinal atrophy associated with myopic posterior staphyloma. In 3 eyes, the entrance of the posterior ciliary artery through the sclera was noted at the base of the pit. Schisis overlying the pit or adjacent to the pit was identified in 3 patients. CONCLUSION/CONCLUSIONS:Myopic macular pits are an additional rare sign of myopic degeneration, developing in regions of posterior staphyloma complicated by severe chorioretinal atrophy and thin sclera.

PURPOSE/OBJECTIVE:To report a case of Vogt-Koyanagi-Harada (VKH)-like uveitis followed by melanoma-associated retinopathy (MAR) with focal chorioretinal atrophy and subsequent choroidal neovascularization (CNV) in a patient with metastatic cutaneous melanoma. OBSERVATION/METHODS:A 68-year-old man with a history cutaneous melanoma presented with VKH-like uveitis. Work up revealed a pelvic mass, which was excised and found to be metastatic melanoma. Two years later, the patient developed MAR with focal chorioretinal atrophy and adjacent CNV. CONCLUSION/CONCLUSIONS:and Importance: Patients with metastatic cutaneous melanoma can develop distinct and sequential paraneoplastic ocular complications. Onset of a VKH-like uveitis may be a good prognostic factor for survival in patients with metastatic cutaneous melanoma.

PURPOSE/UNASSIGNED:To describe delayed detection of pericentral hydroxychloroquine (HCQ) toxicity. METHODS/UNASSIGNED:67-year-old Dominican woman with rheumatoid arthritis on HCQ presented for examination. RESULTS/UNASSIGNED:Spectral-domain optical coherence tomography (SD-OCT) demonstrated bilateral cystoid macular edema with parafoveal attenuation of the external limiting membrane (ELM) and the ellipsoid zone (EZ). ELM and EZ disruption was present in inferior macula. While subtle superior defects were present on 10-2 visual fields, superior pericentral defects were noted on 24-2 testing. Hyperautofluorescence along inferior arcades corresponded to SD-OCT and visual fields. Examination 2 years prior demonstrated nonspecific points of depression on 10-2 visual fields and normal central SD-OCT findings. EZ and ELM disruption was present in the perifoveal inferior macula. CONCLUSIONS/UNASSIGNED:Early pericentral distribution of HCQ toxicity is not limited to Asian patients. Detecting pericentral HCQ toxicity involves reviewing entire macular cube on OCT. When OCT changes are suspected on parafoveal OCT B-scans, visual field testing with 24-2 may be more sensitive than 10-2.

Background/aims Demonstrate that subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are linked to coexistent high-risk vascular diseases (HRVDs). Methods Cross-sectional study. Two hundred AMD subjects (aged 51-100 years; 121 women, 79 men) were recruited. Spectral domain optical coherence tomography, autofluorescence and near-infrared reflectance imaging, and lipid profiles were obtained. Subjects were assigned by health history questionnaires into those with or without HRVDs, defined as: cardiac valve defect (eg, aortic stenosis), myocardial defect (eg, myocardial infarction) and stroke/transient ischaemic attack. Masked readers assigned subjects into two groups: SDD (with or without drusen) and drusen (only). Univariate testing was performed by χ 2 test. We built multivariate regression models to test relationships of coexistent HRVD to SDD status, lipid levels and other covariates. Results The prevalence of HRVD was 41.2% (40/97) and 6.8% (7/103) in the SDD and non-SDD groups, respectively (correlation of SDD with HRVD, p=9×10 -9, OR 9.62, 95% CI 4.04 to 22.91). Multivariate regressions: only SDDs and high-density lipoprotein (HDL) in the first two HDL quartiles remained significant for HRVD (p=9.8×10 -5, 0.021, respectively). Multivariate regression model: SDDs and an HDL in Q1 or Q2 identified the presence of HRVD with the accuracy of 78.5%, 95% CI 72.2% to 84.0%. Conclusions High-risk cardiovascular and neurovascular diseases were accurately identified in an AMD cohort from SDDs and HDL levels. The SDDs may be related to inadequate ocular perfusion resulting from the systemic vasculopathies. Further research with this paradigm is warranted and might reduce mortality and morbidity from vascular disease.