C-reactive protein-complement factor H axis as a biomarker of activity in early and intermediate age-related macular degeneration.

Purpose: To determine and compare the serum levels of complement Factor H (FH), monomeric C-Reactive Protein (mCRP) and pentameric C-Reactive protein (pCRP) in patients with age-related macular degeneration (AMD) and to correlate them with clinical, structural and functional parameters. Methods: Cross-sectional observational study. One hundred thirty-nine individuals (88 patients and 51 healthy controls) from two referral centers were included and classified into three groups: early or intermediate AMD (n=33), advanced AMD (n=55), and age and sex matched healthy controls (n=51). Serum levels of FH, mCRP, and pCRP were determined and correlated with clinical and imaging parameters. Results: Patients with intermediate AMD presented FH levels significantly lower than controls [186.5 (72.1-931.8) µg/mL vs 415.2 (106.1-1962.2) µg/mL; p=0.039] and FH levels <200 µg/mL were associated with the presence of drusen and pigmentary changes in the fundoscopy (p=0.002). While no differences were observed in pCRP and mCRP levels, and mCRP was only detected in less than 15% of the included participants, women had a significantly higher detection rate of mCRP than men (21.0% vs. 3.8%, p=0.045). In addition, the ratio mCRP/FH (log) was significantly lower in the control group compared to intermediate AMD (p=0.031). Visual acuity (p<0.001), macular volume (p<0.001), and foveal thickness (p=0.034) were significantly lower in the advanced AMD group, and choroidal thickness was significantly lower in advanced AMD compared to early/intermediate AMD (p=0.023). Conclusion: Intermediate AMD was associated in our cohort with decreased serum FH levels together with increased serum mCRP/FH ratio. All these objective serum biomarkers may suggest an underlying systemic inflammatory process in early/intermediate AMD patients.

Vitrectomized vs non-vitrectomized eyes in DEX implant treatment for DMO-Is there any difference? the VITDEX study.

OBJECTIVE: We aimed to compare visual and anatomical outcome in vitrectomized and non-vitrectomized eyes treated with dexamethasone (DEX) implant due to diabetic macular oedema (DMO). DESIGN: Multicenter, retrospective, interventional study. PARTICIPANTS: 236 eyes from 234 patients with DMO with or without previous vitrectomy performed with follow-up of 12 months. METHODS: Records were reviewed for cases of DMO treated with DEX implant in vitrectomized and not vitrectomized eyes. Best corrected visual acuity (BCVA), central subfoveal thickness (CST), and intraocular pressure (IOP) were recorded at baseline and 12 months after treatment with DEX implants. Correlations between vitreous status and visual and anatomical outcome, as well as safety profile were analysed. MAIN OUTCOME MEASURES: BCVA and CST over follow-up period. SECONDARY OUTCOMES: cataract rate formation, intraocular pressure increase, number of implants needed. RESULTS: The non-vitrectomized group included 130 eyes (55.1%), the vitrectomized group included 106 eyes (44.9%). The groups were well balanced for age and gender (p = 0.540, and p = 0.053, respectively). Both groups showed statistically significant improvement in BCVA and CST (for all groups: p < 0.001). There was no significant difference between the groups in terms of change in vision (p = 0.89) and anatomy (p = 0.65). The mean number of DEX implants given during follow-up was 3.5 in both groups, and there was no significant difference between the groups (p = 0.81). CONCLUSION: We demonstrated similar anatomical and functional efficacy of DEX implant in non-vitrectomized and vitrectomized eyes. Its efficacy was not influenced by full vitrectomy for diabetic retinopathy complications. Safety profile was well balanced between groups.

Polypoidal Choroidal Vasculopathy Based on Non-ICGA Criteria in White Patients With Neovascular Age-Related Macular Degeneration.

PURPOSE: To determine prevalence of probable polypoidal choroidal vasculopathy (PCV) among White patients with neovascular age-related macular degeneration (nAMD) using non-indocyanine green angiography (ICGA) criteria DESIGN: Multicenter, multinational, retrospective, cross-sectional study. METHODS: A total of 208 treatment-naive eyes from Hispanic and non-Hispanic White individuals diagnosed with nAMD were included. All underwent color fundus photography (CFP), optical coherence tomography (OCT), and fluorescein angiography (FFA). De-identified images of study eyes were sent to 2 groups of graders. Group 1 reviewed CFP, OCT, and FFA to confirm nAMD diagnosis. Group 2 reviewed CFP and OCT to determine highly suggestive features for PCV. Probable PCV diagnosis defined as the presence of ≥2 of 4 highly suggestive features for PCV: notched or fibrovascular pigment epithelial detachment (PED) on CFP, sharply-peaked PED, notched PED, and hyperreflective ring on OCT. RESULTS: Eleven eyes were excluded because of poor image quality (6) or non-nAMD diagnosis (5). Of 197 eligible eyes (197 patients), the mean age (SD) was 78.8 years (8.9), 44.2% were men, 26.4% were Hispanic, and 73.6% were non-Hispanic White individuals; 41.1%, 23.4%, 9.1%, and 2.5% had ≥1, ≥2, ≥3, and 4 highly suggestive features. Results showed that 23.4% (95% CI, 17.6%-29.9%) had probable PCV diagnosis. Predominantly occult CNV was more frequently found in probable PCV than nAMD subgroup (84.8% vs 64.9%, P = .01). Hispanic White individuals had a lower prevalence of probable PCV than non-Hispanic White individuals (9.6% vs 28.2%, P = .006) CONCLUSIONS: These findings suggest that probable PCV occurs between 17.6% and 29.9% in White individuals with nAMD, and more commonly in non-Hispanic than in Hispanic White individuals.

Optical Coherence Tomography Angiography in Type 1 Diabetes Mellitus. Report 4: Glycated Haemoglobin.

The purpose of this study was to evaluate specifically the relationship between glycated haemoglobin (HbA1c) levels and retinal optical coherence tomography (OCT) and OCT angiography (OCTA) parameters in type 1 Diabetes Mellitus (DM). A total of 478 type 1 DM patients and 115 controls were included in a prospective OCTA trial (ClinicalTrials.gov NCT03422965). Subgroup analysis was performed for controls, no diabetic retinopathy (DM-no DR) and DR patients (DM-DR), and HbA1c levels. OCT and OCTA measurements were compared with HbA1c levels (current and previous 5 years). DM-no DR patients with HbA1c levels >7.5% showed lower VD than DM-DR and controls (20.16 vs. 20.22 vs. 20.71, p < 0.05), and showed a significant correlation between HbA1c levels and FAZc (p = 0.04), after adjusting for age, gender, signal strength index, axial length, and DM disease duration. DM-DR patients with HbA1c > 7.5% presented greater CRT than DM-no DR and controls (270.8 vs. 260 vs. 251.1, p < 0.05) and showed a significant correlation between HbA1c and CRT (p = 0.03). In conclusion, greater levels of HbA1c are associated with OCTA changes in DM-no DR patients, and with structural OCT changes in DM-DR patients. The combination of OCTA and OCT measurements and HbA1c levels may be helpful to identify patients at risk of progression to greater stages of the diabetic microvascular disease.

Systemic contribution of inflammatory mediators to the severity of diabetic and uveitic macular edema.

PURPOSE: To assess whether serum cytokine and growth factor levels are associated with diabetic macular edema (DME) and uveitic macular edema (UME) objective severity. METHODS: Cross-sectional observational study of 81 patients (1 eye/patient) with DME (n=48) and UME (n=33). Macular edema (ME) was defined upon central macular thickness (CMT) ≥ 300 µm on spectral domain optical coherence tomography (OCT). Serum samples were obtained from peripheral blood and IL-1ß, IL-6, IL-8, IL-10, MCP-1, TNF-α, and VEGF levels were determined by Luminex analysis. Main outcome measure was the correlation between mediators' levels and CMT and macular volume (MV) on OCT for ME cases. RESULTS: In DME, IL-6 levels were found to significantly correlate with MV (r=0.324; p=0.028) whereas in UME, IL-8 was significantly associated with both CMT (r=0.401; p=0.021) and MV (r=0.391; p=0.024). IL-8 independently correlated with CMT (ß=177.2; p=0.033) and MV (ß=3.17; p=0.008) in UME multivariate model. CONCLUSION: Peripheral blood IL-6 and IL-8 levels could play a role in the severity of DME and UME, respectively. IL-8 even seems to be independently associated with CMT and MV in UME cases. Such systemic implications could enforce DME and UME personalized diagnostic and therapeutic approaches.

GRAding of functional and anatomical response to DExamethasone implant in patients with Diabetic Macular Edema: GRADE-DME Study.

To analyze functional and anatomical response patterns to dexamethasone (DEX) implant in diabetic macular edema (DME), to describe proportion of responders and non-responders, and to propose a new DME grading system. Retrospective, multicenter, observational cohort study. Naïve and non-naïve DME patients were treated with DEX, with visual acuity (VA) ≥ 0.2 logMAR and central subfield thickness (CST) of ≥ 300 µm. Functional and anatomical responses were graded after 2 and 4 months, and categorized as early and stable improvement, early and progressive improvement, pendular response, delayed improvement, and persistent non-response. 417 eyes were included (175 treatment naïve eyes). Compared to non-naïve eyes, naïve eyes showed a very good functional response (VA gain ≥ 10 letters) more frequently after 2 and 4 months (56% and 57% [naïve] vs. 33% and 28% [non-naïve], p < 0.001). A VA gain < 5 letters (non-response) after 2 and 4 months was seen in 18% and 16% of naïve eyes, and in 49% and 53% of non-naïve eyes (p < 0.001). A lack of anatomical response was rare in both groups, but more frequently in non-naïve eyes (12% vs. 4%, p = 0.003). Functionally and anatomically, naïve eyes showed most frequently an early and stable improvement (functionally: 77/175 44%; anatomically: 123/175 eyes, 70%). Most non-naïve eyes experienced no significant improvement functionally (97/242 eyes, 40%), despite a mostly early and stable improvement anatomical response pattern (102/242 eyes, 42%). Functional but not anatomical response patterns were influenced by baseline VA. Naïve and non-naïve eyes show different functional and anatomical response patterns to DEX implant. Functional non-responders are rare in naïve eyes, whereas anatomical non-response is unusual in both groups.

Optical Coherence Tomography Angiography in Type 1 Diabetes Mellitus-Report 2: Diabetic Kidney Disease.

The purpose of this study is to investigate potential associations between optical coherence tomography angiography (OCTA) parameters and diabetic kidney disease (DKD) categories in type 1 diabetes mellitus (T1DM) patients and controls. A complete ocular and systemic examination, including OCTA imaging tests and bloods, was performed. OCTA parameters included vessel density (VD), perfusion density (PD), foveal avascular zone area (FAZa), perimeter (FAZp) and circularity (FAZc) in the superficial vascular plexus, and DKD categories were defined according to glomerular filtration rate (GFR), albumin-creatinine ratio (ACR) and KDIGO prognosis risk classifications. A total of 425 individuals (1 eye/1 patient) were included. Reduced VD and FAZc were associated with greater categories of GFR (p = 0.002, p = 0.04), ACR (p = 0.003, p = 0.005) and KDIGO risk prognosis classifications (p = 0.002, p = 0.005). FAZc was significantly reduced in greater KDIGO prognosis risk categories (low risk vs. moderate risk, 0.65 ± 0.09 vs. 0.60 ± 0.07, p < 0.05). VD and FAZc presented the best diagnostic performance in ROCs. In conclusion, OCTA parameters, such as VD and FAZc, are able to detect different GFR, ACR, and KDIGO categories in T1DM patients and controls in a non-invasive, objective quantitative way. FAZc is able to discriminate within T1DM patients those with greater DKD categories and greater risk of DKD progression.

Uveitic macular edema response to intravitreal dexamethasone implant is independent of optical coherence tomography findings.

PURPOSE: To identify predictive response optical coherence tomography (OCT) findings in uveitic macular edema (UME) treated with intravitreal dexamethasone implant (DEX). METHODS: Retrospective study of 66 eyes (53 patients) treated with DEX for UME. SD-OCT macular scans were collected prior to DEX treatment and 6 weeks and 3 months after the DEX implant. OCT images were evaluated for qualitative and quantitative characteristics (central retinal thickness, CRT and macular volume, MV). A multivariate analysis of covariance (ANCOVA) was carried out to study the predictive influence of OCT and clinical covariates on outcomes. The main outcome was a composite endpoint based on the simultaneous gain of 5 or more letters associated with a 20% or more reduction in CRT. RESULTS: A significant improvement in BCVA at 6 weeks (mean change from baseline -0.2, SD 0.3) and 3 months (mean -0.2, SD 0.4) was observed after the DEX implant. A significant decrease in CRT (change from baseline -187.7 µm at 3 months) and MV (change from baseline -1.7 mm3 at 3 months) were also observed. An association of ≥ 5-letter improvement in BCVA and a ≥ 20% CRT reduction was observed in 44.6% of cases at 6 weeks and 31.4% at 3 months. ANCOVA multivariate analyses found CRT at 3 months independent from baseline clinical variables but from CRT. CONCLUSION: DEX implant is an effective treatment for UME independently of basal characteristics, producing both a gain of visual acuity and improvement of macular anatomy by OCT measures at 3 months.

Differential response to intravitreal dexamethasone implant in naïve and previously treated diabetic macular edema eyes.

BACKGROUND: To identify different response patterns to intravitreal dexamethasone implants (IDI) in naïve and previously treated (PT) diabetic macular edema (DME) eyes in a real-life setting. METHODS: 342 IDI injections (203 DME eyes) were included. Number of IDI injections, percentage (%) of eyes with 1, 2, 3 and ≥ 4 injections, time to reinjections, visual acuity (VA), intraocular pressure (IOP) and central retinal thickness (CRT) were evaluated for naïve and PT DME eyes over 24 months. RESULTS: Mean number of injections was significantly lower in naïve vs PT DME eyes (1.40 ± 0.9 vs 1.82 ± 0.9, p < 0.001). The percentage of eyes receiving 1 injection was significantly higher in naïve vs PT DME eyes (76.1 vs 47.7), (p < 0.001). However, it was significantly lower for 2 (16.4 vs 29.4), or 3 injections (1.4 vs 17.6) (both p < 0.001), with no differences in eyes receiving ≥4 injections (5.9 vs 5.1 respectively, p = 0.80). Mean time to reinjection was not significantly different between both groups for the second, third and fourth injection (9.6 ± 4.0 vs 10.0 ± 5.5, p = 0.75, 13.2 ± 4.0 vs 16.0 ± 3.5, p = 0.21 and 21.7 ± 3.8 vs 19.7 ± 5.8, p = 0.55). VA scores were consistently better in naïve vs PT DME eyes at all studied timepoints, with no significant differences in CRT reduction or adverse effect rates. CONCLUSION: Naïve DME eyes received lower number of IDI injections and showed better VA levels than PT DME eyes for 24 months in a real-world setting. This data supports the IDI use in early DME stages and provide further evidence of better IDI response when used as first-line therapy.

Early Detection of Incipient Retinal Pigment Epithelium Atrophy Overlying Drusen with Fundus Autofluorescence vs. Spectral Domain Optical Coherence Tomography.

PURPOSE: This study aims to find out which tool, fundus autofluorescence (FAF) or spectral domain optical coherence tomography (SD-OCT), is more sensitive in detecting retinal pigment epithelium (RPE) demise overlying drusen and can, therefore, help predict geographic atrophy (GA) appearance in Age-Related Macular Degeneration (AMD). METHODS: A single-site, retrospective, observational, longitudinal study was conducted. Patients with intermediate AMD (iAMD) (large (>125 µm) or intermediate (63-125 µm) drusen with hyper/hypopigmentation) with a minimum follow-up of 18 months were included. Drusen with overlying incipient RPE atrophy were identified on SD-OCT defined as choroidal hypertransmission or nascent geographic atrophy (nGA). These selected drusen were, then, traced backwards in time to determine if incipient RPE atrophy overlying drusen was observed on FAF (well-demarcated region of absence of autofluorescence) before, simultaneously, or after having detected the first signs of incipient RPE atrophy on SD-OCT. The number of drusen in which signs of incipient RPE atrophy was detected earlier using FAF or SD-OCT was compared. The time elapsed from the identification with the more sensitive method to the other was recorded and analyzed. RESULTS: One hundred and thirty-three drusen in 22 eyes of 22 patients were included. Of these, 112 (84.2%) drusen showed choroidal hypertransmission and 21(15.8%) nGA. Early signs of atrophy overlying drusen were found simultaneously on SD-OCT and FAF in 52 cases (39.1%, 95% CI 30.8-47.9%), earliest on FAF in 51 (38.3%, 95% CI 30.0-47.2%) and first on SD-OCT in 30 (22.6%, 95% CI 15.8-30.6%; p < 0.05). Statistically significant differences were found between both techniques (p=0.005), with FAF detecting it earlier than SD-OCT. When RPE atrophy was found first on FAF, the median time to diagnosis with SD-OCT was 6.6 months (95% CI 5.5 to 8.6), while if detection occurred earlier on SD-OCT, the median time until identification with FAF was 12.6 months (95% CI 6.0 to 23.4; p=0.0003). CONCLUSIONS: In iAMD cases in which early atrophy overlying drusen is not detected simultaneously in FAF and SD-OCT, FAF was significantly more sensitive. Nevertheless, a multimodal approach is recommended and required to evaluate these patients.

Optical Coherence Tomography Angiography in Type 1 Diabetes Mellitus. Report 1: Diabetic Retinopathy.

Purpose: The purpose of this study was to evaluate specifically in type 1 diabetes mellitus (DM) individuals the relationship between perifoveal superficial capillary plexus (SCP) parameters assessed by optical coherence tomography angiography (OCTA) and diabetic retinopathy (DR) grade. Methods: Cross-sectional analysis of a large scale prospective OCTA trial cohort (ClinicalTrials.gov NCT03422965). A total of 1186 eyes (593 individuals), 956 type 1 DM eyes (478 patients), and 230 control eyes (115 healthy volunteers) were included in this study. DR stage was graded according to the International Classification. OCTA imaging was performed with a commercially available device (Cirrus HD-OCT). Vessel density (VD), perfusion density (PD), and foveal avascular zone (FAZ) area, perimeter and circularity measurements were quantified in the SCP and receiver operating characteristic (ROC) curves were constructed for each OCTA parameter. Results: VD and PD (in both 3 × 3 and 6 × 6 mm captures) were inversely associated with DR stage (P < 0.001 in all cases) in a multiple regression analysis after controlling by age, gender, signal strength index, axial length, and DM duration. Greater FAZ area and perimeter and conversely lower circularity measurements were observed as DR severity increased in both scanning protocols (P < 0.05 in all cases). Conclusions: In type 1 DM individuals, OCTA provides an objective, continuous, and reliable method for accurate quantification of VD, PD, and FAZ parameters in the SCP, which ultimately correlate with DR stages. Translational Relevance: Objective OCTA measurements of the retinal microvasculature could substitute the clinical DR classification in patients with type 1 DM, identify patients at risk of DR progression, and inform treatment decisions to modify the evolution of the disease.

Baseline predictors for visual acuity loss during observation in diabetic macular oedema with good baseline visual acuity.

PURPOSE: To investigate clinical baseline characteristics and optical coherence tomography biomarkers predicting visual loss during observation in eyes with diabetic macular oedema (DMO) and good baseline visual acuity (VA). METHODS: A sub-analysis of a 12-month, retrospective study, including patients with baseline VA ≤0.1 logMAR (≥20/25 Snellen) and centre-involving DMO. The primary outcome measure was the correlation between baseline characteristics and VA loss ≥10 letters during follow-up. RESULTS: A total of 249 eyes were included in the initial study, of which 147 eyes were observed and 80 eyes received anti-vascular endothelial growth factor (VEGF) treatment at baseline. Visual acuity (VA) loss ≥10 letters occurred in 21.8% (observed cohort) and in 24.3% (treated cohort), respectively. Within observed eyes, presence of hyperreflective foci [HRF; odds ratio (OR): 3.18, p = 0.046], and disorganization of inner retina layers (DRIL; OR: 2.71, p = 0.026) were associated with a higher risk of VA loss ≥10 letters. In observed eyes with a combined presence of HRF, DRIL and ellipsoid zone (EZ) disruption, the risk of VA loss was further increased (OR: 3.86, p = 0.034). In eyes with combined presence of DRIL, HRF and EZ disruption, risk of VA loss was 46.7% (7/15 eyes) in the observed cohort, and 26.3% (5/19 eyes) in the treated cohort (p = 0.26). CONCLUSION: Patients with DMO and good baseline VA, managed by observation, are of increased risk for VA loss if DRIL, HRF and EZ disruption are present at baseline. Earlier treatment with anti-VEGF in these patients may potentially decrease the risk of VA loss at 12 months.

Long-Term Intravitreal Dexamethasone Implant Outcomes in Uveitis.

Purpose: To describe the long-term clinical outcomes in a cohort of uveitic eyes treated with the intravitreal dexamethasone implant (Ozurdex; Allergan, Inc).Methods: Seventy-nine (63 patients) receiving 134 implant injections over 82 months were included. Indication, visual acuity (VA), intraocular pressure (IOP), vitreous haze score (VHS), central retinal thickness (CRT), time to reinjection, systemic treatments, and complications data were recorded.Results: The cumulative probability of VA improvement was 80% at 1 month and 90% at 12 months, and it was maintained until 60 months. Eyes with baseline vitritis (VHS >0.5; 68%) had a probability of VHS improvement of 33% at 1 month, 75% at 12 months, and 85% at 60 months. The probability of CRT improvement was 33% at 1 month, 75% at 12 months, and 85% at 60 months. The most frequent adverse event was moderate IOP elevation (≥25 mmHg) in 30.3%, no cases of retinal detachment or endophthalmitis were observed.Conclusions: The dexamethasone implant provides favorable VA, CRT, and VHS long-term outcomes in uveitis with a reduced rate of severe adverse events.

Disorganization of retinal inner layers as a biomarker in patients with diabetic macular oedema treated with dexamethasone implant.

PURPOSE: To investigate disorganization of retinal inner layers (DRIL) as a biomarker in eyes with diabetic macular oedema (DME) treated by intravitreal dexamethasone (DEX) implant. METHODS: Multicentre, retrospective study including eyes with DME treated with DEX implant and follow-up of 12 months after the first injection. OCT scans were evaluated for the presence of DRIL and other structural features. Best corrected visual acuity (BCVA) and central subfield thickness (CST) were recorded at baseline and at 2, 4, 6 and 12 months after treatment. Correlation between DRIL at baseline and outcomes after DEX treatment and the change in DRIL were analysed. RESULTS: A total of 177 eyes (177 patients; naïve, n = 131; refractory, n = 46) were included. Patients without DRIL at baseline gained significantly more vision and enjoyed greater reduction in CST over 12 months (both p = 0.03). DRIL at the boundary between the ganglion cell-inner plexiform complex and inner nuclear layer improved in 48/64 eyes (75%, p < 0.001), while DRIL between the inner nuclear layer and outer plexiform layer improved in 27/77 eyes (35%, p = 0.004). CONCLUSIONS: This is the first study to show that DEX implant has the potential to ameliorate DRIL. Patients without DRIL at baseline have a favourable outcome. DRIL may serve a robust biomarker in DME treated by DEX implant.

Evaluation of microvascular changes in the perifoveal vascular network using optical coherence tomography angiography (OCTA) in type I diabetes mellitus: a large scale prospective trial.

BACKGROUND: Diabetic retinopathy (DR) is the leading cause of blindness in type 1 Diabetes Mellitus (DM) patients, as a consequence of impaired blood flow in the retina. Optical coherence tomography angiography (OCTA) is a newly developed, non-invasive, retinal imaging technique that permits adequate delineation of the perifoveal vascular network. It allows the detection of paramacular areas of capillary non perfusion and/or enlargement of the foveal avascular zone (FAZ), representing an excellent tool for assessment of DR. The relationship of these microvascular changes with systemic factors such as metabolic control or duration of the disease still needs to be elucidated. METHODS: Prospective, consecutive, large-scale OCTA study. A complete ocular examination including a comprehensive series of OCTA images of different scan sizes captured with 2 OCT devices (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA, USA, and Triton Deep Range Imaging OCT, Topcon Corp, Topcon, Japan) will be obtained as part of the yearly routine follow up visits in type 1 DM patients seen in the Diabetes Unit of the Endocrinology department which give written informed consent to participate in the project. The aim of this study is to investigate the relationship between OCTA-derived parameters and systemic factors, as metabolic control (Hb1Ac, lipid profile, cholesterol, etc), and other relevant clinical factors as demographics or duration of the disease. DISCUSSION: This study is directed to investigate the relationship between the status of the perifoveal vascular network and systemic markers of the disease, and in particular to study whether these changes reflect those occurring elsewhere in the body affected by diabetic microvascular disease, as the kidneys or the brain. If these relationships were demonstrated, early detection of these microvascular changes by OCTA could lead to modifications in the pharmacological management of type 1 diabetic patients, as a way to reduce the risk of future complications in both the eye and other organs. TRIAL REGISTRATION: ClinicalTrials.gov, trial number NCT03422965.

Multimodal retinal imaging of familial amyloid polyneuropathy.

Background: Retinal amyloid angiopathy is a sight-threatening complication of familial amyloid polyneuropathy (FAP) caused by pathological deposition of transthyretin. The purpose of this report is to present ocular findings in patients with FAP using a combination of novel non-invasive retinal imaging techniques, including first time published images of optical coherence tomography angiography (OCT-A) in FAP.Materials and methods: Observational cross-sectional study of retinal images in patients with FAP using: fundus ultra wide-field photography (UWF); autofluorescence (AF); optical coherence tomography (OCT); and, OCT-A. Fifteen eyes of eight patients with FAP from a tertiary center were included. A descriptive analysis of obtained images and clinical data was performed.Results: Amyloid vitreous and retinal deposits were easily identified using OCT scans, AF, and UWF images, especially in the red-free modality. OCT-A allowed quality reconstruction of posterior pole vasculature, foveal avascular zone, and areas of ischemia.Conclusions: Different modalities of currently available non-invasive retinal imaging techniques, including OCT-A scans described for the first time in FAP, are safe and useful in detecting and analyzing retinal amyloidosis. Retinopathy in FAP in the studied group was more frequent than previously reported.

Aqueous Humour Cytokine Changes with Intravitreal Dexamethasone Implant Injection for Diabetic Macular Edema.

Purpose: To assess changes in aqueous humor (AH) levels of cytokines following dexamethasone intravitreal implant (DEX) injection for diabetic macular edema (DME).Methods: Sixteen DME and cataract cases series study. Anterior chamber AH sampling was performed at baseline at DEX injection time (T1), cataract surgery 8 weeks afterward (T2), and whenever DME relapsed (T3) in order to assess changes in IL-1ß, IL-3, IL-6, IL-8, IL-10, MCP-1, IP-10, TNF-α, and VEGF levels.Results: IP-10 and MCP-1 levels significantly decreased at T2 (p = .034 and p = .044, respectively) compared to baseline (T1). Relapsed DME cases (T3) showed significantly higher levels of IL-6 (p = .028), IL-8 (p = .005), IP-10 (p = .013) and MCP-1 (p = .005) compared to T2.Conclusion: IP-10 and MCP-1 AH levels seem to be related to DEX intraocular action, decreasing after injection and increasing when DME relapses. In addition, IL-6 and IL-8 may play a role in DME late evolution and clinical relapse beyond DEX effect.

Anatomic Response to Intravitreal Dexamethasone Implant and Baseline Aqueous Humor Cytokine Levels in Diabetic Macular Edema.

Purpose: To determine whether baseline cytokine aqueous humor (AH) levels are associated with diabetic macular edema (DME) anatomic response to dexamethasone intravitreal implant (DEX) injection. Methods: This was a prospective cohort study of DME cases receiving DEX treatment. Seventy patients were recruited with center-involving DME with spectral-domain (SD) optical coherence tomography (OCT) detection of central macular thickness (CMT) ≥300 µm on macular cube 518 × 128-µm scan protocol (Cirrus SD-OCT). DEX injection and anterior chamber tap to obtain an AH sample were performed at the same time. Multiplex immunoassay was carried out for interleukin (IL)-1ß, IL-3, IL-6, IL-8, IL-10; monocyte chemoattractant protein (MCP)-1; interferon gamma-induced protein (IP)-10; tumor necrosis factor (TNF)-α; and vascular endothelial growth factor (VEGF). A follow-up visit and OCT exam were undertaken 6 to 8 weeks afterward. The association between AH cytokine baseline levels and change in CMT and macular volume (MV) was defined as main outcome measure. Results: Multivariate linear regression analysis showed a higher decrease in MV to be associated (Rs of 0.512) with four baseline items: higher MCP-1 (ß = -0.4; P = 0.028), higher CMT (ß = -0.003; P = 0.024), decreased visual acuity (ß = -0.7; P = 0.040), and a diffuse retinal thickening (DRT) OCT pattern (ß = -1.3; P < 0.001). Logistic regression found DRT also to be associated with higher odds of a good MV response (odds ratio, 31.96; 95% confidence interval [CI] 7.11-143.72; P < 0.001). Conclusions: Even though visual acuity response and anatomic effect are not always correlated in DME, we found that baseline elevated MCP-1 AH levels and DRT pattern were biomarkers that predicted a future favorable anatomic response to DEX.

Real-world outcomes of observation and treatment in diabetic macular edema with very good visual acuity: the OBTAIN study.

AIMS: To describe and compare the functional and anatomical outcomes of untreated and treated diabetic macular edema (DME) in eyes with very good baseline visual acuity (VA) in a real-world setting. METHODS: A 12-month, retrospective, multicenter, observational cohort study, including DME patients with baseline visual acuity (VA) ≤ 0.1 logMAR (≥ 20/25 Snellen) and central subfield thickness (CST) > 250 µm with intra- and/or subretinal fluid seen on optical coherence tomography. RESULTS: A total of 249 eyes were included, of which 155 were treated and 94 were non-treated during follow-up. Most eyes maintained vision (VA gain or VA loss < 5 letters) at 12 months (treated: 58.1%; non-treated: 73.4%). In non-treated eyes with stable VA within the first 6 months, VA was maintained throughout the follow-up in most cases (86.3%). In non-treated eyes with VA loss ≥ 5 letters within 6 months (36.7%), further observation led to worse visual outcome than treatment (- 4.2 vs. - 7.8 letters, p = 0.013). In eyes in which treatment was initiated at baseline (n = 102), treatment with 8-12 anti-VEGF injections led to better visual outcome compared to treatment with less injections (- 0.3 ± 3.6 letters vs. - 3.8 ± 6.2 letters, p = 0.003). CONCLUSION: In a real-world setting, the majority of DME patients with very good VA maintained vision at 12 months, regardless of whether the DME was treated or not. This study supports close observation of eyes with DME and very good VA with consideration of treatment when a one line drop in vision is observed.

Causative Pathogens of Endophthalmitis after Intravitreal Anti-VEGF Injection: An International Multicenter Study.

PURPOSE: The main objective of this study was to investigate the microbiological spectrum of endophthalmitis after anti-VEGF injections and to compare streptococcal with non-streptococcus-associated cases with regard to baseline characteristics and injection procedure. METHODS: Retrospective, international multicenter study of patients with culture-positive endophthalmitis after intravitreal anti-VEGF injection at 17 different retina referral centers. RESULTS: Eighty-three cases with 87 identified pathogens were included. Coagulase-negative staphylococci (59%) and viridans streptococci (15%) were the most frequent pathogens found. The use of postoperative antibiotics and performance of injections in an operating room setting significantly reduced the rate of streptococcus-induced endophthalmitis cases (p = 0.01 for both). CONCLUSION: We found a statistically significant lower rate of postinjectional local antibiotic therapy and operating room-based procedures among the streptococcus-induced cases compared to cases caused by other organisms.