Racial differences in quantitative optical coherence tomography angiography findings between older non-diabetics with co-morbidities.

This cross-sectional study compared optical coherence tomography angiography (OCTA) parameters between older Black and White adults with systemic comorbidities in an effort to further understand racial differences in the retinal microvasculature. We analyzed vessel density at the superficial (SCP), intermediate (ICP), and deep capillary plexuses (DCP), foveal avascular zone (FAZ) parameters, and blood flow area (BFA) at the choriocapillaris. We used a mixed-effects linear regression model, controlling for hypertension and two eyes from the same subject, to compare OCTA parameters. Black subjects had lower foveal vessel density at the SCP and ICP, while no differences were observed at the parafovea or 3x3 mm macular area of any capillary layer. Black subjects had greater FAZ area, perimeter, and FD-300, a measurement of vessel density in a 300 µm wide ring around the FAZ. Black subjects also had lower BFA at the choriocapillaris. Within a cohort of subjects without hypertension, these differences remained statistically significant, with the exception of foveal vessel density at the SCP and foveal BFA of the choriocapillaris. These findings suggest that normative databases of OCTA parameters must strive to be diverse in nature to adequately capture differences across patient populations. Further study is required to understand if baseline differences in OCTA parameters contribute to epidemiological disparities in ocular diseases.

Computerized Texture Analysis of Optical Coherence Tomography Angiography of Choriocapillaris in Normal Eyes of Young and Healthy Subjects.

Computerized texture analysis uses higher-order mathematics to identify patterns beyond what the naked eye can recognize. We tested its feasibility in optical coherence tomography angiography imaging of choriocapillaris. Our objective was to determine sets of parameters that provide coherent and consistent output when applied to a homogeneous, healthy group of patients. This observational cross-sectional study involved 19 eyes of 10 young and healthy Caucasian subjects. En-face macular optical coherence tomography angiography of superficial choriocapillaris was obtained by the RTVue-XR Avanti system. Various algorithms were used to extract texture features. The mean and standard deviation were used to assess the distribution and dispersion of data points in each metric among eyes, which included: average gray level, gray level yielding 70% threshold and 30% threshold, balance, skewness, energy, entropy, contrast, edge mean gradient, root-mean-square variation, and first moment of power spectrum, which was compared between images, showing a highly concordant homology between all eyes of participants. We conclude that computerized texture analysis for en-face optical coherence tomography angiography images of choriocapillaris is feasible and provides values that are coherent and tightly distributed around the mean in a homogenous, healthy group of patients. Homology of blob size among subjects may represent a "repeat pattern" in signal density and thus a perfusion in the superficial choriocapillaris of healthy young individuals of the same ethnic background.

Evaluation of flow of chorioretinal capillaries in healthy black and white subjects using optical coherence tomography angiography.

This study compared macular capillary parameters between healthy black and white subjects using optical coherence tomography angiography (OCTA). We measured vessel density (VD) of superficial (SCP), intermediate (ICP), and deep (DCP) capillary plexuses and choriocapillaris blood flow area (BFA) of the fovea, parafovea and total 3 mm-diameter circular area centered on the fovea, as well as the foveal avascular zone (FAZ) parameters, controlling for axial length. Black subjects had lower foveal and parafoveal VD in the SCP (p = 0.043 and p = 0.014) and the ICP (p = 0.014 and p = 0.002). In the DCP, black subjects had a trend toward lower foveal and parafoveal VD. Black subjects had decreased choriocapillaris BFA in the total 3 mm area (p = 0.011) and the parafovea (p = 0.033), larger FAZ area (p = 0.006) and perimeter (p = 0.014), and a higher capillary density in a 300 µm wide region around the FAZ (FD-300) (p = 0.001). There was no significant difference in FAZ acircularity index. To our knowledge, this is the first report analyzing the three distinct retinal capillary plexuses and identifying differing baseline VD, choriocapillaris and FAZ parameters in healthy young black compared to white subjects. Larger studies are needed to validate these findings and better understand racial differences in vulnerability to ocular diseases.

Quantitative Optical Coherence Tomography Angiography (OCTA) Parameters in a Black Diabetic Population and Correlations with Systemic Diseases.

This is a cross-sectional, prospective study of a population of black diabetic participants without diabetic retinopathy aimed to investigate optical coherence tomography angiography (OCTA) characteristics and correlations with systemic diseases in this population. These parameters could serve as novel biomarkers for microvascular complications; especially in black populations which are more vulnerable to diabetic microvascular complications. Linear mixed models were used to obtain OCTA mean values ± standard deviation and analyze statistical correlations to systemic diseases. Variables showing significance on univariate mixed model analysis were further analyzed with multivariate mixed models. 92 eyes of 52 black adult subjects were included. After multivariate analysis; signal strength intensity (SSI) and heart disease had statistical correlations to superficial capillary plexus vessel density in our population. SSI and smoking status had statistical correlations to deep capillary plexus vessel density in a univariate analysis that persisted in part of the imaging subset in a multivariate analysis. Hyperlipidemia; hypertension; smoking status and pack-years; diabetes duration; creatinine; glomerular filtration rate; total cholesterol; hemoglobin A1C; and albumin-to-creatinine ratio were not significantly associated with any OCTA measurement in multivariate analysis. Our findings suggest that OCTA measures may serve as valuable biomarkers to track systemic vascular functioning in diabetes mellitus in black patients.

Recurrent Spontaneous Macular Hole Formation and Resolution in a Patient With Previous Vitrectomy.

Purpose: We report a case of recurrent macular hole (MH) formation and spontaneous closure in the absence of any vitreoretinal interface abnormality. Methods: A 49-year-old man presented for his annual ocular examination with no specific ocular complaints. He had a history of retinal detachment in the left eye, which was treated years prior with vitrectomy and scleral buckle. During a routine follow-up, the patient was discovered to have a full-thickness MH. Optical coherence tomography revealed the formation of an MH with spontaneous closure after 3 months without intervention. One month later, the MH recurred but once again closed spontaneously over 4 months. Results: The patient remained asymptomatic during the entire follow-up without any symptoms, vision changes, or therapeutic intervention. Conclusions: To our knowledge, this is the first known case report of recurrent spontaneous opening and closure of an MH in the absence of any vitreoretinal interface abnormality, as revealed by macular optical coherence tomography imaging.

Use of Fundus Autofluorescence Combined with Optical Coherence Tomography for Diagnose of Geographic Atrophy in Age-Related Macular Degeneration.

The aim of this study was to demonstrate the sensitivity of Optical coherence tomography (OCT) in detection of geographic atrophy (GA) secondary to exudative age related macular degeneration (AMD). In this retrospective case series study 77 patients (53% female, with mean ± standard deviation [SD] of 82.6±9.3 years) with 97 eyes (45 OS [left eyes]/52 OD [right eyes]) were included. This was a retrospective review of the charts of patients who presented with exudative AMD at the Pitié Salpetrière Hospital, Paris, France, between December 2016 and August 2017 that received intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) therapies. At baseline, following biomicroscopy examination, multimodal imaging was performed including, fluorescein angiography (FA), fundus auto-fluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) and indocyanine green angiography (ICGA). During the follow-up, SD-OCT with/without FAF and FA were performed for each patient at 6, 12 and 18 months. For investigation of the prevalence of GA in eyes undergoing intravitreal injections with anti-VEGF therapy, FAF and SD-OCT images were qualitatively reviewed by four independent observers (two graders per group). Kappa coefficient of Cohen was calculated to determine agreement between the graders. The kappa coefficient of Cohen, for inter-rater agreement in the evaluation of FAF images was 0.468, indicating a moderate agreement between the first and second raters. Thus, the sensitivity and specificity of FAF for the diagnosis of GA were 70% and 57%, respectively. If atrophy was assessed with SD-OCT image analysis, the kappa coefficient for inter-rater agreement was 0.846, implying an acceptable agreement between both readers. The sensitivity and specificity of SD-OCT were 93% and 58% respectively. In conclusion, SD-OCT image analysis was more sensitive than FAF for identifying GA in patients treated for exudative AMD.

Evaluation of outer retinal tubulations in eyes switched from intravitreal ranibizumab to aflibercept for treatment of exudative age-related macular degeneration.

PURPOSE: To evaluate the changes of outer retinal tubulations (ORTs) as seen on spectral-domain optical coherence tomography (SD OCT) in eyes with neovascular age-related macular degeneration (AMD) where treatment was switched from intravitreal ranibizumab to intravitreal aflibercept. METHODS: This was a prospective study of eyes diagnosed with neovascular AMD and previously treated with >6 intravitreal ranibizumab injections and switched to aflibercept, conducted at a single centre (Department of Ophthalmology at Pitié Salpetriere Hospital, Paris VI University) from January to July 2015. Before and after treatment was switched from ranibizumab to aflibercept, SD-OCT was used to evaluate the presence of ORTs. Additional assessments in this patient group included best-corrected visual acuity (BCVA), fluorescein angiography (FA), indocyanine green angiography (ICGA). Changes in pigment epithelium detachments (PED), presence of intraretinal cysts, and presence of subretinal fluid (SRF) were also noted. RESULTS: Twenty-four eyes of 24 consecutive patients (15 female/nine male, mean age 70 years) diagnosed with neovascular AMD and previously treated with >6 intravitreal ranibizumab injections and switched to aflibercept were included in the analysis. After receiving aflibercept, patients were followed for a mean of 6.1 months. Prior to treatment switch, 97 % of eyes showed ORTs, while after treatment switch to aflibercept, at the end of the study period, 75 % had ORTs (p = 0.219). Changes in BCVA (LogMAR) were not statistically significant (1.16 ± 0.44 to 1.18 ± 1.06, p = 0.12), however, a significant reduction in central macular thickness (CMT) (from 406 µm ± 112 to 263 µm ± 68, p = 0.001), PED (from 70.8 % to 41.7 % , p = 0.016), presence of intraretinal cysts (from 83.3 % to 33.3 %, p = 0.002) and SRF (from 91.7 % to 25 %, p = 0.001 ) were noted. CONCLUSION: After switching from ranibizumab treatment to aflibercept, ORTs remained present in 75 % of eyes, and significant reductions in CMT, PED, and SRF, and presence of intraretinal cysts were observed.

Evolving Knowledge in Pharmacologic Treatments of Age-Related Macular Degeneration.

Modern retinal drug therapy is a result of the recent challenges and breakthroughs in chemistry, physics, genetics, cell biology and biotechnologies. Specific pharmaceutical and pharmacokinetic characteristics of a drug are of major importance and contribute to its ability to penetrate targeted ocular tissues in order to result in effective therapeutic concentrations. In addition, the drugs should maintain a prolonged time of activity and be safe with minimal local and systemic toxicity. The transporter vehicle or drug delivery system is crucial in order to enhance ocular tissue penetration and establish controlled drug release. Administration methods should be local, thereby reducing systemic side effects, and, ideally, treatment should be noninvasive. Within the group of so-called classic therapies, the use of pharmacologic treatments has become widespread for most severe retinal diseases. Thereby, ocular therapy of diseases like exudative age-related macular degeneration has improved markedly. Moreover, new metabolic pathways have been identified, new molecules have emerged, new synthesis technologies have been discovered, and new formulae conceived. These developments have opened new avenues for limiting disease progression.

Multimodal analysis of the progression of Best vitelliform macular dystrophy.

PURPOSE: To investigate the multimodal morphological features in the different stages of Best vitelliform macular dystrophy (VMD) in subjects harboring mutations in the BEST1 gene, and their changes during the progression of the disease. METHODS: In this retrospective observational study performed between January 2007 and December 2012, 21 patients (42 eyes) with Best VMD from eight families with the BEST1 mutation were included. Best-corrected visual acuity (BCVA), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SDOCT) were evaluated at study entry and at last visit. RESULTS: The mean age of patients was 26.3±17.4 years. Seven new missense mutations in BEST1 were identified. Mean follow-up was 41.1±18.5 months. Mean BCVA was 0.34±0.34 LogMAR at study entry and 0.32±0.33 LogMAR at last follow-up visit (p = 0.2). The overall lesion area on FAF increased from 6.62±4.9 mm² to 7.34±6.1 mm² (p = 0.05). At study entry, on SD-OCT, photoreceptor inner segment ellipsoid portion (ellipsoid zone, EZ) was normal in 15 eyes, disrupted in 14 eyes, and absent in 13 eyes. In two eyes, EZ changed from normal to disrupted during follow-up. Three eyes of three patients showing pseudohypopyon lesions at study entry progressed to vitelliruptive lesions at the last follow-up visit. Three eyes of three patients showing vitelliruptive lesion at study entry reverted to pseudohypopyon lesion with overall enlargement of the lesion size. CONCLUSIONS: Multimodal analysis allowed documenting a continuous material accumulation and reabsorption in Best VMD progression. Blue FAF and SD-OCT could represent noninvasive imaging techniques to monitor Best VMD.

Impact of reticular pseudodrusen on macular function.

PURPOSE: To investigate the impact of reticular pseudodrusen on macular function using microperimetry. METHODS: Eighteen consecutive patients (18 eyes) with reticular pseudodrusen (Group 1), and without medium/large drusen, underwent microperimetry. Eighteen age-matched and sex-matched subjects (18 eyes) with typical drusen and without pseudodrusen (Group 2) also underwent microperimetry. Macular sensitivity was assessed by microperimetry and compared between the two Groups. RESULTS: Mean age of patients with reticular pseudodrusen and with typical drusen was 77.3 ± 6.8 years and 75.0 ± 9.9 years, respectively (P = 0.4), and 61.1% and 61.1% were women, respectively. Mean best-corrected visual acuity was 0.14 ± 0.09 logarithm of the minimum angle of resolution and 0.13 ± 0.09 logarithm of the minimum angle of resolution (P = 0.8) in Group 1 and Group 2, respectively. Microperimetry revealed a significant difference in overall mean macular sensitivity ("square 7 × 7"; 49 points) between Group 1 and Group 2 (5.9 ± 1.7 dB vs. 8.8 ± 2.4 dB, P < 0.001). Both mean central macular sensitivity ("square 3 × 3"; 9 points) and mean peripheral macular microperimetric sensitivity (overall "square 7 × 7" - central "square 3 × 3"; 40 points) were significantly reduced in Group 1 compared with Group 2 (central macular sensitivity: 6.9 ± 1.7 dB vs. 8.9 ± 2.6 dB in Group 1 and Group 2, respectively; P = 0.01; peripheral macular sensitivity: 5.7 ± 1.8 dB vs. 8.7 ± 2.3 dB in Group 1 and Group 2, respectively; P < 0.001). In Group 1, mean peripheral sensitivity was reduced when compared with mean central sensitivity (5.7 ± 1.8 dB vs. 6.9 ± 1.7 dB, P = 0.01), whereas in Group 2, mean sensitivity was similar in both peripheral and central macula (8.7 ± 2.3 dB vs. 8.9 ± 2.6 dB, P = 0.4). CONCLUSION: Eyes with reticular pseudodrusen present a greater extent of reduced sensitivity than eyes with typical drusen.

Evaluation of semiautomated measurement of geographic atrophy in age-related macular degeneration by fundus autofluorescence in clinical setting.

PURPOSE: To assess intraobserver and interobserver agreement among physicians with different degrees of clinical experience, using a novel fundus autofluorescence semiautomated software for quantification of geographic atrophy in clinical setting. METHODS: Fundus autofluorescence frames (excitation: 488 nm; emission: 500-700 nm) of 29 eyes (20 patients; mean age, 79.6 ± 6.2 years) with geographic atrophy secondary to age-related macular degeneration, and no signs of choroidal neovascularization, were analyzed using Region Finder, a semiautomated software embedded in Spectralis (Heidelberg Engineering, Heidelberg, Germany). For each study eye, semiautomated atrophy identification and quantification were independently performed, twice (in a 2-week time frame), by 3 readers with different degrees of clinical experience (2 fellows, and 1 resident). Intraobserver and interobserver agreements were assessed. RESULTS: Mean difference in intraobserver agreement (Bland-Altman statistics) ranged from -0.17 mm² to 0.13 mm². Intraobserver agreement was excellent until the geographic atrophy threshold value of 15.72 mm². Variability correlated with the size of atrophy. Mean difference in interobserver agreement (Bland-Altman statistics) ranged from -0.25 mm² to 0.27 mm², with no significant difference between senior and junior readers. Multifocal lesion or foveal involvement in atrophy was not the cause of disagreement. CONCLUSION: Region Finder is a reliable tool for the identification and quantification of geographic atrophy in patients with age-related macular degeneration, in a clinical setting even when performed by junior reader.

Functional characterization and multimodal imaging of treatment-naive "quiescent" choroidal neovascularization.

PURPOSE: To investigate the multimodal morphological and functional characteristics of treatment-naïve "quiescent" choroidal neovascularization (CNV) secondary to AMD. METHODS: Eleven patients with treatment-naïve "quiescent" CNV that consecutively presented over a 6-month period, underwent multimodal morphological and functional assessment (including indocyanine green angiography [ICGA], spectral-domain optical coherence tomography [SD-OCT], microperimetry, and preferential hyperacuity perimeter [PHP]). For the purpose of this study, asymptomatic previously untreated CNVs showing absence of intraretinal/subretinal exudation in two consecutive visits (at least 6 months apart) were defined as treatment-naïve "quiescent" CNV. RESULTS: Eleven eyes of 11 patients (9 females; mean age 76.5 ± 8.5 years) were included. On fluorescein angiography (FA), "quiescent" CNVs appeared as late speckled hyperfluorescent lesions lacking well-demarcated borders. Mid-late phase ICGA allowed visualizing the hyperfluorescent "quiescent" CNV network and delineating the plaque. Mean lesion area (mid-late phase ICGA) appeared larger compared with earliest previous examination performed 23.8 ± 16.0 months before (3.24 ± 2.51 mm(2) vs. 3.52 ± 2.46 mm(2), respectively; P = 0.01). SD-OCT revealed, at the site of "quiescent" CNV, an irregularly slightly elevated RPE, without hyporeflective intraretinal/subretinal fluid, showing a major axis in the horizontal plane, which was characterized by collections of moderately reflective material in the sub-RPE space and clear visualization of the hyperreflective Bruch's membrane. Hypergeometric distribution revealed a significant correlation between microperimetry and PHP with respect to locations of "affected areas" (P = 0.001). CONCLUSIONS: "Quiescent" CNVs are sub-RPE CNVs secondary to AMD, showing absence of intraretinal/subretinal exudation on repeated OCT. "Quiescent" CNVs enlarge over time and may contribute to local reduced retinal sensitivity and metamorphopsia.

Reticular pattern dystrophy of the retina: a spectral-domain optical coherence tomography analysis.

PURPOSE: To analyze the outer retinal and retinal pigment epithelium (RPE) features of reticular pattern dystrophy of the retina using spectral-domain optical coherence tomography (SDOCT). DESIGN: Retrospective observational case series. METHODS: Consecutive patients with reticular pattern dystrophy of the retina underwent a complete ophthalmologic examination, including assessment of best-corrected visual acuity (BCVA), fundus biomicroscopy, fluorescein angiography (FA), and SDOCT. RESULTS: Twenty-two eyes of 13 patients (6 men, 7 women, mean age 68.6 ± 14.5 years) were included. In the foveal area, the RPE layer appeared normal in 45.5% of eyes, while small RPE elevations and RPE bumps were detected in 31.8% and 22.7% of eyes, respectively. The SDOCT scans showed disruption of inner segment/outer segment (IS/OS) junction in 54.6% of eyes, a slight elevation in 59.1% of eyes, and an absence in 45.5% of eyes. The outer limiting membrane (OLM) appeared disrupted in 50.0% of eyes, absent in 22.7% of eyes, and elevated in 63.6% of eyes. Hyper-reflective subretinal material accumulation or hyporeflective subretinal lesions in the retrofoveolar region were detected in 70% and in 20% of eyes, respectively. SDOCT showed hyporeflective retinal pseudocysts in 13.6% of eyes. CONCLUSION: In this study on reticular pattern dystrophy of the retina, SDOCT provided a description of the material deposits and the alterations of the RPE and the different retinal layers. We observe that the lesions present specific features distinct from other macular dystrophies, but closer to those reported in fundus flavimaculatus than those reported in adult-onset foveomacular vitelliform dystrophy. Further analyses are needed, particularly to analyze the progression of the lesions.

Precursors of type 3 neovascularization: a multimodal imaging analysis.

PURPOSE: To study the advent of exudative age-related macular degeneration in uninvolved fellow eyes of patients with unilateral Type 3 neovascularization and to investigate the precursors at the site of lesion development. METHODS: We studied 37 consecutive patients with the diagnosis of unilateral Type 3 neovascularization, for the advent of exudative age-related macular degeneration in uninvolved fellow eyes (study eyes). Looking for the precursors of Type 3 neovascularization, we reviewed the multimodal imaging (fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and spectral-domain optical coherence tomography) in the study eyes and interpreted the changes over time at the site of lesion development. RESULTS: Of the 37 patients, 12 (32%) developed exudative age-related macular degeneration in the study eye, after a mean of 19.6 ± 9.5 months (range, 9-36 months) from the diagnosis of Type 3 neovascularization in the first involved eye (baseline). All these patients (12 of 12 eyes; 100%) developed Type 3 neovascularization in the study eye. Retrospective analysis of the precursors of these lesions revealed, at baseline, a focal hyperautofluorescence (fundus autofluorescence) that turned to focal hypoautofluorescence over time. In all eyes, a focal hyperfluorescence (fluorescein angiography and indocyanine green angiography) appeared over time at the site of Type 3 neovascularization development. The corresponding spectral-domain optical coherence tomography showed a localized retinal pigment epithelial (RPE) elevation characterized by a focal disruption of the RPE and photoreceptors and by the overlying outer plexiform layer that progressively took contact with the RPE. Based on these findings, it seems that a small, localized RPE elevation might be the lesion before the development of Type 3 neovascularization. This precursor lesion progresses over time to focal atrophy of RPE and photoreceptor. CONCLUSION: Type 3 neovascularization presents a predictable symmetry and bilaterality. Identification of the precursors of Type 3 neovascularization looks particularly useful for clinicians to detect the earliest changes in the vasogenic process in the fellow eye.

Spectral-domain optical coherence tomography of early onset large colloid drusen.

PURPOSE: Large colloid drusen (LCD) are a subgroup of early onset drusen recently reported. The aim of this study was to describe morphologic features in patients affected with LCD using high-resolution spectral-domain optical coherence tomography (SD-OCT). METHODS: A complete ophthalmologic examination including SD-OCT was performed in 22 eyes of 11 consecutive patients. RESULTS: Mean age was 35 years old at diagnosis, and mean visual acuity was 20/25. In all eyes, SD-OCT showed multiple dome-shaped retinal pigment epithelium detachments corresponding to the drusen. Mean height of drusen was 199 µm (range, 108-316 µm) and mean width was 419 µm (range, 190-681 µm). Indocyanine green angiography hypofluorescent LCD were larger and more reflective on SD-OCT than indocyanine green angiography hyperfluorescent LCD. All drusen appeared convex with medium and homogeneous internal reflectivity. Retina overlying LCD appeared wavy and overall thinned. Prominent diffuse hyperreflective haze in the Henle fiber layer over drusen was noted in 73% of the eyes. No geographic atrophy or choroidal neovascularization was observed. CONCLUSION: The peculiar SD-OCT features reported in the current series give insight on the ultrastructure of LCD. Further studies with follow-up evaluation and possibly histologic evaluation are needed to clarify the clinical significance of LCD.