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Determining Choroidal Vascular Density Using En Face SS-OCT

Scientists quantified the vascular density of the choroid of normal eyes and identified the influencing factors using en face images obtained with swept-source optical coherence tomography, in a prospective, cross-sectional study.

They analyzed 163 eyes of 163 healthy volunteers (83 female; mean age 42.2 ±22.6 years) with a corrected visual acuity of ≥1 (Snellen equivalent: 20/20 or better). They used en face SS-OCT images of the choroid for quantitative assessment of the vascular density in the large choroid vessel layer. They also assessed relationships between vascular density of the choroid and age, sex, refractive error, axial length and subfoveal choroidal thickness.

Scientists uncovered a significant negative relationship between vascular density of the choroid and subject age (p<0.001). Analysis according to age showed a significant correlation in the group older than 30 years (p<0.001), but not in the group ≤30 years (p=0.225). SCT had a significant positive relationship with vascular density of the choroid (p<0.001). However, a significant correlation was not observed between vascular density of the choroid and sex (p= 0.981), RE (p=0.292) or AL (p=0.216). Multi-variable regression analysis with vascular density of the choroid as the dependent variable, and age, sex, RE, AL and SCT as independent variables showed that age and SCT are important determinants of vascular density of the choroid (p<0.001).

Scientists concluded that age and SCT affected vascular density of the choroid.

SOURCE: Fujiwara A, Morizane Y, Hosokawa M, et al. Factors affecting choroidal vascular density in normal eyes: Quantification using en face swept-source optical coherence tomography. Am J Ophthalmol 2016; July 15. [Epub ahead of print].

Increased Choroidal Vascularity in CSC Quantified Using SS-OCT

Investigators assessed the choroidal vascular structural changes in eyes with central serous chorioretinopathy by using swept-source optical coherence tomography, as part of a prospective, cross-sectional study.

They prospectively examined 40 eyes of 34 consecutive individuals with CSC, and obtained three-dimensional choroidal images of the macular area, covering 3 × 3 mm and 6 × 6 mm, with SS-OCT. They converted en face images of the inner choroid and large choroidal vessel layer microvasculature to binary images, and quantitatively analyzed choroidal vascular areas.

The choroidal vascular area was larger in eyes with CSC. The microvasculature of the inner choroid was: 53.4 ±2.4 percent, p=0.028, compared with 52.2 ±1.8 percent in age-matched normal eyes; 3 × 3-mm large choroidal vessels: 66.9 ±7.1 percent, p<0.001, compared with 54.9 ±4.4 percent in age-matched normal eyes; and 6 × 6-mm large choroidal vessels: 64.8 ±7.3 percent, p<0.001, compared with 53.8 ±4.3 percent in age-matched normal eyes. The choroidal vascular area at the microvasculature of the inner choroid level was larger in multifocal posterior pigment epitheliopathy (55.8 ±2.2 percent) than in classic CSC (53.1 ±2.1 percent, p=0.038) and in diffuse retinal pigment epitheliopathy (52.9 ±2.6 percent, p=0.042). Subfoveal choroidal thickness was significantly associated with the choroidal vascular area at the level of large choroidal vessels (p<.001).

Investigators observed increased choroidal vascular area in the whole macular area in eyes with CSC, which they wrote suggests that CSC may originate from a choroidal circulatory disturbance.

SOURCE: Kuroda Y, Ooto S, Yamashiro K, et al. Increased choroidal cascularity in central serous chorioretinopathy quantified using swept-source optical coherence tomography. Am J Ophthalmol 2016; July 6 [Epub ahead of print].

Repeatability of Automated Vessel Density Measurements Using OCTA

Researchers determined the repeatability of optical coherence tomography angiography-derived automated vessel density measurements in the superficial retinal layer and deep retinal layer in healthy individuals.

Forty-one eyes of 21 healthy individuals were included in the study in which researchers performed OCTA using the NIDEK RS-3000 Advance with prototype OCTA software. Each subject underwent two scanning sessions with five to 10 minutes between. They generated en face images of the retinal vasculature using the default segmentation for SRL and DRL, and compared automated vessel density measurements between the two sessions. They used intraclass correlation coefficients and coefficient of repeatability as measures for repeatability.

The mean ±SD age of the subjects was 36.8 ±7.5 years. Overall vessel density measured was 19.43 ±3.10 in the first session and 19.72 ±3.78 in the second session for the SRL, and 34.67 ±1.801 in the first session and 34.55 ±1.64 in the second session for the DRL. The mean difference in vessel density between sessions was -0.3 (95 percent CI 3.3 to -3.9) for the SRL and 0.1 (95 percent CI 2.6 to -2.5) for the DRL. The two measurements were highly correlated with an ICC=0.9 (p=0.33) for the SRL and 0.83 (p=0.589) for the DRL. The coefficient of variation was 0.052 for the SRL and 0.02 for the DRL.

Researchers wrote that commercial automated vessel density measurements using OCTA showed excellent repeatability in healthy individuals. Although they added that repeatability would need to be established in the setting of disease, researchers indicated that the existing level of reproducibility should be useful for assessing the significance of differences in capillary density over time or under different conditions.

SOURCE: Al-Sheikh M, Tepelus TC, Nazikyan T, et al. Repeatability of automated vessel density measurements using optical coherence tomography angiography. Br J Ophthalmol 2016; July 26. [Epub ahead of print].

Image Artifacts in SS-OCTA

Researchers described optical coherence tomography angiography image artifacts in eyes with and without ocular pathologies by retrospectively reviewing the OCTA images of healthy subjects and individuals with age-related macular degeneration, diabetic retinopathy and retinal vascular occlusions.

Researchers used a swept-source OCTA instrument (Triton, Topcon) to obtain OCTA images. They assessed the frequency of various image artifacts including: segmentation; banding; motion; projection; masking; unmasking; doubling of the retinal vessels; blink; stretching; and out-of-window and crisscross artifacts. They evaluated the artifact’s impact on image grading for the foveal avascular zone in deep and superficial retinal layers, capillary non-perfusion and choroidal neovascularization.

The OCTA images were of 57 eyes of 48 subjects, including 23 eyes (40.3 percent) with CNV, 13 eyes (22.8 percent) with dry age-related macular degeneration, nine eyes (15.7 percent) with cystoid macular edema due to diabetic retinopathy or retinal vein occlusion, and 12 normal eyes (21.1 percent). At least one type of artifact was present in the images of 51 eyes (89.4 percent). The rates of occurrence were:

• banding artifacts: 51 eyes (89.4 percent);
• segmentation: 35 eyes (61.4 percent);
• motion: 28 eyes (49.1 percent);
• unmasking: nine eyes (15.8 percent);
• blink: five eyes (8.8 percent);
• vessel doubling: one (1.7 percent);
• masking:one eye (1.7 percent); and
• out-of-window artifacts: one eye (1.7 percent).

SS-OCT Findings in Early HCQ Retinopathy Detection & Changes After Drug Cessation

Researchers wrote that expanded SD-OCT findings of HCQ retinopathy may assist clinicians in earlier diagnosis. They aimed to characterize structural changes of HCQ retinopathy with SD-OCT after drug cessation.

Individuals seen at New England Eye Center and Ophthalmic Consultants of Boston, who had been diagnosed with HCQ retinopathy and followed after drug cessation, were included in the retrospective clinical data review by the Boston Image Reading Center.

Main outcome measures were SD-OCT findings suggestive of HCQ retinopathy before parafoveal ellipsoid disruption, and change in SD-OCT morphological appearance and retinal thickness relative to each of the nine subfields corresponding to the Early Treatment of Diabetic Retinopathy Study areas.

Using SD-OCT, researchers followed 30 eyes with HCQ retinopathy after drug cessation. Findings before disruption of the parafoveal EZ included parafoveal outer nuclear layer thinning, disruption of the parafoveal interdigitation zone and reduced reflectivity of the parafoveal EZ. In early toxicity, 75 percent of individuals developed progression after drug cessation, including disruption of the parafoveal EZ and retinal pigment epithelium, and thinning of the ONL. Eyes with obvious toxicity had greater inferior outer ring thinning 12 months after drug cessation compared with early toxicity (p=0.002; 95 percent CI −2 to −8 μm). In obvious toxicity, the nasal inner subfield showed more thinning than the temporal inner subfield at 12 months after drug cessation (p=0.018; 95 percent CI −1 to −8 μm).

Researchers concluded that once HCQ retinopathy was diagnosed and medication was discontinued, structural retinal changes commonly occurred.

SOURCE: Lally DR, Heier JS, Baumal C, et al. Expanded spectral domain-OCT findings in the early detection of hydroxychloroquine retinopathy and changes following drug cessation. J Ret Vit Dis 2016;July 8 [Epub ahead of print].

Intravitreal Aflibercept Treatment in DME: VIVID-DME and VISTA-DME Data

Researchers wrote that diabetic macular edema shows a gradual and sustained functional and morphologic response to anti-vascular endothelial growth factor drugs, but that the optimal schedule for initiation of anti-VEGF therapy is not known. They evaluated the treatment response behavior of DME in the Phase III trials of intravitreal aflibercept, with five initial intravitreal aflibercept injections (IAI), 2 mg every four weeks (2q4), in the upload phase. The researchers are consultants for, or have received honoraria, from Bayer and/or Regeneron.

The post hoc pooled analysis of the VISTA-DME (NCT01363440) and VIVID-DME (NCT01331681) trial evaluated the change in best-corrected visual acuity and central retinal thickness during the upload phase, using pooled data from both IAI treatment groups [2q4 and 2 mg every eight weeks (2q8)]. Researchers calculated mean visit-to-visit changes in BCVA and CRT, and the respective rate of gainers and losers for each successive visit. A secondary analysis compared the visit-to-visit change in BCVA between the 2q4 and 2q8 treatment arms during the upload period and the first year treatment period.

The majority of eyes showed continuing BCVA improvement after the first IAI. The proportions of eyes gaining BCVA (≥5 letters) at each visit compared with the previous visit during the IAI 2q4 upload phase were 60 percent (four weeks), 19 percent (eight weeks), 16 percent (12 weeks), 15 percent (16 weeks) and 14 percent (20 weeks). In contrast, the proportion of eyes losing BCVA (≥5 letters) were 3 percent (4 weeks), 7 percent (eight weeks), 7 percent (12 weeks), 9 percent (16 weeks) and 8 percent (20 weeks), respectively. The odds of BCVA (≥5 letters) gain/loss exceeded 1.7 at each visit (range 1.7 to 20). Overall, the proportion of individuals with BCVA gain ≥5 letters at week 20 (compared with baseline) was 76 percent in the 2q4 group and 80 percent in the 2q8 group. The proportions of eyes showing a visit-to-visit decrease in CRT ≥30 µm during the first five IAIs were 77 percent (four weeks), 27 (eight weeks), 21 percent (12 weeks), 17 (16 weeks) and 12 percent (20 weeks). In the secondary analysis, BCVA outcomes were similar for the 2q8 and 2q4 treatment arms.

Researchers concluded that data were consistent with continual functional and anatomic improvement following the fourth and fifth initial 2q4 injections, suggesting an intensive and sufficiently long upload could be beneficial.

SOURCE: Ziemssen F, Schlottman PG, Lim JI, et al. Initiation of intravitreal aflibercept injection treatment in patients with diabetic macular edema: A review of VIVID-DME and VISTA-DME data. J Ret Vit Dis 2016 July 11 [Epub ahead of print].

Relationship of Renal & Vascular Function Markers With Retinal Blood Vessel Response

Investigators looked at the possibility of a significant relationship between systemic markers of renal and vascular function, and retinal microvascular function, in diabetes and/or cardiovascular disease.

They measured ocular microcirculatory function in 116 subjects with diabetes and/or cardiovascular disease using static and continuous retinal vessel responses to three cycles of flickering light. They then evaluated endothelial function by von Willebrand factor, endothelial microparticles and soluble E selectin; and renal function by serum creatinine, creatinine clearance and estimated glomerular filtration rate. They used HbA1c as a control index.

Central retinal vein equivalence and venous maximum dilation to flicker were linked to HbA1c (both p<0.05); arterial reaction time was linked to serum creatinine (p=0.036) and eGFR (p=0.039); venous reaction time was linked to creatinine clearance (p=0.018); and creatinine clearance and eGFR were connected to arterial maximum dilatation (p<0.001 and p=0.003, respectively) and dilatation amplitude (p=0.038 and p=0.048, respectively) in the third flicker cycle.

Among venous responses to the first flicker cycle, HbA1c was linked to the maximum dilation response (p=0.004) and dilatation amplitude (p=0.017); vWf was linked to maximum constriction response (p=0.016); and creatinine clearance showed a connection with baseline diameter fluctuation (p=0.029). In the second flicker cycle, dilatation amplitude was linked to serum creatinine (p=0.022).

Investigators found that several retinal blood vessel responses to flickering light were linked to glycemia and renal function, but only one index was linked to endothelial function. As such, they said renal function must be considered when interpreting retinal vessel responses.

SOURCE: Heitmar R, Varma C, De P, et al. The relationship of systemic markers of renal function and vascular function with retinal blood vessel responses. Graefe’s Arch Clin Exp Ophthalmol 2016; July 20. [Epub ahead of print].

Fundus Photography to Screen for Diabetic Retinopathy in Type 1 Diabetes

Investigators determined the success rate of initial fundus photography in producing gradable images for screening diabetic retinopathy in children older than 18 years of age with type 1 diabetes, and analyzed outcome-associated factors in a retrospective, observational study.

Investigators graded mydriatic, red-free, monochromatic, 60-degree digital fundus images centered on the macula and optic disc of 213 individuals. Photography success was classified as "complete" (both images of both eyes were gradable); "partial" (both images of one eye were gradable); "macula-centered image(s) only"; and "unsuccessful" (neither macula-centered image was gradable).

Complete success was reached in 97 individuals (46 percent; 95 percent CI, 39 to 52); partial success in 153 people (72 percent; 95 percent CI, 65 to 78) and success of macula centered image(s) in 47 individuals (22 percent; 95 percent CI, 17-28); with fundus photography unsuccessful in 13 people (6 percent; 95 percent CI, 3 to 10). Macula-centered images were more often gradable in both eyes than optic disc-centered images (p<0.001). Success did not differ between right and left eyes. Factors including gender, age at diagnosis of type 1 diabetes, and duration of diabetes and glycemic control at initial photography weren’t associated with complete success. Partial success tended to decrease with increasing age (p=0.093), and the frequency of gradable macula-centered image(s) increased with advancing age (p=0.043).

Investigators found that less than half of the children achieved complete success, and in only 6 percent, initial fundus photography was unsuccessful, which investigators suggested demonstrated its value in assessing retinopathy in the pediatric setting.

SOURCE: Gräsbeck TC, Gräsbeck SV, Miettinen PJ, et al. Fundus photography as a screening method for diabetic retinopathy in children with type 1 diabetes: Outcome of the initial photography. Am J Ophthalmol 2016; July 4. [Epub ahead of print].

GA Using Color Photographs and Fundus Autofluorescence Images

Researchers compared area of geographic atrophy and change in GA area on color photographs and fundus autofluorescence images. The Age-Related Eye Disease Study 2 prospective, multicenter, randomized clinical trial evaluated progression of dry age-related macular degeneration using color photographs at annual visits over a five-year study period. FAF images were acquired in a subset of participants who joined an ancillary study at an annual visit over the study period.

The AREDS2 FAF ancillary study included 8,070 visits to take the corresponding color and FAF images of 2,202 participants with variable follow-up. The images were independently evaluated at a central reading center for GA area measurement, lesion growth and macula center involvement.

Main outcome measures included presence, area, GA growth rate and macular center involvement, utilizing color and FAF images.

Hypoautofluorescence was visible in 2,048 visits (25.4 percent). Agreement for GA presence between the two modalities had a kappa of 0.79, with 23 percent of visits with hypoautofluorescence not presenting with GA on color photographs. Percentage agreement for GA presence ranged from 43 percent at baseline to 81 percent at year five, with improving agreement over time. The mean difference in GA area between the two modalities was 0.5 mm², with larger areas on FAF. Growth rate of GA was 1.45 mm² from color photographs and 1.43 mm² from FAF images. The macula center was involved in 51 percent of color photographs and 56 percent of FAF images.

Researchers wrote that geographic atrophy may be detected earlier with use of FAF images, but noted that over the course of the study, the two modalities became comparable. They added that GA progression is comparable between color photographs and FAF images, but evaluating macula center involvement may differ, probably because of macular pigmentation blocking autofluorescence.

SOURCE: Domalpally A, Danis R, Agrón E, et al. Evaluation of geographic atrophy from color photographs and fundus autofluorescence images. Ophthalmology 2016; July 19. [Epub ahead of print].

Wide-field OCTA Using Extended Field Imaging to Evaluate Nonperfusion in RVO

Investigators wrote that a novel technique to expand the scan length on optical coherence tomography—imaging the posterior pole through trial frames fitted with a +20D lens—has been reported as an extended field imaging technique. Researchers applied this technique to OCTA to evaluate retinal vein occlusion.

The researchers studied 10 eyes of nine individuals with RVO with an average age of 69 years (range: 49-93 years). Researchers obtained OCTA images by using RTVue XR Avanti OCT with AngioVue at a scan size of 8×8 mm, with and without EFI, and compared them.

Investigators performed OCTA with EFI in all eyes. The nonperfusion area was well-defined in the superficial capillary plexus layer, and EFI images were able to capture the larger area of the fundus by an average of 188.5 percent than those without EFI. The posterior pole inside the vascular arcade was well-covered using the technique, and the fundus area was even larger than that of fluorescein angiography using Heidelberg Retina Angiograph 2, which captured a 30-degree field.

Investigators’ results suggested that OCTA with EFI is useful to evaluate the retinal ischemia in RVO.

Source: Kimura M, Nozaki M, Yoshida M, et al. Wide-field optical coherence tomography angiography using extended field imaging technique to evaluate the nonperfusion area in retinal vein occlusion. Clin Ophthalmol 2016:10:1291-5.

Chromatic Multifocal Pupillometer for Perimetry & Diagnosis of RP

In a study supported by Accutome (Malvern, Pa.), scientists assessed visual field defects and retinal function objectively in healthy participants and individuals with retinitis pigmentosa using a chromatic multifocal pupillometer, as part of a cross-sectional study. They examined the right eyes of 16 healthy participants and 13 people with RP. Israel’s Sheba Medical Center, where several of the investigators work, holds the patent for the device.

They recorded pupil responses to red and blue light (peak, 485 and 625 nm, respectively) presented by 76 light-emitting diodes, 1.8-mm spot size at different locations of a 16.2-degree VF. They determined subjective VFs of RP subjects using chromatic dark-adapted Goldmann VFs (CDA-GVFs). Six healthy participants underwent two pupillometer exams to determine test-retest reliability.

Scientists determined three parameters of pupil contraction automatically: percentage of pupil change (PPC); maximum contraction velocity (MCV; in pixels per second); and latency of MCV (LMCV; in seconds). CDA-GVF determined the fraction of functional VF.

In healthy participants, change of pupil size and MCV were measured in response to blue compared with red light. MCV latency in response to blue light was relatively constant throughout the VF. Healthy participants demonstrated higher PPC and MCV, and shorter central LMCV compared with peripheral test points in response to red light. Test-retest correlation coefficients were 0.7 for PPC and 0.5 for MCV. In RP subjects, test points in which the PPC and MCV were lower than four standard errors from the mean of healthy participants correlated with areas indicated as “non-seeing” by CDA-GVF. The mean absolute deviation in the LMCV parameter in response to the red light between different test points was significantly higher in RP subjects (range: 0.16 to 0.47) than in healthy participants (range: 0.02 to 0.16; p<0.0001), indicating its usefulness as a diagnostic tool with high sensitivity and specificity (AUC): 0.97, Mann-Whitney-Wilcoxon analysis). Randomly reducing the number of test points to 15 didn’t significantly reduce the RP diagnosis AUC based on this parameter.

Scientists wrote that the results demonstrated the feasibility of using a chromatic multifocal pupillometer for objective RP diagnosis and assessment of VF defects.

SOURCE: Chibel R, Sher I, Ben Ner D, et al. Chromatic multifocal pupillometer for objective perimetry and diagnosis of patients with retinitis pigmentosa. Ophthalmology 2016; July 15. [Epub ahead of print].

UWF Scanning Laser Ophthalmoscopy to Aid Detection & Evaluation of Asymptomatic, Early FEVR

Researchers assessed the ultra-wide-field scanning laser ophthalmoscope’s ability to clinically detect and evaluate asymptomatic, early-stage familial exudative vitreoretinopathy.

They retrospectively reviewed 163 eyes of 83 asymptomatic family members of 48 individuals with FEVR. UWF SLO imaging (Optos) was performed on asymptomatic family members as a preliminary screening test for fundus anomalies, and findings were compared with subsequent exams using indirect fundus ophthalmoscopy in full mydriasis, fluorescein angiography, fundus autoflourescence and genetic sequencing.

A total of 86 eyes of 43 asymptomatic family members were clinically diagnosed with early-stage FEVR, 17 of which were also genetically diagnosed. Compared with FA as a standard, UWF SLO was highly effective in diagnosing FEVR, with a 93-percent sensitivity and 97.5-percent specificity. UWF SLO was able to assist in diagnosing early-stage FEVR in 93 percent of eyes, and guided therapy selection in 46.5 percent of eyes.

Researchers suggested that UWF SLO is a valuable imaging tool for detecting fundus anomalies related to early-stage FEVR, and can assist in clinical diagnosis and evaluation of early-stage FEVR in asymptomatic family members of patients with FEVR.

SOURCE: Lyu J, Zhang Q, Wang S, et al. Ultra-wide-field scanning laser ophthalmoscopy assists in the clinical detection and evaluation of asymptomatic early-stage familial exudative vitreoretinopathy. Graefes Arch Clin Exp Ophthalmol 2016; July 14. [Epub ahead of print].