Influence of narrow-band ultraviolet B therapy on sirtuin 1 expression in lesional skin of patients with chronic plaque psoriasis: Relation to clinical improvement and interferon-γ expression.

BACKGROUND: Reduced sirtuin 1 (Sirt1) expression in psoriasis was previously reported, and its activation was associated with disease improvement. Narrow-band ultraviolet B (NB-UVB) downregulates several pro-inflammatory cytokines such as interferon-γ (IFN-γ) and influences keratinocyte differentiation in psoriasis. OBJECTIVES: The aim of this study was to study the in vivo influence NB-UVB treatment on Sirt1 expression in psoriatic skin in relation to disease improvement and IFN-γ expression. METHODS: Twenty-six patients with chronic plaque psoriasis were evaluated, and psoriasis area severity index (PASI) was calculated. Skin biopsies were taken from lesional skin of the patients before and after 3 months of treatment with NB-UVB and from 26 controls, where the distribution and immunohistochemistry (IHC) scores of Sirt1 and IFN-γ were determined. RESULTS: After 3 months of treatment, Sirt1 distribution and epidermal IHC score were significantly higher, whereas Sirt1 dermal IHC score and IFN-γ distribution, epidermal and dermal IHC scores were significantly lower than the pre-treatment values. Before and after 3 months of NB-UVB therapy, PASI showed a significant negative correlation with Sirt1 distribution and epidermal IHC score; and a significant positive correlation with interferon-γ distribution and epidermal IHC score. Moreover, Sirt1 distributions were negatively correlated with the corresponding interferon-γ distributions. Conclusions The detected upregulation of epidermal Sirt1 following NB-UVB therapy possibly represents another mechanism by which NB-UVB can act in psoriasis and also highlights the role of Sirt1 upregulation in psoriasis treatment.

Mean macular intercapillary area in eyes with diabetic macular oedema after anti-vascular endothelial growth factor therapy and its association with treatment response.

BACKGROUND: To evaluate the changes in the mean macular intercapillary area (ICA) from sequential enface optical coherence tomography angiography (OCTA) images following intravitreal anti-vascular endothelial growth factor (VEGF) therapy in initially treatment-naïve eyes with diabetic macular oedema (DME). METHODS: In this multicentre retrospective study, 6 × 6 and 3 × 3 mm customised, total retinal projection enface OCTA images were collected and processed for quantitative assessment of ICA by a customised MATLAB software. Measurements were done in concentric regions centred on the fovea-with the exclusion of foveal avascular zone (FAZ)-in 0.5 mm diameter increments as well as within the intervening rings. RESULTS: In this study, 6 × 6 mm OCTA images from 46 eyes of 29 patients, and 3 × 3 mm OCTA images from 23 eyes of 15 patients were included. There was no significant change in mean ICA after treatment in either scan size or in any measurement regions (all p > 0.05). Multivariate analysis revealed that baseline BCVA was significantly correlated with the visual outcome (p = 0.039). Additionally, after correction for age, baseline central retinal thickness (CRT), baseline BCVA, and retinopathy severity, mean ICA in the 1.5 mm circle was found to be a significant predictor of post treatment CRT, (p = 0.006). CONCLUSIONS: Absence of significant change in mean ICA after a minimum of three intravitreal anti-VEGF injections, may indicate that, in the short term, anti-VEGF injections neither impair nor improve macular perfusion in DME. Baseline BCVA was found to be a robust predictor of functional outcome, while inner mean ICA was a significant predictor for macular thickness outcomes.

Intravitreal injections of anti-VEGF agents during COVID-19 pandemic: clinical audit from Tanta University Hospital.

BACKGROUND: The aims of this study were to provide real-life data about the effect of COVID-19 pandemic on the practice of anti-VEGF injections and to evaluate the safety of the modifications in the injection protocol imposed during the ongoing pandemic on the anatomical and functional outcome of patients. METHODS: All patients attending Tanta University hospital for receiving intravitreal anti-VEGF injections were screened. Patients who were previously deferred according to a modified protocol implemented in the hospital in response to the pandemic or who demonstrated deviation from it were included for further analysis. RESULTS: During the audit period, 83 patients attending for anti-VEGF injections were screened, of whom 40 met the abovementioned criteria and were included for analysis. In the deferred subgroup (11 eyes), predeferral mean values of logMAR best corrected visual acuity (BCVA) and central retinal subfield thickness (CST) were 1 ± 0.23 and 444.57 ± 200.1 µm, respectively. There was no significant change when the patients returned for their deferred injections, with the mean BCVA and CST values being 0.8 ± 0.22 and 413.71 ± 237.7 µm, respectively (p = 0.27 and p = 0.12). Moreover, 29 patients encountered a disturbed injection schedule, particularly skipping their injection appointments due to infection fear as found in 18 patients. CONCLUSION: The COVID-19 pandemic has imposed pressing challenges in maintaining essential health care while ensuring the prevention of spread of infection. Although the modified injection protocol confirmed to be safe for patients, the pandemic caused deflection from the optimum practice in the form of successive skipping of appointments and delays in the processing of patient injection schedules.

Effects of enhanced depth imaging and en face averaging on optical coherence tomography angiography image quantification.

PURPOSE: To examine the effects of enhanced depth imaging (EDI) and en face averaging on global vascular measurements of optical coherence tomography angiography (OCTA) images. METHODS: All eyes were imaged with 3 mm × 3 mm fields centered at the fovea using the Carl Zeiss Cirrus 5000 spectral-domain OCTA, with and without EDI, and the Zeiss PLEX Elite 9000 swept-source OCTA. Vessel area density (VAD), vessel length (VL), and vessel diameter index (VDI) were calculated for the superficial capillary plexus (SCP) en face angiograms. For the choriocapillaris (CC), VAD and the number, total area, and average size of flow voids were calculated. These metrics were compared between SD- and SS-OCTA images, with and without en face averaging and EDI. RESULTS: Both averaging and EDI had a significant effect on quantitative metrics. EDI images trended toward a decrease in SCP VAD. In the CC, EDI decreased average flow void size. Averaging increased CC VAD while decreasing number of flow voids, total flow void area, and average flow void size. With both averaging and EDI, SD-OCTA was not able to visualize as many CC flow voids, particularly of a smaller size, compared with SS-OCTA. CONCLUSIONS: Averaging and EDI affect quantitative metrics from SCP and CC OCTA images. EDI resulted in a trend toward decreased VAD in SCP images. Averaging had a major effect on CC imaging. Even with the combination of EDI and en face averaging, SD-OCTA images do not appear to approximate SS-OCTA images in terms of quantitative metrics. This has implications for clinical and research use of SD-OCTA for retinal imaging.

DISTINGUISHING INTRARETINAL MICROVASCULAR ABNORMALITIES FROM RETINAL NEOVASCULARIZATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: With the increasing prevalence of diabetes, fast, noninvasive identification of proliferative diabetic retinopathy (PDR) becomes essential. This study evaluated the utility of optical coherence tomography angiography (OCTA) to characterize intraretinal microvascular abnormalities (IRMA) and retinal neovascularization (NV). METHODS: Patients with severe non-PDR or PDR were imaged with fluorescein angiography and widefield swept-source OCTA (Zeiss Plex Elite 9000; Carl Zeiss Meditec, Dublin, CA). Regions suspicious for IRMA or retinal NV were identified and the OCTA, including flow overlay on the co-registered structural optical coherence tomography, and fluorescein angiography images were graded by two masked readers. RESULTS: Ninety-six foci of irregular vasculature were analyzed, comprised of 70 IRMA and 26 retinal NV lesions from 14 eyes. Compared with fluorescein angiography, OCTA with flow overlay demonstrated specificity of 99% and sensitivity of 92% in identifying IRMA and NV. Neovascularization differed from IRMA on OCTA by demonstrating supraretinal flow breaching the internal limiting membrane and posterior hyaloid (P < 0.001). Intraretinal microvascular abnormalities were distinguished from NV by outpouching of the internal limiting membrane (P = 0.035). Vascular flow was reduced in the presence of fibrosis. CONCLUSION: Optical coherence tomography angiography, through flow overlay, has utility to image and differentiate IRMA and NV, which are key features distinguishing severe non-PDR and PDR, respectively. Noninvasive widefield OCTA may be a useful tool to diagnose high-risk diabetic retinopathy eyes.

Optical coherence tomography angiography analysis of macular vessel density before and after anti-VEGF therapy in eyes with diabetic retinopathy.

PURPOSE: To evaluate changes in macular vessel density following intravitreal anti-VEGF injection in patients with diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). METHODS: In this retrospective case series, optical coherence tomography angiography (OCTA) images from 55 eyes of 35 patients with either DME (46 eyes) or PDR (9 eyes) were included. Macular capillary vessel density at the level of the superficial retinal capillary plexus (SCP), deep retinal capillary plexus (DCP) and total retinal capillary plexus (TCP) before and after anti-VEGF treatment was calculated. Longitudinal changes in vessel density following serial anti-VEGF treatment were analyzed in a subset of eyes. RESULTS: Vessel density in the SCP, DCP or TCP was not found to be significantly different after one, two or three intravitreal injections (p > 0.05 for all time points). Subgroup analysis revealed no significant change in the DME and PDR subgroups (all p > 0.05). Multivariate analysis revealed no effect of type of injected anti-VEGF agent or presence of previous treatment on VD measurements (all p > 0.05). There was no correlation between the anatomic response of DME to treatment and VD measurements. CONCLUSIONS: In this study, macular vessel density remained statistically unchanged following up to three intravitreal injections of any anti-VEGF agent. This indicates that there may not be an early effect of anti-VEGF treatment on macular vessel density and its effect on macular perfusion may not be a direct change in microvascular flow.

Histopathology and electron microscopy evaluation of the sildenafil effect on diabetic rats' retinae.

PURPOSE: Although there is increasing evidence that phosphodiesterase-5 (PDE-5) inhibitors modify the effect of diabetes on different tissues, its effect on diabetic retinopathy is not well studied. METHODS: Forty male Sprague-Dawley (SD) rats were divided into four groups: group I = control group that received no treatment; group II (diabetic group), in which diabetes was induced by a single streptozotocin injection; group III (sildenafil small dose, SSD), in which diabetes was similarly introduced (however, rats received daily oral 1 mg/kg sildenafil citrate (SC) for 3 months); and group IV (sildenafil large dose, SLD), which was as in group 3, but SC was 2.5 mg/kg. After 3 months, globes were removed and retinae were dissected; one globe from each rat was examined by light microscopy (LM), and the other by electron microscopy (EM). RESULTS: In contrast to the control group, diabetic rats in group II demonstrated well-established diabetic changes in the form of capillary congestion, decreased cell population, hyaline changes of capillary walls, and degenerated nerve fiber layer by LM. Similarly, EM demonstrated photoreceptor degeneration, mitochondrial cristolysis, and vacuolated depleted cells among other features in group II. These diabetic features were less prominent in group III and nearly absent in group IV. CONCLUSION: SC use in the early stages of DR may prevent/delay diabetic retinopathy development or progression in diabetic rat models, an effect that seems to be dose-related.

Chronic sildenafil citrate use decreases retinal vascular endothelial growth factor expression in diabetic rats: a pilot study.

BACKGROUND: Sildenafil citrate (SC) attenuates endothelial dysfunction. However, its effects on diabetic retinopathy (DR), which is mainly a microvascular disease, remain unclear. Vascular endothelial growth factor (VEGF) is known to be a critical mediator of DR. Therefore, we investigated the effects of SC on diabetic retina by measuring VEGF levels. METHODS: In this study, twenty-eight rats were divided into the following groups: group I, the control group; group II, rats with streptozotocin-induced diabetes; group III, rats with streptozotocin-induced diabetes receiving daily oral sildenafil at 1 mg/kg; and group IV, rats with streptozotocin-induced diabetes receiving high-dose daily sildenafil at 2.5 mg/kg. After 3 months, VEGF was measured in the retina specimen in one eye and the vitreous body in the other eye by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. RESULTS: We found that VEGF expression in the retina was low in all rats from groups I and IV and in 30% of rats from group III; 80% of rats in group II demonstrated high VEGF expression in the retinae (P < 0.001). VEGF concentrations in the vitreous body samples were 32 ± 2, 61 ± 4, 44 ± 5, and 36 ± 3 pg/l in groups I-IV, respectively (P < 0.001). CONCLUSION: VEGF decreased significantly in the eyes of diabetic rats after chronic oral sildenafil citrate treatment. SC may have a modifying/attenuating effect on DR. However, further studies are needed to evaluate its use as an adjunctive treatment.

Persistent diabetic macular edema: Definition, incidence, biomarkers, and treatment methods.

Intravitreal antivascular endothelial growth factor (anti-VEGF) treatment has drastically improved the visual and anatomical outcomes in patients with diabetic macular edema (DME); however, success is not always guaranteed, and a proportion of these eyes demonstrate persistent DME (pDME) despite intensive treatment. While standardized criteria to define these treatment-resistant eyes have not yet been established, many studies refer to eyes with no clinical response or an unsatisfactory partial response as having pDME. A patient is considered to have pDME if the retinal thickness improves less than 10-25% after 6 months of treatment. A range of treatment options have been recommended for eyes with pDME, including switching anti-VEGF agents, using corticosteroids and/or antioxidant drugs in adjunct with anti-VEGF therapy, and vitrectomy. In addition, multimodal imaging of DME eyes may be advantageous in predicting the responsiveness to treatment; this is beneficial when initiating alternative therapies. We explore the literature on persistent DME regarding its defining criteria, incidence, the baseline biological markers that may be useful in anticipating the response to treatment, and the available treatment options.

Evaluation of Urgent Retinal Practice and Safety Measures for Physicians and Patients During COVID-19 Pandemic.

Purpose: To assess the impact of the COVID-19 pandemic on urgent retina practice and factors influencing adherence of physicians and patients to safety measures. Methods: In this clinical audit, urgent or emergent vitreoretinal surgical disorders that presented to our hospital during the period of 15th March-15th May 2020 were compared with the period just before the pandemic declaration (15th December 2019-15th February 2020). Additionally, two questionnaires assessing the adherence to safety measures were circulated to the medical personnel and a sample of patients. The collected data were analyzed, and accordingly, recommendations were proposed to the hospital administration and specific corrective measures were applied. The outcome of applying these corrective measures was assessed in the re-audit cycle during the period of 15th June-15th August 2020. Results: There was a significant decrease in the number of urgent or emergent vitreoretinal surgical disorders that presented to our hospital during the pandemic (161 versus 302 cases in a similar period before the pandemic; p = 0.022). Just with the pandemic recession, there was a significant increase in the number of urgent cases (391 versus 161 cases during the pandemic; p = 0.006), also there was an increased number of complex cases. Residents and fellows were less compliant than attending physicians in adherence to safety measures. Conclusion: Delayed presentation of urgent retinal cases during the pandemic highlights the importance of public awareness of urgent conditions that need immediate medical or surgical care. Attention to young physicians during the pandemic is crucial as they are less adherent to safety measures due to work overload.

Optical Coherence Tomography Angiography Biomarkers Predict Anatomical Response to Bevacizumab in Diabetic Macular Edema.

PURPOSE: To identify biomarkers that may predict an early anatomical response to the treatment of diabetic macular edema (DME) with intravitreal bevacizumab (IVB) by means of optical coherence tomography angiography (OCTA). METHODS: This study is a retrospective study of treatment-naïve patients with DME who underwent 6 × 6 mm OCTA imaging of the macula at baseline and after three monthly IVB injections. Thirty-six eyes of 23 patients were included. Eyes that demonstrated evidence of an early anatomical response, consisting of a >10% decrease in central macular thickness (CMT) (n = 18), were compared with those eyes that failed to show such an improvement (n = 18). RESULTS: At baseline, early-response eyes had worse starting best-corrected visual acuity (BCVA, LogMAR 0.84 ± 0.41 versus LogMAR 0.51 ± 0.15, p = 0.004) and a larger CMT (490 ± 135 µm versus 356 ± 33 µm, p = 0.001), but smaller foveal avascular zones (FAZ) (0.309 ± 0.098mm versus 0.413 ± 0.095 mm, p = 0.003) compared with eyes that proved refractory to three monthly injections of IVB. The vascular density (VD) in both the foveal superficial and deep capillary plexuses was significantly greater in eyes that showed an early-treatment response compared with eyes that were non-responders (24.86 ± 6.90% versus 19.98 ± 7.13%, p = 0.045 and 32.30 ± 4.88% versus 26.95 ± 7.25%, p = 0.028, respectively). Early-treatment response to IVB was predicted by starting CMT (r 2= 0.266, p = 0.001), FAZ size (r 2= 0.234, p = 0.003), and VD in the superficial parafovea (r 2= 0.217, p = 0.004) and deep fovea (r 2= 0.157, p = 0.037). CONCLUSION: Projection-resolved OCTA may be useful in predicting an early anatomical response of DME to treatment with IVB.

Incidence and Risk Factors for Retinopathy of Prematurity (ROP) in Biggest Neonatal Intensive Care Unit in Itay Elbaroud City, Behera Province, Egypt.

AIM OF THE WORK: To evaluate the incidence and risk factors for development of retinopathy of prematurity (ROP) in the biggest neonatal intensive care unit (NICU) in Itay Elbaroud City, Behera province, Egypt. METHODS: We studied data of 240 newly born infants with gestational age (GA) ≤34 weeks or birth weight (BW) ≤2000 g or infants with unstable course who were admitted to the biggest NICU in Itay Elbaroud City, Behera province, Egypt, between October 1, 2018 and October 31, 2020. There is no standard screening system in Egypt. Furthermore, we had screened babies more than 1500 g, more than 32 weeks and found signs of ROP, so we decided to expand our inclusion criteria to include babies up to 2000 g of birth weight and up to 34 weeks gestational age in addition to older and heavier babies with unstable course in NICUs. Clinical information about perinatal neonates was collected by reviewing medical charts. The main outcomes are the incidence and severity of ROP. The relationship of clinical risk factors and the development of ROP were analyzed. RESULTS: The overall incidence of ROP was 34.1%, and the overall incidence of type 1 ROP was 26.3% of infants. ROP was significantly associated with GA (odds ratio; OR: 6.8; (3.7-12.3), BW (OR: 4.1; 2.3-7.3), apnea, supplementary oxygen administration, and thrombocytopenia. CONCLUSION: The incidence of ROP is high in Itay Elbaroud city, Behera Province, Egypt. Immaturity, low birth weight, low gestational age, oxygen administration, apnea, thrombocytopenia, and jaundice are important risk factors for development of ROP.

Trichoscopic signs of tinea capitis: a guide for selection of appropriate antifungal.

BACKGROUND: Tinea capitis is the most common pediatric dermatophyte infection. Optimal treatment regimen differs according to the type of the dermatophyte involved. OBJECTIVES: The aim of this work was to study the trichoscopic signs in relation to isolated organism in a sample of Egyptian patients with tinea capitis and the possibility of using them as a guide for selection of appropriate antifungal. METHODS: This study was carried out on 60 subjects with tinea capitis. Patients were mycologically examined, both direct microscopy with KOH preparation and culture of the scraped hair materials on Sabouraud dextrose agar. Culture mounts were used for identification of the organism. Trichoscopic examination of all patients was performed using the Dermlite DLIII dermoscope. RESULTS: There was significant higher prevalence of both comma and corkscrew hair in endothrix infection and T. violaceum-infected cases. On the other hand, there was significant higher prevalence of zigzag, barcode hairs, and white sheaths in ectothrix infection and M. canis-infected cases. CONCLUSION: While some trichoscopic findings are nonspecific, others were found to be more specific. Finding zigzag hairs and barcode hairs points to ectothrix infection (M. canis), and it is recommended to start treatment with griseofulvin. On the other hand, finding comma hairs and corkscrew hairs without zigzag hairs and barcode hairs points to endothrix infection (T. violaceum), and it is recommended to start treatment with terbinafine in the usual dose.

Differential Modulation of Autophagy Contributes to the Protective Effects of Resveratrol and Co-Enzyme Q10 in Photoaged Mice.

BACKGROUND: In photoaging, the accumulation of ultraviolet (UV)-induced oxidative damage leads to the characteristic hallmarks of aging. Here arises the importance of autophagy as a cellular degradation process that cleans the cells of defective or aged organelles and macromolecules, thus maintaining cellular homeostasis. In spite of this, the exact impact of autophagy in photoaging is still elusive. OBJECTIVE: To evaluate the protective effects of resveratrol and/or co-enzyme-Q10 against the UVA-induced alterations and to explore the role of autophagy in their proposed benefits. METHODS: Sixty female mice were randomly divided into normal control, untreated UVA-exposed, resveratrol (50mg/kg), co-enzyme-Q10 (100mg/kg), and resveratrol/co-enzyme-Q10-treated UVA-- exposed groups. Clinical signs of photoaging were evaluated using a modified grading score and the pinch test. Skin malondialdehyde and reduced glutathione were assessed as markers of oxidative stress. Tissues were examined for histopathological signs of photodamage, and autophagic changes were determined by immunohistochemical detection of LC3 and P62 in the different cells of the skin. RESULTS: UVA-exposure increased the oxidative stress with subsequent epidermal and dermal injury. This was associated with the stimulation of autophagy in the keratinocytes and inhibition of autophagic flux in the fibroblasts and infiltrating macrophages. Both drugs corrected the impaired pinch test, macro-and microscopic changes, and exhibited distinct staining patterns with anti-LC3 and P62 in the different cell types denoting autophagic modulation. CONCLUSION: Changes in autophagic flux are strongly implicated in photoaging associated skin damage and the differential modulation of autophagy by resveratrol and, to a lesser extent by Co-enzyme- Q10, is partially involved in their therapeutic benefits.

Visual and anatomic outcomes of sustained single agent anti-VEGF treatment versus double anti-VEGF switching in the treatment of persistent diabetic macular edema.

BACKGROUND: To compare the anatomical and visual outcomes in eyes with persistent diabetic macular edema (DME) after initial anti-VEGF therapy that were retreated continuously with the same anti-VEGF drug versus those that underwent two successive cycles of medication change in anti-VEGF drugs (double anti-VEGF switch). METHODS: Retrospective review of eyes with persistent DME after 3 initial consecutive monthly anti-VEGF injections. This cohort was divided into two groups: Group 1 continued to receive the same initial anti-VEGF drug for at least 18 months while group 2 eyes were switched to different anti-VEGF medications twice. Group 1 was further subdivided into: Group 1A composed of eyes with less than 20% reduction in central subfield thickness (CRT) at month 3; and group 1B eyes with greater than or equal to 20% reduction in CRT. The percentage of eyes that achieved greater than 10 letters visual acuity (VA) gain or loss was recorded as the primary end point (through month 18 in group 1 and month 6 after 2nd switch in group 2). RESULTS: Group 1A, 1B and group 2 were composed of 24, 18, and 14 eyes respectively. 34.7%, 56.2% and 36.3% of eyes achieved > 10 letters gain, while 4.3%, 6.2% and 27.2% of eyes lost > 10 letters in groups 1A, 1B, and 2, respectively. Analysis of the visual acuity (VA) letter change in this time interval revealed no significant difference between all groups (p = 0.11). Mean VA and CRT measurements at the primary endpoint in all groups were 0.5, 0.39, and 0.47 logMAR (p = 0.44), and 369.7, 279.9, 321 µm, (p = 0.01) respectively. CONCLUSIONS: There was no difference in the visual outcomes between the two treatment strategies in eyes with persistent DME after 3 consecutive anti-VEGF injections. This may indicate that anti-VEGF switching-even if it is done twice-may have comparable clinical outcomes to sustained treatment with one agent.

Morphological changes in intraretinal microvascular abnormalities after anti-VEGF therapy visualized on optical coherence tomography angiography.

BACKGROUND: To examine the baseline morphological characteristics and alterations in intraretinal microvascular abnormalities (IRMAs) in response to anti-vascular endothelial growth factor (anti-VEGF) treatment, documented by optical coherence tomography angiography (OCTA) in diabetic eyes. METHODS: In this retrospective study, IRMAs were evaluated with multimodal imaging (fundus photography, fluorescein angiography, OCTA) in treatment-naïve diabetic eyes before and after anti-VEGF treatment for diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR) and compared to diabetic control eyes with similar diabetic retinopathy (DR) severity that did not receive anti-VEGF therapy. The morphological characteristics of IRMAs on enface OCTA imaging were graded by masked readers at baseline, then after anti-VEGF therapy in treated eyes or after observation in control eyes. Characterization of interval changes in an IRMA were based on the following parameters: branching, vessel caliber and area of adjacent capillary non-perfusion. RESULTS: The treated group included 45 IRMA foci from 15 eyes of 11 patients, while the control group included 27 IRMA foci from 15 eyes of 14 patients. Following anti-VEGF treatment, enface OCTA demonstrated that 14 foci of IRMA (31%) demonstrated regression with normalization of appearance of the capillary bed, 20 IRMAs (44%) remained unchanged, six IRMAs (13%) progressed with enlargement or development of new IRMAs and five IRMAs (11%) demonstrated complete obliteration defined as IRMA disappearance with advancing capillary drop-out. In the control group, 17 IRMA (63%) remained stable, 8 IRMAs (29.6%) progressed and 2 experienced total obliteration (7.4%). The difference in rank order between the two groups was statistically significant (p = 0.022). CONCLUSIONS: In eyes with DR status post anti-VEGF therapy, foci of IRMAs have a variable course demonstrating one of four possible outcomes: regression, stability, progression or complete obliteration. In contrast, none of the untreated control diabetic eyes demonstrated regression of IRMAs, consistent with known progression of DR severity in high risk eyes. Morphologic evaluation of IRMAs with OCTA may help to monitor changes in retinal blood flow as well as the response to anti-VEGF treatment.

Topographic analysis of macular choriocapillaris flow deficits in diabetic retinopathy using swept-source optical coherence tomography angiography.

BACKGROUND: The purpose of this study was to investigate the association between diabetic retinopathy (DR) severity and macular choriocapillaris (CC) flow deficit percentage (FD %) in different macular regions using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: Diabetic patients with SS-OCTA images were graded by severity and retrospectively assessed. CC FD % was calculated in four different regions of the OCTA image: inner, middle, outer, and full-field region. The generalized estimating equations (GEE) approach for clustered eye data was used to determine effect size and significance of age and disease severity on FD % for each region. RESULTS: 160 eyes from 90 total diabetic patients met inclusion criteria. Out of 90 patients, 33 had no DR, 17 had mild nonproliferative DR (NPDR), 8 had moderate NPDR, 10 had severe NPDR and 22 had proliferative DR. Age and DR severity had a significant positive association with FD % for each region studied with a greater effect in the two centermost regions. The increase in flow deficit percentage per year of age by region was: inner 0.12 (p < 0.001), middle 0.09 (p < 0.001), outer 0.05 (p < 0.001, full-field 0.06 (p < 0.001). The increase in flow deficit percentage per increase in diabetic retinopathy severity stage by region was: inner 0.65 (p < 0.0087), middle 0.56 (p < 0.0012), outer 0.33 (p < 0.045), full-field 0.36 (p < 0.018). CONCLUSIONS: Topographic analysis of the CC FD % in diabetic eyes suggests that CC flow impairment corresponds to DR severity, with all studied regions of the CC significantly affected. There was greater regional impairment due to age and disease severity in the inner and middle regions.

Accuracy and Reliability in Differentiating Retinal Arteries and Veins Using Widefield En Face OCT Angiography.

PURPOSE: To evaluate the accuracy and reliability in differentiating retinal arteries from veins using widefield optical coherence tomography angiography (OCTA). METHODS: Ten healthy eyes and 12 eyes from diabetic patients were included. Foveal-centered swept-source OCTA images (12 × 12 mm) were obtained using the PLEX Elite 9000. Vessels were graded as arteries or veins by two independent, masked readers. Arteriovenous crossings were also evaluated in healthy eyes. The vessel identification gold standard was defined using color fundus photographs (CFP) for normal eyes and both CFP and fluorescein angiography for diabetic eyes. Grading accuracy was compared to the gold standard and reliability between readers assessed. RESULTS: The study evaluated 538 vessels (119 first order, 110 second, 309 third) in healthy eyes and 645 vessels (184 first order, 159 second, 302 third). In healthy eyes, the average accuracies identifying all, first-, second-, and third-order vessels were 98.61%, 99.16%, 100%, and 98.06%, respectively. Cohen's κ between graders in all vessels was 0.948. In diabetic eyes, the average accuracies identifying vessels were 96.90%, 99.46%, 97.77%, and 94.85%, respectively. Cohen's κ between graders for all vessels was 0.888. For crossing identification, the average accuracy and Cohen's κ were low (60.71% and 0.659, respectively). CONCLUSIONS: En face OCTA allows for accurate and reliable artery and vein identification; for small branches and crossings, identification by en face OCTA alone may be less accurate and reliable. TRANSLATIONAL RELEVANCE: Arteries and veins can be differentiated on OCTA, assisting in clinically identifying pathology as arterial or venous side.

Impact of Binarization Thresholding and Brightness/Contrast Adjustment Methodology on Optical Coherence Tomography Angiography Image Quantification.

PURPOSE: Binarization is a critical technique in optical coherence tomography angiography (OCTA) image analysis, but there is no consistency in the method used in published OCTA studies. This study assessed whether differences in OCTA binarization and brightness and contrast adjustments affect quantification measurements. DESIGN: Prospective cross-sectional validity study. METHODS: This was a single-center study examining 21 eyes of 11 healthy individuals. All eyes were imaged using a swept-source OCTA (Zeiss), and quantitative measurements resulting from five binarization thresholding and five brightness/contrast adjustment methods were compared. All measurements were calculated for the superficial plexus and choriocapillaris (CC), as well as unaveraged and averaged en face OCTA images. RESULTS: There were statistically significant differences between measurements from different binarization thresholding methods (P < 0.0001), as well as measurements from different histogram adjustments (P < 0.0001). The binarization thresholds yielded different measurements when combined with variable brightness/contrast adjustments. The method of analysis also affected the directionality of trends in imaging measurements between unaveraged and averaged CC images. CONCLUSIONS: The method of OCTA image binarization thresholding and histogram adjustment significantly alters quantitative measurements and the directionality of trends. Results obtained from different OCTA binarization methods should be seen as valid only for that given method. This has significant consequences for clinical trials using OCTA measurements as outcome measurements. A consensus is needed across the research community for a consistent method for OCTA image quantification and greater attention paid to fully describing methods in published studies.

Global Analysis of Macular Choriocapillaris Perfusion in Dry Age-Related Macular Degeneration using Swept-Source Optical Coherence Tomography Angiography.

Purpose: Swept-source optical coherence tomography angiography (SS-OCTA) was used to investigate if the clinical stage of dry age-related macular degeneration (AMD) was correlated with global and regional macular choriocapillaris (CC) perfusion. Methods: In this retrospective, cross-sectional study, 6 × 6-mm SS-OCTA images from eyes with early, intermediate, and advanced dry AMD (56 eyes, 41 patients) were analyzed using algorithms described in the literature to assess regional flow deficit percentage (FD%) and average flow deficit size. Regions were defined by concentric areas centered on the fovea: a 1-mm-diameter area, 3-mm-diameter ring, 5-mm-diameter area, 5-mm-diameter ring, and 6 × 6-mm whole image. Data were modeled using the generalized estimating equations approach. Results: The relationship between age and CC FD% and average flow deficit size was statistically significant (P ≤ 0.05) in all regions of analysis by linear modeling. The relationship between dry AMD stage and FD% was statistically significant by linear modeling in the 5-mm ring, and between dry AMD stage and average flow deficit size in the 3-mm ring, 5-mm area, 5-mm ring, and 6 × 6-mm whole image. Conclusions: Linear modeling suggests a statistically significant relationship between dry AMD stage and CC perfusion, most prominent in the more peripheral regions of the macula.