To evaluate the effects of repeated intravitreal dexamethasone implant.
We reviewed the charts of 12 patients with diabetic macular edema, who received at least 2 intravitreal Ozurdex (0.7 mg) on an ..."as needed" basis. Main outcome measures included changes in best-corrected visual acuity, central macular thickness, retreatment interval, and incidence of side effects.
A total of 15 eyes of 12 patients (6 men, 6 women; mean age 62 ± 12 years) were included. Retreatment was judged necessary after mean of 7.8 ± 4.1 months from the first Ozurdex (median, 6 months) (15 of 15 eyes), mean of 4.8 ± 0.9 months from the second Ozurdex (median, 5 months) (7 of 15 eyes), mean of 5.3 ± 1.5 months from the third Ozurdex (median, 5 months) (3 of 15 eyes), and mean of 5.6 ± 2 months from the fourth Ozurdex (median, 5 months) (3 of 15 eyes). Mean baseline best-corrected visual acuity was 0.67 ± 0.33 logMAR in the overall diabetic macular edema population; it significantly improved to 0.53 ± 0.31 logMAR after mean of 40.9 ± 18.2 days from the first Ozurdex (peaking efficacy) (P < 0.001), to 0.53 ± 0.29 logMAR after mean of 34.4 ± 9.0 days from the second Ozurdex (peaking efficacy) (P < 0.003), and stabilized to 0.62 ± 0.26 logMAR after mean of 29.8 ± 12.1 days from the third Ozurdex (peaking efficacy) (P = 0.05), to 0.5 ± 0.26 logMAR after mean of 36.3 ± 3.2 days from the fourth Ozurdex (peaking efficacy) (P = 0.2), and to 0.50 ± 0.26 logMAR after mean of 37.0 ± 2.6 days from the fifth Ozurdex (peaking efficacy) (P = 0.2). Mean baseline central macular thickness significantly decreased from 546 ± 139 μm to 292 ± 43 μm at 39.4 ± 17.9 days from the first Ozurdex (peaking efficacy) (P < 0.001), to 297 ± 47 μm at 33 ± 9.4 days from the second Ozurdex (peaking efficacy) (P < 0.001), to 293 ± 22 μm at 29.8 ± 12.1 days from the third Ozurdex (peaking efficacy) (P = 0.01), and stabilized to 309 ± 35 μm at 36.3 ± 3.2 days from the fourth Ozurdex (peaking efficacy) (P = 0.1), and to 295 ± 7 μm at 37.0 ± 2.6 days from the fifth Ozurdex (peaking efficacy) (P = 0.1). No serious adverse events were observed; three eyes developed a transient intraocular pressure increase, and cataract was extracted in one eye.
Repeated intravitreal Ozurdex on an "as needed" basis with a variable retreatment interval may produce long-term clinically meaningful benefits in the treatment of diabetic macular edema, without other significant side effects than expected after intraocular corticosteroid treatment.
This cross-sectional study evaluated the relationship between
) functional and structural measurements of neurodegeneration in the initial stages of diabetic retinopathy (DR) and
) the presence of ...neurodegeneration and early microvascular impairment. We analyzed baseline data of 449 patients with type 2 diabetes enrolled in the European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR) study (NCT01726075). Functional studies by multifocal electroretinography (mfERG) evaluated neurodysfunction, and structural measurements using spectral domain optical coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1 implicit time and was lower in patients with Early Treatment of Diabetic Retinopathy Study (ETDRS) level 20-35 than in patients with ETDRS level <20 (
= 0.005). In 58% of patients, mfERG abnormalities were present in the absence of visible retinopathy. Correspondence between SD-OCT thinning and mfERG abnormalities was shown in 67% of the eyes with ETDRS <20 and in 83% of the eyes with ETDRS level 20-35. Notably, 32% of patients with ETDRS 20-35 presented no abnormalities in mfERG or SD-OCT. We conclude that there is a link between mfERG and SD-OCT measurements that increases with the presence of microvascular impairment. However, a significant proportion of patients in our particular study population (ETDRS ≤35) had normal ganglion cell-inner plexiform layer thickness and normal mfERG findings. We raise the hypothesis that neurodegeneration may play a role in the pathogenesis of DR in many but not in all patients with type 2 diabetes.
Purpose
This is a retrospective real‐world study on the use of Fluocinolone acetonide (FAc) intravitreal implant (Iluvien®) for the treatment of chronic diabetic macular edema (DME) insufficiently ...responsive to available therapies. Its aim is to give a further contribution in assessment of efficacy and safety of this drug delivery system.
Methods
Patients included were collected from July 2017 to May 2019. 53 pseudophakic chronic DME patients (69 eyes) were enrolled to evaluate anatomo‐functional outcomes; namely, best corrected visual acuity (BCVA), central macular thickness (CMT) and complications (i.e. rise in intraocular pressure (IOP) and need for IOP lowering medications, hemovitreous, endophtalmitis) of Iluvien® implants. The study partecipants were all previously unsuccessfully treated with first‐line therapies (anti‐VEGF and laser) and intravitreal dexamethasone (Ozurdex®). Patients were considered eligible only in presence of response to the latter drug without significant intra‐ocular pressure increase. Information about further need for DME additional therapies post‐FAc were also recorded. The data of 18 eyes with at least 12 months follow‐up are reported.
Results
At baseline the mean overall BCVA was 58.3±17.5 ETDRS scale letters. Post‐FAc implant, mean BCVA rised to 63.9 ± 15.2, 60.8 ± 18.3, 61.3 ± 16.9 and 64.5 ± 13.9 ETDRS letters at 2, 4, 6 and 12 months respectively. The percentage of eyes achieving 15 or more ETDRS letters improvement within 12 months was 33.3%. CMT values, from a baseline mean of 517.4 ± 204.0 µm, decreased to 364.9 ± 138.4 µm, 410.8 ± 192.4 µm, 339.0 ± 126.8 µm and 339.9 ± 82.0 at 2, 4, 6 and 12 months, respectively. In this period of observation a dry macula (<300 µm) was obtained in 33.3% of eyes. Recorded complications included increase in IOP with need for IOP lowering medications in 18.9% of study population. Only 8.7% patients needed to perform additional DME therapies for poor response to FAc.
Conclusions
The preliminary results of our study support the use of FAc for the treatment of chronic DME. Efficacy and safety profiles seem to be comparable with the ones of the FAME pivotal study but with less IOP concerns. Selecting patients previously treated with intravitreal steroids and without increase in IOP can further minimize risks. Mean increase of IOP over time can be safely managed with topical therapy in the large majority of cases.
The aim of our study was to investigate factors associated with diabetic retinopathy (DR) severity fluctuations in patients undergoing intravitreal injections for diabetic macular edema and to ...explore risk factors for proliferative DR (PDR).
We graded ultra-widefield fundus photography imaging at each visit using the Early Treatment Diabetic Retinopathy Study Severity Scale (DRSS). We calculated the deviation from the mode (DM) of DRSS values as a proxy of DR severity fluctuations, and we analyzed its clinical associations with linear models. We computed risk factors for PDR with Cox hazard models. We included the DRSS area-under-the-curve (AUC) of DRSS scores as a covariate in all analyses.
We included 111 eyes with a median follow-up of 44 months. Higher DRSS-AUC values (β = +0.03 DRSS DM for unitary DRSS/month increase, p = 0.01) and a higher number of anti-VEGF injections (β = +0.07 DRSS DM for injection, p = 0.045) were associated with wider DR severity fluctuations. Higher DRSS-AUC values (HR = 1.45 for unitary DRSS/month increase, p = 0.001) and wider DR severity fluctuations (HR = 22.35 4th quartile vs. 1st-3rd quartile of DRSS DM, p = 0.01) were risk factors for PDR.
Patients with larger DR variability in response to intravitreal injections may be at higher risk of DR progression. We advocate attentive follow-up in these patients to recognize PDR early.
The study retraces the healthcare pathway of patients affected by diabetic macular edema (DME) through the direct voice of patients and caregivers by using a “patient journey” and narrative method ...approach. The mapping of the patient’s journey was developed by a multidisciplinary board of health professionals and involved four Italian retina centers. DME patients on intravitreal injection therapy and caregivers were interviewed according to the narrative medicine approach. Narratives were analyzed through a quali-quantitative tool, as set by the narrative medicine method. The study involved four specialized retina centers in Italy and collected a total of 106 narratives, 82 from DME patients and 24 from caregivers. The narratives reported their difficulty in identifying the correct pathway of care because of a limited awareness of diabetes and its complications. Patients experienced reduced autonomy due to ocular complications. In the treatment of diabetes and its complications, a multidisciplinary approach currently appears to be missing. DME reduces the quality of life of affected patients. The narrative medicine approach offers qualitative and emotional patient-guided information. The patient journey provides all of those involved in the management of DME with flowcharts to refer to, identifying the critical points in the healthcare journey of DME patients to improve the management of the disease.
Retinal vein occlusion is the second most common retinal vascular pathology after diabetic retinopathy and a major cause of vision impairment. Nowadays, both central retinal vein occlusion (CRVO) and ...branch retinal vein occlusion (BRVO) can be well-managed by intravitreal treatments. However, considering the long-life expectance of the patients, few data are present in the literature about the very long-term outcome of CRVO and BRVO. The present study was an interventional, retrospective analysis of the morphological and functional long-term outcome of CRVO and BRVO patients, followed in an Italian referral center. We collected data from 313 eyes (178 CRVO eyes and 135 BRVO eyes). Mean follow-up was 45 ± 25 months (range 12-84 months). Both CRVO and BRVO eyes experience a significant visual acuity improvement secondary to anti-vascular endothelial growth factor/dexamethasone treatments (from 0.57 ± 0.25 to 0.41 ± 0.24 LogMAR in CRVO and from 0.53 ± 0.42 to 0.30 ± 0.41 LogMAR in BRVO, respectively) (
< 0.01). Also, central macular thickness (CMT) resulted significant recovery at the end of the follow-up (from 585.54 ± 131.43 to 447.88 ± 245.07 μm in CRVO and from 585.54 ± 131.43 to 447.88 ± 245.07 μm in BRVO, respectively) (
< 0.01). CRVO eyes received a mean of 10.70 ± 4.76 intravitreal treatments, whereas BRVO underwent 9.80 ± 5.39 injections over the entire 7-year follow-up. Our analyses highlighted different time points indicating the best obtainable improvement. This was the first year for CRVO (12-month follow-up) and the second year for BRVO (24-month follow-up). After these two time points, both visual acuity and CMT resulted stable up to the end of the follow-up. Ischemia was associated with significantly worse outcome.
To compare the diagnostic performance of artificial intelligence (AI)-based diabetic retinopathy (DR) staging system across pseudocolor, simulated white light (SWL), and light-emitting diode (LED) ...camera imaging modalities.
A cross-sectional investigation involved patients with diabetes undergoing imaging with an iCare DRSplus confocal LED camera and an Optos confocal, ultra-widefield pseudocolor camera, with and without SWL. Macula-centered and optic nerve-centered 45 × 45-degree photographs were processed using EyeArt v2.1. Human graders established the ground truth (GT) for DR severity on dilated fundus exams. Sensitivity and weighted Cohen's weighted kappa (wκ) were calculated. An ordinal generalized linear mixed model identified factors influencing accurate DR staging.
The study included 362 eyes from 189 patients. The LED camera excelled in identifying sight-threatening DR stages (sensitivity = 0.83, specificity = 0.95 for proliferative DR) and had the highest agreement with the GT (wκ = 0.71). The addition of SWL to pseudocolor imaging resulted in decreased performance (sensitivity = 0.33, specificity = 0.98 for proliferative DR; wκ = 0.55). Peripheral lesions reduced the likelihood of being staged in the same or higher DR category by 80% (P < 0.001).
Pseudocolor and LED cameras, although proficient, demonstrated non-interchangeable performance, with the LED camera exhibiting superior accuracy in identifying advanced DR stages. These findings underscore the importance of implementing AI systems trained for ultra-widefield imaging, considering the impact of peripheral lesions on correct DR staging.
This study underscores the need for artificial intelligence-based systems specifically trained for ultra-widefield imaging in diabetic retinopathy assessment.
Purpose To evaluate intravitreal aflibercept for treatment of macular edema secondary to central retinal vein occlusion (CRVO). Design Randomized, double-masked, phase 3 study. Methods A total of 177 ...patients with macular edema secondary to CRVO were randomized to receive 2 mg intravitreal aflibercept (n = 106) or sham (n = 71) every 4 weeks for 20 weeks. From weeks 24 to 48, patients were monitored every 4 weeks; the former group received intravitreal aflibercept as needed (PRN), and the sham group received sham. From weeks 52 to 76, patients were monitored every 8 weeks, and both groups received intravitreal aflibercept PRN. The primary endpoint (proportion of patients who gained ≥15 letters) was at week 24. This study reports exploratory outcomes at week 76. Results The proportion of patients who gained ≥15 letters in the intravitreal aflibercept and sham groups was 60.2% vs 22.1% at week 24 (patients discontinued before week 24 were considered nonresponders; P < .0001), 60.2% vs 32.4% at week 52 (last observation carried forward, P < .001), and 57.3% vs 29.4% at week 76 (last observation carried forward; P < .001). Mean μm change from baseline central retinal thickness was −448.6 vs −169.3 at week 24 ( P < .0001), −423.5 vs −219.3 at week 52 ( P < .0001), and −389.4 vs −306.4 at week 76 ( P = .1122). Over 76 weeks, the most common ocular serious adverse event in the intravitreal aflibercept group was macular edema (3.8%). Conclusions The visual and anatomic improvements seen after fixed, monthly dosing at week 24 were largely maintained when treatment intervals were extended. Patients with macular edema following CRVO benefited from early treatment with intravitreal aflibercept.
To evaluate the effects of repeated intravitreal dexamethasone implant (IDI) (Ozurdex®) in eyes with macular edema (ME) due to retinal vein occlusion (RVO).
We reviewed the charts of patients with ...RVO-related ME, who received repeated Ozurdex IDI (0.7 mg) on an 'as-needed' basis. Main outcome measures included changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), retreatment interval, and incidence of side effects.
A total of 33 eyes were included for analysis. Retreatment with Ozurdex was judged necessary after 4.7 ± 1.1 months from the first IDI (1st IDI) and 5.1 ± 1.5 months from the second IDI (2nd IDI). Baseline BCVA was 0.65 ± 0.43 logMAR; it significantly improved to 0.50 ± 0.42 logMAR after 1.4 ± 0.7 months from the 1st IDI (peaking efficacy) (p < 0.001) and to 0.48 ± 0.44 logMAR after 1.8 ± 0.8 months from the 2nd IDI (peaking efficacy) (p < 0.001). CMT decreased from 636 ± 217 µm (baseline) to 300 ± 114 µm, 1.4 ± 0.7 months after the 1st IDI (p < 0.001), and to 298 ± 91 µm, 1.8 ± 0.8 months after the 2nd IDI (p < 0.001). A rebound effect was recorded in 7 eyes after the 1st IDI (mean 168 ± 158 µm) and in 4 eyes after the 2nd IDI (mean 215 ± 199 µm). All eyes with a rebound effect improved again after a 2nd intravitreal Ozurdex injection. No serious adverse events were observed; 12 eyes developed a transient IOP increase, and cataracts were extracted in 2 eyes.
Repeated intravitreal Ozurdex on an 'as-needed' basis, with a retreatment interval <6 months, may produce long-term clinically meaningful benefits in the treatment of ME due to RVO, without other significant side effects than expected after intraocular corticosteroid treatment.
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