Faculty Bibliography

Many retinal diseases and imaging findings have pathophysiologic underpinnings in the function of the cardiovascular system. Myriad retinal conditions, new imaging biomarkers, and novel image analysis techniques have been investigated for their association with future cardiovascular risk or utility in cardiovascular risk prognostication. An intensive literature search was performed to identify relevant articles indexed in PubMed, Scopus, and Google Scholar for a targeted narrative review. This review investigates the literature on specific retinal disease states, such as retinal arterial and venous occlusions and cotton wool spots, that portend significantly increased risk of future cardiovascular events, such as stroke or myocardial infarction, and the implications for personalized patient counseling. Furthermore, conditions diagnosed primarily through retinal bioimaging, such as paracentral acute middle maculopathy and the newly discovered entity known as a retinal ischemic perivascular lesion, may be associated with future incident cardiovascular morbidity and are also discussed. As ever-more-sophisticated imaging biomarkers and analysis techniques are developed, the review concludes with a focused analysis of optical coherence tomography and optical coherence tomography angiography biomarkers under investigation for potential value in prognostication and personalized therapy in cardiovascular disease.

PURPOSE:To assess the association of a novel spectral domain optical coherence tomography biomarker with 6-month visual acuity in in the Study of COmparative Treatments for REtinal Vein Occlusion 2. METHODS:Spectral domain optical coherence tomography volume scans were evaluated for inner retinal hyperreflectivity, quantified by optical intensity ratio (OIR) and OIR variation. Baseline visual acuity letter score (VALS), baseline OCT biomarkers, and month 1 OIR were correlated with VALS at month 6. Regression trees, a machine learning technique yielding readily interpretable models, were used to assess for variable interaction. RESULTS:Only baseline VALS correlated positively with month 6 VALS in multivariate regression. Regression trees detected a novel functional and anatomical interaction in a subgroup. Among patients with a baseline VALS worse than 43, those with an OIR variation at month 1 of more than 0.09 had a mean of 13 fewer letters of vision at 6 months compared with patients with an OIR variation of 0.09 or less. CONCLUSIONS:Baseline VALS was the strongest predictor of month 6 VALS. Regression tree analysis detected an interaction effect, in which higher OIR variation at month 1 predicted worse 6-month VALS in patients with low VALS at baseline. OIR variation may serve as a predictor for poor visual outcome despite treatment of macular edema secondary to retinal vein occlusion in patients with poor vision at baseline. TRANSLATIONAL RELEVANCE:Pixel heterogeneity in three-dimensional OCT data may serve as measure of disruption of the retinal laminations, and this factor may carry visually prognostic value.

OBJECTIVES/OBJECTIVE:To determine the relationship between treatment frequency with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents and visual acuity (VA) outcomes in eyes with macular oedema (MO) secondary to branch retinal vein occlusion (BRVO) in US clinical practice. METHODS:Study eyes that initiated anti-VEGF injections between January 2012 and May 2016 were followed for ≥1 year in a retrospective analysis of medical records (Vestrum Health database). Eyes were analysed in 2 cohorts by treatment duration (years 1 and 2) and then in 2 subcohorts by injection frequency (≤6 or ≥7 injections/year). RESULTS:Among 3099 eyes with MO secondary to BRVO, 1197 (38.6%) received ≤6 injections (mean injections, 4.6; baseline mean VA, 53 letters) and 1902 (61.4%) received ≥7 injections through 1 year (mean injections, 8.8; baseline mean VA, 52 letters). At year 1, mean VA gain from baseline was 10.4 versus 13.9 letters in eyes receiving ≤6 versus ≥7 injections (p < 0.001). At year 2, mean VA in eyes receiving ≤6 (n = 42) versus ≥7 injections (n = 227) was 64 versus 68 letters, respectively (p = 0.19). Mean VA change between the start and end of year 2 in eyes receiving ≥7 injections in year 1 and ≤6 in year 2 differed significantly from that of eyes receiving ≥7 injections in both years (-3.0 vs 0.7 letters, respectively; p < 0.001). CONCLUSIONS:In routine clinical practice, more frequent dosing with anti-VEGF agents was associated with greater visual benefits in eyes with MO secondary to BRVO.

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.

PURPOSE/UNASSIGNED:To describe a rare case of intraocular lymphoma that metastasized from cutaneous mycosis fungoides and transformed to large cell T cell lymphoma resulting in vitreoretinal pathology. METHODS/UNASSIGNED:Retrospective case report. RESULTS/UNASSIGNED:A 57-year-old male presented with 3 months of blurred vision in the right eye. He reported only a medical history of psoriasis. Examination revealed keratic precipitates and dense vitritis in the right eye. He was taken for a diagnostic vitrectomy. Histopathology showed that atypical lymphoid cells and flow cytometry were consistent with transformed large cell T-cell lymphoma. During follow-up, pre- and inner retinal lesions were noted throughout the posterior pole. Histopathology of the psoriatic lesions was consistent with mycosis fungoides. He was initiated on systemic and intravitreal methotrexate with improvement in vision. CONCLUSIONS/UNASSIGNED:Ocular involvement in metastatic transformed T-cell lymphoma is extremely rare but can be present with vitritis and retinal deposits. Our patient responded well to intravitreal methotrexate therapy.

Purpose : To evaluate the diagnostic yield and clinical impact of the SPARK/Invitae gene panel in patients with known or suspected inherited degenerative retinal disease, in comparison with traditional clinical assessments. Methods : Patients of the authors' clinical practices obtained genetic screening at no charge via the SPARK/Invitae ID your IRD genetic testing panel, which ranged from 248 genes to 293 genes. Over 16 months, tests were submitted for 87 patients and results were available for 70 patients. Clinical diagnoses prior to submitting the gene panel . By continuing to use our website, you are agreeing to included retinitis pigmentosa; Stargardt disease; Best vitelliform dystrophy; Leber our privacy policy. congenital amaurosis; choroideremia; achromatopsia; cone-rod dystrophy; congenital stationary night blindness; occult macular dystrophy; and familial dominant drusen in addition to patients with normal clinical findings and unclear diagnoses. Results : Of 70 patients, SPARK/Invitae considered the results ''Positive or Potentially Positive'' in 24 cases (34.3%), Carrier in 16 cases (22.9%) and ''Uncertain'' in 30 cases (42.9%). Uncertain results comprised patients with only Variants of Uncertain Significance. Patients categorized as a Carrier by SPARK/Invitae but who demonstrated pathogenic genetic changes correlating to the clinical diagnosis were considered to be in agreement with the clinical impression. The genetic diagnosis agreed with the clinical diagnosis in 30/70 (42.9%) total patients. Test results were consistent with the clinical impression in 13/26 (50.0%) retinitis pigmentosa cases, 6/8 (75.0%) Stargardt patients, 3/7 (42.9%) cone-rod dystrophy cases, and 2/4 (50.0%) Best vitelliform dystrophy patients. Gene testing helped elucidate diagnoses in two patients with unclear clinical impressions: one panel showed autosomal recessive achromatopsia and the other showed a carrier state for autosomal recessive retinitis pigmentosa. Of four patients with normal clinical exams, none had diagnostic results: all showed Uncertain findings. Conclusions : The SPARK/Invitae gene panel provided a genetic diagnosis consistent with the clinical impression in about 40 percent of patients. Retinitis pigmentosa and Stargardt disease were the most common clinical diagnoses and the diagnoses most often confirmed by testing. Genetic screening also assisted in clarifying unknown diagnoses for two patients

Purpose/UNASSIGNED:The purpose was to establish the position of the fovea centralis to the optic nerve via en-face, near-infrared spectral domain optical coherence tomography (NIR-OCT) in healthy patients. This may shed light on physiological variability and be used for studying subtle cases of foveal ectopia in macular pathology and after retinal detachment. Methods/UNASSIGNED:SD-OCT data of 890 healthy eyes were retrospectively analyzed. Exclusion criteria included axial myopia causing tilting of the optic disc, peripapillary atrophy >1/3 the width of the disc, macular images excluding greater than half of the optic disc, and patients unable to maintain vertical head positioning. Two independent reviewers measured the horizontal and vertical distance from the fovea to the optic disc center and optic disc diameter via cross-sectional and en-face scanning laser ophthalmoloscopy OCT imaging. Results/UNASSIGNED:890 eyes were included in the study. The right and left eyes differed in the horizontal distance from the fovea to the disc center (4359 vs. 4248 µm, P < 0.001) and vertical distance from the fovea to the disc center (464 µm vs. 647, P < 0.001). This corresponded to a smaller angle between the right and left eyes (6.07° vs. 8.67°, P < 0.001). Older age was associated with a larger horizontal (P = 0.008) and vertical distance (0.025). These differences persisted after correcting for axial length in the 487 patients with axial-length data. Conclusions/UNASSIGNED:This study compares the position of the fovea centralis among individuals without macular pathology on a micron level basis. The significant variability between right and left eyes indicates that contralateral eye evaluation cannot be reliably used. Rather, true foveal ectopia requires assessments of preoperative and postoperative NIR-OCT scans. This finding is relevant to retinal detachment cases and evaluation of subtle foveal ectopia. Translational Relevance/UNASSIGNED:This finding is relevant to retinal detachment cases and evaluation of subtle foveal ectopia.