RELATIONSHIP BETWEEN CHOROIDAL VASCULAR HYPERPERMEABILITY, CHORIOCAPILLARIS FLOW DENSITY, AND CHOROIDAL THICKNESS IN EYES WITH PACHYCHOROID PIGMENT EPITHELIOPATHY.

PURPOSE: 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: Reduced choriocapillaris flow density, increased choroidal thickness, and CVH appear to co-localize in eyes with pachychoroid pigment epitheliopathy.

Utility of en-face imaging in diagnosis of occult macular dystrophy with RP1L1 mutation: A case series.

PURPOSE: To report en-face imaging findings at the level of ellipsoid zone (EZ) in two cases of occult macular dystrophy (OMD) with retinitis pigmentosa 1-like 1 (RP1L1) p.Arg45Trp mutation. OBSERVATIONS: In both patients who presented with decreased vision, pupillary examination, intraocular pressure, and anterior examination were normal. Ophthalmoscopic examination showed prominent choroidal marking whereas fundus autofluorescence was unremarkable. Spectral domain optical coherence tomography (SD-OCT) showed subtle gaps between EZ and retinal pigment epithelium (RPE). The photoreceptor disruption became more evident with en-face imaging at the EZ plane. CONCLUSIONS AND IMPORTANCE: This is a report of two patients with EZ en-face imaging that aided in the diagnosis of OMD where other structural imaging was largely unremarkable. The en-face imaging modality can also be used to monitor OMD progression.

Schisis of the Retinal Nerve Fiber Layer in Epiretinal Membranes.

PURPOSE: To describe schisis of the retinal nerve fiber layer (sRNFL) associated with epiretinal membranes (ERMs) seen on spectral-domain optical coherence tomography (OCT) prior to vitreoretinal surgery. Areas of sRNFL (size and location) were noted during preoperative planning. Spectral-domain OCT scans were obtained to study the inner retinal morphology postoperatively. DESIGN: Retrospective observational consecutive case series. METHODS: Pre- and postoperative spectral-domain OCT and en face images of 41 eyes with ERMs that had undergone vitrectomy by a single surgeon were analyzed to record the presence of sRNFL. The extent of sRNFL was classified as focal or diffuse. Other characteristics such as involvement of the papillomacular bundle and areas of fibrillary protrusion of sRNFL above the internal limiting membrane (ILM) were documented. Color fundus photographs were reviewed to correlate with the spectral-domain OCT images. RESULTS: Mean patient age and length of follow-up were 69.3 years (range 52-82 years) and 6.8 months (range 0.25-21 months), respectively. Mean preoperative and postoperative central thicknesses were 477 µm and 387 µm, respectively (P < .0001). sRNFL was observed in 51.2% (21/41 eyes), and was classified as diffuse (>1 disc diameter) in 90.5% (19/21 eyes). Protrusion of sRNFL through the ILM was present in 76.2% (16/21 eyes) and occurred in areas of dehiscence of the adjacent ILM. sRNFL was best visualized on spectral-domain OCT and en face imaging at the vitreoretinal interface and sometimes correlated with areas of retinal whitening. sRNFL resolved in all cases postoperatively. CONCLUSIONS: sRNFL was a relatively common occurrence in ERMs, correlated frequently with areas of dehisced ILM intraoperatively, and resolved postoperatively in all cases.

Hemoglobin level and macular thinning in sickle cell disease.

Purpose: To study the relationship between complete blood count (CBC) indices over time, particularly serum hemoglobin (Hb) levels, and severity of macular thinning on spectral domain optical coherence tomography (SD-OCT) in patients with sickle cell disease (SCD). Methods: This is a single-center, retrospective analysis of 141 consecutive SCD patients over a 10-year period, of which 40 patients (79 eyes) had SD-OCT imaging of the macula and 29 (58 eyes, mean age 17.5 years) were eligible for the study. Investigators reviewed electronic medical records for documentation of retinopathy stage, disease genotype, CBC values, and SD-OCT imaging. SD-OCT parameters and CBC values were compared between different retinopathy stages and disease genotypes. Regression analyses were performed on SD-OCT parameters and CBC values. Results: Of the 58 eligible eyes (34HbSS, 18HbSC, 4HbSß +thal, 2HbS ßthal), 18 had PSR (proliferative sickle retinopathy), 14 had NPSR (nonproliferative sickle retinopathy), and 26 had NSR (no sickle retinopathy). Hb values were higher in SC group compared to SS group. Macular thickness in the temporal inner (Δ=26±33 um, p=0.01) and outer (Δ=21±30 um, p=0.02) subfields was higher in SC compared to SS group. Patients with SD-OCT thinning below the 5th percentile in the temporal outer subfields had lower recorded Hb nadirs (6.0±0.9) compared to those with thickness within the top 95th percentile (9.1±2.3). Regression analysis showed temporal macular thickness to be positively correlated with Hb values in the SS group. Conclusion: Macular thinning observed on SD-OCT in SCD patients with SS genotype may be related to the level of anemia in this population.

Multimodal Imaging of Atypical Acute Syphilitic Posterior Placoid Chorioretinitis Mimicking a White Dot Syndrome.

As rates of infectious syphilis continue to rise in the U.S., it is important to be familiar with known manifestations of ocular syphilis as well as report presentations not previously described in the literature. Here, the authors report a case of a 49-year-old myopic woman presenting with bilateral white dots characteristic of a white dot syndrome; these white dots were not evident on slit-lamp examination and became obvious on fundus autofluorescence. She tested positive and was successfully treated for syphilis. This case demonstrates that ocular syphilis can present with white dots and should be on the differential diagnosis of white dot syndromes. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e52-e55.].

SPECKLED HYPOAUTOFLUORESCENCE AS A SIGN OF RESOLVED SUBRETINAL HEMORRHAGE IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To describe patterns of hypoautofluorescence in eyes with neovascular age-related macular degeneration occurring after subretinal hemorrhage. METHODS: This was a retrospective descriptive analysis of neovascular age-related macular degeneration eyes presenting with subretinal hemorrhage over the last 5 years that underwent serial multimodal imaging. A review of color fundus photographs, fundus autofluorescence, near-infrared reflectance, and optical coherence tomography was performed at baseline and all available follow-up visits to document the course and evolution of subretinal hemorrhage in these eyes. RESULTS: Eleven eyes of 10 patients (9 female, 1 male; mean age: 84.1 years, range: 72-99 years) with a mean follow-up of 19.8 months (range: 3-68 months) were included. Color fundus photographs showed subretinal hemorrhage that resolved over a mean of 5.5 months. During and after hemorrhage resolution, all eyes showed hypoautofluorescence, which appeared distinct from that due to retinal pigment epithelium loss. Discrete multifocal punctate hyperpigmented lesions were observed in 90% of eyes and were markedly hypoautofluorescent, producing a speckled pattern on fundus autofluorescence. CONCLUSION: Areas of hypoautofluorescence in the absence of retinal pigment epithelium atrophy, often with a speckled pattern, delineate areas of prior subretinal hemorrhage long after its resolution in patients with neovascular age-related macular degeneration. Potential mechanisms for the development of this pattern are proposed.

CD44posCD49fhiCD133/2hi defines xenograft-initiating cells in estrogen receptor-negative breast cancer.

Defining the populations of tumor-initating cells that are present in tumors is a first step in developing therapeutics to target these cells. We show here that both CD44(pos)CD24(neg) and CD44(pos)CD24(pos) cell populations in estrogen receptor (ER) alpha-negative breast tumors are tumorigenic in murine xenograft models. We also describe a third population of xenograft-initiating cells (XIC) enriched in CD44(pos)CD49f(hi)CD133/2(hi) cells that display heightened tumorigenicity, self-renewal in vivo, and the capacity to give rise to functional and molecular heterogeneity. Consistent with their capacity for self-renewal, these cells express elevated levels of Sox2, Bmi-1, and/or Nanog and their CpG islands are hypermethylated relative to nontumorigenic cells. These differences in methylome regulation may be responsible for the dramatic functional differences between the two populations. The identification of CD44(pos)CD49f(hi)CD133/2(hi) XIC in ER-negative tumors may lead to expanded understanding of these tumors and ultimately the development of therapeutics designed to specifically target the cells.