In vivo optical imaging of human retinal capillary networks using speckle variance optical coherence tomography with quantitative clinico-histological correlation.

Retinal capillary networks are critically linked to neuronal health and disease. The ability to perform accurate in vivo examination of human retinal capillary networks is therefore valuable for studying mechanisms that govern retinal homeostasis and retinal vascular diseases. Speckle variance optical coherence tomography (svOCT) is a non-invasive imaging technique that has the capacity to provide angiographic information about the retinal circulation. The application of this technology for studying human retinal capillary networks however has not been validated in a quantifiable manner. We use a custom-built svOCT device to qualitatively and quantitatively study the various capillary networks in the human perifovea. Capillary networks corresponding to the nerve fibre layer (NFL), the retinal ganglion cell/superficial inner plexiform layer (RGC/sIPL), the deep inner plexiform layer/superficial inner nuclear layer (dIPL/sINL) and the deep inner nuclear layer (dINL) are imaged in 9 normal human subjects. Measurements of capillary diameter and capillary density are made from each of these networks and results are compared to post-mortem histological data acquired with confocal scanning laser microscopy. Additionally, retinal capillary measurements from high-resolution fundus fluorescein angiogram (FA) are directly compared with svOCT images from 6 eyes. We demonstrate that svOCT images of capillary networks are morphologically comparable to microscopic images of histological specimens. Similar to histological images in svOCT images, the capillaries in the NFL network run parallel to the direction of RGC axons while capillaries in the dINL network comprise a planar configuration with multiple closed loops. Capillaries in remaining networks are convoluted with a complex three-dimensional architecture. We demonstrate that there is no significant difference in capillary density measurements between svOCT and histology images for all networks. Capillary diameter was significantly greater in svOCT images compared to histology for all networks. Capillary density measurements were also higher in svOCT compared to FA. The results of this study suggest that in vivo svOCT imaging allows accurate morphometric assessment of capillary networks in the human perifovea and may provide an improved ability to render microvascular detail compared to FA. Therefore, svOCT may have broad clinical applications in the study of human retinal physiology and disease. The difference in quantitative measurements between svOCT and histology may reflect dynamic variations in the retinal microcirculation and warrants further investigation.

Exacerbation of choroidal and retinal pigment epithelial atrophy after anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration.

PURPOSE: To study the progression of retinal pigment epithelium (RPE) and choroidal atrophy in patients with neovascular age-related macular degeneration (AMD) and to assess for a possible association with the number and type of anti-vascular endothelial growth factor treatments. METHODS: Patients with neovascular AMD and a minimum of 1-year follow-up were reviewed. Fellow eyes with nonneovascular AMD were used as control eyes. Retinal pigment epithelial atrophy area and choroidal thickness were determined using spectral-domain optical coherence tomography. Multivariable regression models were used for statistical analyses. RESULTS: A total of 415 eyes were included in the study, with a mean follow-up of 2.2 years. Eyes with neovascular AMD had greater progression of RPE atrophy and choroidal atrophy compared with those with nonneovascular AMD (P < 0.001). Progression of RPE atrophy and choroidal atrophy was independently associated with the total number of injections of bevacizumab and ranibizumab (all P values ≤ 0.001). In the subgroup of 84 eyes with neovascular AMD and without RPE atrophy at baseline, only bevacizumab was associated with the progression of RPE atrophy (P = 0.003). This study likely lacked statistical power to detect an association with ranibizumab in this subgroup. CONCLUSION: Retinal pigment epithelial atrophy and choroidal atrophy in neovascular AMD seem to be exacerbated by anti-vascular endothelial growth factor treatment. Possible differences between bevacizumab and ranibizumab require further investigation.

Rates of endophthalmitis before and after transition from povidone-iodine to aqueous chlorhexidine asepsis for intravitreal injection.

OBJECTIVE: To assess the rate of post-intravitreal injection endophthalmitis between 2 asepsis groups: aqueous chlorhexidine 0.1% and povidone-iodine 5%. DESIGN: Retrospective, observational cohort study. PARTICIPANTS: Patients with infectious endophthalmitis post intravitreal injection (n = 58) at a single centre from July 2009 to July 2022. METHODS: Retrospective chart review of all patients receiving intravitreal injections (216 593 injections) at a single centre over 14 years. Patients from July 2009 to February 2017 received povidone-iodine 5%, and patients from March 2017 to July 2022 received aqueous chlorhexidine 0.1%. Assessed characteristics of endophthalmitis cases included demographics, visual function, intervention type, and microbiological results. RESULTS: The rate of endophthalmitis was comparable for povidone-iodine (1.4:5000) and aqueous chlorhexidine (1.3:5000) (p = 0.77). Vitreous cultures were negative for 55% of patients. Visual acuity (VA) outcomes did not differ between asepsis groups nor between culture positive/negative groups. Patients having vitrectomy (PPV) had worse final vision (p = 0.08) but there was no VA difference between early and late PPV. CONCLUSIONS: Aqueous chlorhexidine 0.1% is a viable and safe alternative to povidone-iodine 5% for post-intravitreal injection endophthalmitis prophylaxis and may reduce ocular surface adverse events and discomfort.

Physical, Psychosocial, and Practical Burden of Patients Receiving Care for Age-Related Macular Degeneration in Canada: A Mixed-Methods Qualitative Study.

Purpose: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss. Documentation of the disease's description and treatment experience of Canadian patients is limited but of interest given the aging population and resultant implications for healthcare systems. A mixed-methods study was conducted to understand the challenges experienced by patients living in Canada with AMD to identify areas of need and for potential reform. Patients and Methods: Canadian residents with wet or dry AMD were eligible for participation in an online survey and one-on-one telephone interview regarding their disease experience. Participants were recruited via a not-for-profit stakeholder organization and an ophthalmology clinic. Surveys were completed from January-June 2020 and interviews were conducted from November-December 2020, with findings reported using descriptive statistics and thematic analysis, respectively. Results: Findings from 303 survey responses and 20 interviews were analyzed. Most participants indicated their vision loss negatively impacts their ability to conduct daily activities (eg, self care, driving) and leads to constant worry, loneliness, and/or isolation. Participants frequently reported requiring caregiver support, often for eye appointment travel or everyday tasks. Regardless of AMD type, participants reported having several appointments each year, and that time spent travelling to/from and waiting at appointments and related costs were considerable. Although participants receiving anti-vascular endothelial growth factor injections valued treatment, the experience added additional burden related to anxiety, fear, pain, and even greater reliance on caregivers. Many participants indicated they felt poorly informed about their disease and treatment options, particularly at diagnosis, which increased their emotional burden. Conclusion: Patients with AMD living in Canada experience a significant and persistent mental, physical, and financial burden as a direct result of their disease. Improvements to provision of disease-related information, support of daily activities and appointment attendance, and the overall treatment experience could substantially enhance outcomes among the growing population of patients with AMD.

Outcomes of Scleral Buckling After Failed Pneumatic Retinopexy.

Purpose: To assess the visual and anatomic outcomes of eyes that had secondary scleral buckle (SB) surgery after unsuccessful pneumatic retinopexy (PR) for rhegmatogenous retinal detachment (RRD). Methods: A retrospective study, performed over a 12-year period, comprised patients who had secondary SB procedures after failed primary PR. Clinical parameters (eg, best-corrected visual acuity [BCVA], lens status, macula status, details of RRD and subretinal fluid) were assessed at presentation, before additional procedures, and at follow-up (6 months, 1 year, and last visit). Statistical comparisons were made using Brown-Forsythe and Welch analysis-of-variance tests, with significance levels set at P < .05. Results: Fifty-four eyes with adequate follow-up were included. Forty-four (81.5%) of 54 eyes had successful retinal reattachment with secondary SB alone. The remaining eyes had subsequent pars plana vitrectomy (PPV). Patients presenting with macula-on RRD who had successful secondary SB had no statistically significant change in BCVA from baseline (mean final, 0.23 ± 0.25 logMAR [Snellen 20/34]; P = .999). There was a statistically significant improvement in BCVA in patients presenting with macula-off RRD who had successful secondary SB (mean final, 0.32 ± 0.36 logMAR [20/42]; P < .001 and mean change, -1.06 ± 0.85 logMAR). Ten patients presenting with macula-off RRD who had failed secondary SB had a significant improvement in the final BCVA (mean final, 0.22 ± 0.28 logMAR [20/33]; P = .044), despite the need for an additional PPV to achieve reattachment. Conclusions: Secondary SB remains a good option for RRD repair after unsuccessful PR and may avoid the need for PPV.

Optical coherence tomography-based correlation between choroidal thickness and drusen load in dry age-related macular degeneration.

PURPOSE: Spectral domain optical coherence tomography can be used to measure both choroidal thickness and drusen load. The authors conducted an exploratory study using spectral domain optical coherence tomography to determine if a correlation between choroidal thickness and drusen load exists in patients with dry age-related macular degeneration. METHODS: Forty-four patients with dry age-related macular degeneration were recruited. The drusen area and volume were determined using the automated software algorithm of the spectral domain optical coherence tomography device, and choroidal thickness was measured using enhanced depth imaging. Correlations were determined using multivariable and univariable analyses. RESULTS: The authors found an inverse correlation between choroidal thickness and drusen load (r = -0.35, P = 0.04). Drusen load was also correlated with visual acuity (r = 0.32, P = 0.04). A correlation between choroidal thickness and visual acuity was suggested (r = -0.22, P = 0.21). CONCLUSION: Spectral domain optical coherence tomography can be used to assess the correlation between drusen load and choroidal thickness, both of which show a relationship with visual acuity. The measurement of these outcomes may serve as important outcome parameters in routine clinical care and in clinical trials for patients with dry age-related macular degeneration.

Incidence of ocular hypertension after anti-VEGF injections: examining the effect of drug filtration and silicone-free syringes.

OBJECTIVE: To examine the difference in incidence of ocular hypertension (OHT) following the introduction of filtered anti-vascular endothelial growth factor (anti-VEGF) medication in silicone-free syringes. DESIGN: Retrospective cohort study. METHODS: A retrospective review of consecutive treatment-naive patients receiving intravitreal anti-VEGF injections in a group practice was performed. Data from the cohort receiving nonfiltered anti-VEGF in insulin syringes (IS group) was collected from June 2015. Data from the cohort receiving filtered anti-VEGF in silicone-free syringes (SFS group) was collected from June 2019. Follow up data were collected at 1 year. Exclusion criteria included prior anti-VEGF treatment, known glaucoma or diagnosis of glaucoma suspect before anti-VEGF treatment, neovascular glaucoma, steroid use, or vitrectomy during follow-up. Primary outcome was the cumulative incidence of intraocular pressure (IOP) > 21 mmHg and IOP ≥ 30 mm Hg at any follow-up visit. The use of IOP lowering therapy was also recorded. RESULTS: The mean age (71 ± 13 years), mean number of injections (9.6 ± 2.7), and median follow-up time (392 ± 57 days) were similar between groups. The incidence of IOP ≥ 21 mm Hg was 34% (34/100) in the IS group and 15% (15/100) in the SFS group (p = 0.025). The incidence of IOP ≥ 30 mm Hg was 8% (8/100) in the IS group and 0% (0/100) in the SFS group (p =0.004). The incidence of IOP-lowering therapy was 13% in the IS group and 0% in the SFS group (p =0.0002). CONCLUSION: The incidence of OHT and treatment with IOP-lowering therapy significantly decreased after the introduction of filtered anti-VEGF medication and silicone-free syringes.

CRYSTALLINE RETINOPATHY AND RETINAL VASCULOPATHY IN CALCIFIC UREMIC ARTERIOLOPATHY (CALCIPHYLAXIS).

PURPOSE: To report the posterior segment and retinal vascular manifestations of calcific uremic arteriolopathy (calciphylaxis). Clinical findings are correlated with multimodal imaging results. METHODS: Observational case report. RESULTS: A 65-year-old white woman on hemodialysis was referred for assessment of poor vision bilaterally. Clinical examination demonstrated a crystalline retinopathy with stigma of previous retinal arterial occlusion. Fluorescein angiography revealed delayed retinal arterial filling bilaterally, sheathing of vessels, and peripheral nonperfusion. The crystals were hyperautofluorescent. Spectral domain and enhanced depth imaging optical coherence tomography localized the crystals within the retina with a predilection for the retinal arterial vasculature. The choriocapillaris was not involved. Two years prior, the patient developed necrotic skin lesions which were biopsied and confirmed the diagnosis of calciphylaxis. CONCLUSION: Calcific uremic arteriolopathy is an extremely rare cause of thrombogenic microangiopathy in end-stage renal disease patients. Retinal arterial occlusion appears to be a rare but significant cause of visual loss in this disease and is likely to be consequent to crystalline deposition in the retinal vasculature.

Comparison of endophthalmitis rates following intravitreal injection of compounded bevacizumab, ranibizumab, and aflibercept.

OBJECTIVE: Whereas the incidence of endophthalmitis after compounded intravitreal bevacizumab is known to be low, the rates of endophthalmitis after intravitreal injection of compounded ranibizumab and aflibercept are not known. The purpose of this study was to determine the incidence of endophthalmitis after treatment with compounded intravitreal ranibizumab and aflibercept and to compare this to the incidence with compounded intravitreal bevacizumab. DESIGN: Retrospective chart review. PARTICIPANTS: All patients with post-injection endophthalmitis who were seen over a 6.5-year period at a tertiary retina referral practice. METHODS: We identified all cases of endophthalmitis by searching for patients who received intravitreal antibiotics and had antecedent intravitreal injection of bevacizumab, ranibizumab, or aflibercept. RESULTS: A total of 54,101 injections of bevacizumab, 5,614 injections of ranibizumab, and 3,468 injections of aflibercept were performed. The incidence of suspected endophthalmitis was 0.041% (95% CI: 0.026-0.062) for bevacizumab, 0.036% (95% CI: 0.0043-0.13) for ranibizumab, and 0.06% (95% CI: 0.007-0.2) for aflibercept. For culture-positive cases, the incidence was 0.017% (95% CI: 0.0076-0.032) for bevacizumab, 0.02% (95% CI: 0.0005-0.1) for ranibizumab, and 0.03% (95% CI: 0.0007-0.2) for aflibercept. There was no statistically significant difference in endophthalmitis rate between the 3 different compounded drugs with respect to both overall suspected endophthalmitis rate and culture-positive endophthalmitis rate (p = 0.87). CONCLUSION: Compounding of ranibizumab and aflibercept for intravitreal use appears to be safe because the endophthalmitis rate does not appear to be different from that of intravitreal bevacizumab.

Strip-based registration of serially acquired optical coherence tomography angiography.

The visibility of retinal microvasculature in optical coherence tomography angiography (OCT-A) images is negatively affected by the small dimension of the capillaries, pulsatile blood flow, and motion artifacts. Serial acquisition and time-averaging of multiple OCT-A images can enhance the definition of the capillaries and result in repeatable and consistent visualization. We demonstrate an automated method for registration and averaging of serially acquired OCT-A images. Ten OCT-A volumes from six normal control subjects were acquired using our prototype 1060-nm swept source OCT system. The volumes were divided into microsaccade-free en face angiogram strips, which were affine registered using scale-invariant feature transform keypoints, followed by nonrigid registration by pixel-wise local neighborhood matching. The resulting averaged images were presented of all the retinal layers combined, as well as in the superficial and deep plexus layers separately. The contrast-to-noise ratio and signal-to-noise ratio of the angiograms with all retinal layers (reported as average ± standard deviation ) increased from 0.52 ± 0.22 and 19.58 ± 4.04 ?? dB for a single image to 0.77 ± 0.25 and 25.05 ± 4.73 ?? dB , respectively, for the serially acquired images after registration and averaging. The improved visualization of the capillaries can enable robust quantification and study of minute changes in retinal microvasculature.

Characterization of lymphoproliferative lesions of the conjunctiva: immunohistochemical and molecular genetic studies.

BACKGROUND: Conjunctival lymphoproliferative lesions have not been selected for independent analysis with newer immunohistochemical and molecular genetic techniques to highlight their unique profile. METHODS: Retrospective case series examined biopsies from 16 consecutive patients with conjunctival lymphoproliferative lesions. The histopathologic, immunohistochemical, and molecular genetic features were characterized, as well as the frequency of tumour type, prognostic implications, clinical features, and treatments offered. RESULTS: The diagnosis was lymphoma in 12 cases, atypical lymphoid hyperplasia (ALH) in 1 case, and reactive lymphoid hyperplasia (RLH) in 3 cases. The primary lymphomas consisted of 4 mucosa-associated lymphoid tissue lymphomas (MALTL), 1 follicular lymphoma (FL), 2 diffuse large B-cell lymphomas (DLBCLs), 1 lymphoplasmacytic lymphoma, and 1 T-cell lymphoma. Primary lymphomas were treated with radiation (n = 7), surgery (n = 1), and topical chemotherapy (n = 1). Complete remission was achieved in 8 of 9 primary lymphomas. Two cases of recurrence to the other conjunctiva were treated with radiation and both remained disease free. Secondary lymphomas included 2 DLBCL and 1 MALTL. Complete remission was seen in 2 patients after radiation plus chemotherapy, while the patient treated with chemotherapy alone was lost to follow-up. The 1 case of ALH presented bilaterally and achieved complete remission after topical chemotherapy treatments. The 3 RLH cases were surgically managed and 2 of the 3 recurred and were subsequently excised. Eleven lymphomas were of B-cell lineage by immunophenotyping. Molecular genetic studies of immunoglobulin heavy chain (IgH) gene rearrangement by polymerase chain reaction (PCR) showed clonal bands in 6 of 12 lymphomas, 1 of 3 RLH (polyclonal by immunophenotyping) and 1 ALH. BCL2-IgH [t(14;18)] rearrangement was seen in 8 of 12 cases (1 FL, 3 DLBCLs, 4 MALTLs) by real-time quantitative PCR. INTERPRETATION: Conjunctival lymphomas are predominantly B-cell type with a high prevalence of MALTL. An unexpected finding was the BCL2-IgH rearrangement seen in 4 of 5 MALTL cases in our series. The significance of this remains unclear.

Segmentation of the foveal microvasculature using deep learning networks.

Accurate segmentation of the retinal microvasculature is a critical step in the quantitative analysis of the retinal circulation, which can be an important marker in evaluating the severity of retinal diseases. As manual segmentation remains the gold standard for segmentation of optical coherence tomography angiography (OCT-A) images, we present a method for automating the segmentation of OCT-A images using deep neural networks (DNNs). Eighty OCT-A images of the foveal region in 12 eyes from 6 healthy volunteers were acquired using a prototype OCT-A system and subsequently manually segmented. The automated segmentation of the blood vessels in the OCT-A images was then performed by classifying each pixel into vessel or nonvessel class using deep convolutional neural networks. When the automated results were compared against the manual segmentation results, a maximum mean accuracy of 0.83 was obtained. When the automated results were compared with inter and intrarater accuracies, the automated results were shown to be comparable to the human raters suggesting that segmentation using DNNs is comparable to a second manual rater. As manually segmenting the retinal microvasculature is a tedious task, having a reliable automated output such as automated segmentation by DNNs, is an important step in creating an automated output.

Quantitative Optical Coherence Tomography Angiography of Radial Peripapillary Capillaries in Glaucoma, Glaucoma Suspect, and Normal Eyes.

PURPOSE: To evaluate the quantitative characteristics of the radial peripapillary capillary (RPC) network in glaucoma, glaucoma suspect, and normal eyes using speckle variance optical coherence tomography angiography (OCT-A). To determine correlations between RPC density, nerve fiber layer (NFL) thickness, and visual field indices. DESIGN: Cross-sectional study. METHODS: OCT-A images of RPCs were acquired at a single institution using a custom-built 1060 nm system from 3 groups: unilateral glaucoma (10 eyes from 5 subjects), glaucoma suspects (6 eyes from 3 subjects), and normal control eyes (16 eyes from 9 normal subjects). Peripapillary NFL thickness measurements were determined using spectral-domain optical coherence tomography. Glaucoma and glaucoma suspects also underwent automated 30-2 Humphrey visual field analysis. Manual tracing techniques were used to quantify RPC density in the OCT-A images. Data were analyzed using a linear mixed model with 1 fixed-effect covariate. Correlations between main outcome measures (RPC density, NFL thickness, and visual field index) were determined. RESULTS: Mean age was not significantly different between the 3 groups (P = .25). The density of RPCs was significantly lower in glaucomatous eyes compared with matched-peripapillary regions in the fellow eye, glaucoma suspect group, and normal group (all P < .001). RPC density was strongly correlated with NFL thickness (P < .001) and visual field index (P < .001). CONCLUSIONS: Significant reductions in RPC density were correlated with sites of NFL decrease and visual field loss in glaucoma. Speckle variance OCT-A allows visualization and quantification of RPCs and may therefore be a useful tool for indirectly quantifying and monitoring retinal ganglion cell axonal injury in glaucoma.

Alterations in intraocular cytokine levels following intravitreal ranibizumab.

OBJECTIVE: Our previous work has shown that, after intravitreal bevacizumab (IVB) administration, decreases in the levels of vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF), along with increases in the levels of interleukin (IL)-8 and transforming growth factor (TGF)-ß2, can be observed. It is not yet known if similar changes occur after intravitreal ranibizumab (IVR). The purpose of this study was to examine intraocular cytokine changes after IVR. DESIGN: Prospective clinical study. PARTICIPANTS: Subjects with proliferative diabetic retinopathy requiring pars plana vitrectomy (PPV) were recruited. METHODS: Participants received IVR as pre-treatment before PPV. Aqueous humour levels of IL-8, VEGF-A, PlGF, and TGF-ß2 were measured at time of pre-treatment and PPV. Results were analyzed using univariate statistical models. RESULTS: A total of 14 participants were recruited. After IVR administration, we observed a decrease in the levels of VEGF-A and PlGF, and an increase in the levels of IL-8 and TGF-ß2. These results were statistically significant only for VEGF-A (p = 0.0001) and IL-8 (p = 0.0002). CONCLUSIONS: The changes in cytokine levels after IVR mirror the changes seen after IVB. Further studies are warranted in order to determine if there are any differences between IVB and IVR in this regard.

Quantitative Comparison of Retinal Capillary Images Derived By Speckle Variance Optical Coherence Tomography With Histology.

PURPOSE: The purpose of this study was to correlate human retinal capillary network information derived from a prototype speckle variance optical coherence tomography (svOCT) device with histology to determine the utility of this instrument for quantitative angiography. METHODS: A retina location 3 mm superior to the optic disk was imaged with svOCT in 14 healthy human eyes. Qualitative and quantitative features of capillary networks, including capillary diameter and density, were compared with perfusion-labeled histological specimens from the same eccentricity. Twelve human donor eyes with no history of eye disease were used for histological comparisons. RESULTS: svOCT was able to clearly distinguish the morphological features of the nerve fiber layer capillary network, the retinal ganglion cell (RGC) layer capillary network, the capillary network at the border of the inner plexiform layer and superficial boundary of the inner nuclear layer, and the capillary network at the boundary of the deep inner nuclear layer and outer plexiform layer. The morphological features of these networks were highly comparable to those in previous histological studies. There were no statistical differences in mean capillary diameter between svOCT images and histology for all networks other than the RGC capillary network. Capillary density measurements were significantly greater in svOCT images, except in the RGC capillary network. CONCLUSIONS: svOCT has the capacity to provide histology-like anatomical information about human retinal capillary networks in vivo. It may have great potential as a research and diagnostic tool in the management of retinal vascular diseases. Further work is required to clarify the cause of some quantitative differences between svOCT and histology.

Quantitative Noninvasive Angiography of the Fovea Centralis Using Speckle Variance Optical Coherence Tomography.

PURPOSE: To demonstrate the utility of speckle variance optical coherence tomography (svOCT), a noninvasive angiographic technique, for evaluating the foveal vasculature. METHODS: Twelve normal human eyes were imaged with svOCT (1060-nm, 100-kHz custom-built system) and fluorescein angiography (FA; Topcon TRC-50DX with 5.0 megapixel resolution camera). Manual tracing techniques were used to quantify the foveal vasculature, including foveal avascular zone (FAZ) metrics (area, perimeter, greatest diameter, and lowest diameter). Reproducibility of these measurements was determined. The FAZ was imaged in 25 normal eyes using svOCT and 15 donor eyes using confocal scanning laser microscopy. Retinal capillary plexuses in donor eyes were perfusion-labeled with phalloidin conjugated to Alexa Fluor 546. RESULTS: Speckle variance OCT is able to stratify the foveal circulation into inner and deep capillary plexuses as well as reliably quantify and assess the morphometric dimensions of the human FAZ. Capillary density measurements were significantly greater in svOCT than FA (31.2 ± 1.6% vs. 19.3 ± 1.9% of total tissue area; P < 0.001). Measurements were highly reproducible (all P > 0.366). All FAZ metrics were significantly lower in histology than svOCT (all P < 0.001). CONCLUSIONS: Speckle variance OCT permits precise, reproducible, and noninvasive visualization of the human foveal vasculature. Speckle variance OCT may become an important adjunct in evaluating patients with retinal vascular diseases.

Label-Free Density Measurements of Radial Peripapillary Capillaries in the Human Retina.

Radial peripapillary capillaries (RPCs) comprise a unique network of capillary beds within the retinal nerve fibre layer (RNFL) and play a critical role in satisfying the nutritional requirements of retinal ganglion cell (RGC) axons. Understanding the topographical and morphological characteristics of these networks through in vivo techniques may improve our understanding about the role of RPCs in RGC axonal health and disease. This study utilizes a novel, non-invasive and label-free optical imaging technique, speckle variance optical coherence tomography (svOCT), for quantitatively studying RPC networks in the human retina. Six different retinal eccentricities from 16 healthy eyes were imaged using svOCT. The same eccentricities were histologically imaged in 9 healthy donor eyes with a confocal scanning laser microscope. Donor eyes were subject to perfusion-based labeling techniques prior to retinal dissection, flat mounting and visualization with the microscope. Capillary density and diameter measurements from each eccentricity in svOCT and histological images were compared. Data from svOCT images were also analysed to determine if there was a correlation between RNFL thickness and RPC density. The results are as follows: (1) The morphological characteristics of RPC networks on svOCT images are comparable to histological images; (2) With the exception of the nasal peripapillary region, there were no significant differences in RPC density measurements between svOCT and histological images; (3) Capillary diameter measurements were significantly greater in svOCT images compared to histology; (4) There is a positive correlation between RPC density and RNFL thickness. The findings in this study suggest that svOCT is a reliable modality for analyzing RPC networks in the human retina. It may therefore be a valuable tool for aiding our understanding about vasculogenic mechanisms that are involved in RGC axonopathies. Further work is required to explore the reason for some of the quantitative differences between svOCT and histology.

Retinal angiography with real-time speckle variance optical coherence tomography.

This report describes a novel, non-invasive and label-free optical imaging technique, speckle variance optical coherence tomography (svOCT), for visualising blood flow within human retinal capillary networks. This imaging system uses a custom-built swept source OCT system operating at a line rate of 100 kHz. Real-time processing and visualisation is implemented on a consumer grade graphics processing unit. To investigate the quality of microvascular detail acquired with this device we compared images of human capillary networks acquired with svOCT and fluorescein angiography. We found that the density of capillary microvasculature acquired with this svOCT device was visibly greater than fluorescein angiography. We also found that this svOCT device had the capacity to generate en face images of distinct capillary networks that are morphologically comparable with previously published histological studies. Finally, we found that this svOCT device has the ability to non-invasively illustrate the common manifestations of diabetic retinopathy and retinal vascular occlusion. The results of this study suggest that graphics processing unit accelerated svOCT has the potential to non-invasively provide useful quantitative information about human retinal capillary networks. Therefore svOCT may have clinical and research applications for the management of retinal microvascular diseases, which are a major cause of visual morbidity worldwide.

Optical coherence tomography-based measurement of drusen load predicts development of advanced age-related macular degeneration.

PURPOSE: To determine whether baseline drusen load, as measured using spectral-domain optical coherence tomography (SD OCT), is a useful predictor of development of advanced age-related macular degeneration (AMD). DESIGN: Retrospective cohort study. METHODS: setting: Academic clinical practice. study population: All patients with non-neovascular AMD and no retinal pigment epithelial (RPE) atrophy at baseline who were seen between 2007 and 2012 in a single academic retina practice. A minimum of 1 year of follow-up was required. observation: Drusen load (area and volume) was assessed using automated SD OCT software algorithms. main outcome measure: RPE atrophy area, assessed using an automated SD OCT software algorithm, and the development of neovascular AMD. RESULTS: Eighty-three patients met the inclusion criteria with a mean age of 80 years and a mean follow-up time of 2.8 years. Repeated-measures analysis of variance showed an association between drusen area (P = .005) and drusen volume (P = .001) and the development of RPE atrophy. We also found an association between drusen area (P = .001) and drusen volume (P = .001) and the development of neovascular AMD. CONCLUSIONS: Drusen load, as measured using SD OCT, is associated with the development of RPE atrophy and neovascular AMD. SD OCT assessments of drusen load are simple and practical measurements that may be useful in stratifying the risk of developing advanced AMD. These measurements have potential applications in both routine clinical care and clinical trials.

A randomized study comparing the efficacy of bevacizumab and ranibizumab as pre-treatment for pars plana vitrectomy in proliferative diabetic retinopathy.

BACKGROUND AND OBJECTIVE: To compare intravitreal bevacizumab versus ranibizumab as adjuvant treatment prior to pars plana vitrectomy (PPV) in proliferative diabetic retinopathy (PDR) with respect to parameters of surgical complexity. PATIENTS AND METHODS: Prospective, randomized, double-masked pilot study of patients requiring PPV for nonclearing vitreous hemorrhage or tractional retinal detachment (TRD) secondary to PDR. Patients were randomized to receive either intravitreal bevacizumab or ranibizumab at standard doses 1 week preoperatively. Measured parameters included total surgical time, presence of TRD, intraoperative bleeding, iatrogenic retinal breaks, and use of endolaser and endodiathermy or silicone oil. RESULTS: A total of 29 patients were recruited. For surgical parameters, there were no statistically significant differences between the groups in the univariate analyses. Multivariable analysis showed no statistically significant difference for total surgical time. CONCLUSION: This pilot study suggests that intravitreal bevacizumab and ranibizumab are equivalent as surgical adjuvants when used as pre-treatment in patients with PDR undergoing PPV.