Intravitreal Therapy Research Articles

Fungal Infection After Descemet Membrane Endothelial Keratoplasty: Incidence and Outcomes.

The aim of the study was to describe the incidence, presentation, management, and outcomes of fungal infection after Descemet membrane endothelial keratoplasty (DMEK). Retrospective case series of culture-proven fungal infections after DMEK reported in the literature, directly by surgeons, and to the Eye Bank Association of America from January 1, 2011, to December 31, 2020. The domestic incidence of fungal infections, fungal keratitis, and fungal endophthalmitis after DMEK from 2011 to 2020 was 3.5, 1.3, and 2.2 per 10,000 cases, respectively, with no significant increasing trend. Thirty-four cases were identified, 14 (41.2%) published and 20 (58.8%) unpublished. Donor tissue fungal cultures were performed in 20 of the 34 (58.8%) cases and were positive in 19 of the 20 (95.0%), all but one Candida species. Recipient fungal cultures were performed in 29 of the 34 (85.3%) cases and were positive in 26 of the 29 (89.7%), all but one Candida species. Infection presented a mean of 33 ± 38 days (median 23, range 2-200, outlier 949) after transplantation: 25 (73.5%) with endophthalmitis and 9 (26.5%) with keratitis. Topical, intrastromal, intracameral, intravitreal, or systemic antifungal therapy was used in all 27 eyes with treatment data. Surgical intervention (DMEK explantation or partial removal, repeat endothelial keratoplasty, penetrating keratoplasty, and/or pars plana vitrectomy) was required in 21 of the 27 (77.8%) eyes. The corrected distance visual acuity at the last follow-up was ≥20/40 in 13 of the 27 (48.1%) eyes and counting fingers or worse in 6 of the 27 (22.2%) eyes. Fungal infection is a rare but serious complication of DMEK that results in counting fingers or worse corrected distance visual acuity in nearly a quarter of eyes.

Diabetic Macular Edema and Diode Subthreshold Micropulse Laser: A Randomized Double-Masked Noninferiority Clinical Trial

To determine clinical effectiveness, safety, and cost-effectiveness of subthreshold micropulse laser (SML), compared with standard laser (SL), for diabetic macular edema (DME) with central retinal thickness (CRT) < 400 μm. Pragmatic, multicenter, allocation-concealed, double-masked, randomized, noninferiority trial. Adults with center-involved DME < 400 μm and best-corrected visual acuity (BCVA) of > 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in one/both eyes. Randomization 1:1 to 577 nm SML or SL treatment. Retreatments were allowed. Rescue with intravitreal anti-vascular endothelial growth factor therapies or steroids was permitted if 10 or more ETDRS letter loss occurred, CRT increased > 400 μm, or both. Primary outcome was mean change in BCVA in the study eye at 24 months (noninferiority margin 5 ETDRS letters). Secondary outcomes were mean change from baseline to month 24 in binocular BCVA; CRT and mean deviation of Humphrey 10-2 visual field in the study eye; percentage meeting driving standards; EuroQoL EQ-5D-5L, 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), and Vision and Quality of Life Index (VisQoL) scores; cost per quality-adjusted life-years (QALYs) gained; adverse effects; and number of laser and rescue treatments. The study recruited fully (n= 266); 87% of SML-treated and 86% of SL-treated patients had primary outcome data. Mean ± standard deviation BCVA change from baseline to month 24 was -2.43 ± 8.20 letters and -0.45 ± 6.72 letters in the SML and SL groups, respectively. Subthreshold micropulse laser therapy was deemed not only noninferior but also equivalent to SL therapy because the 95% confidence interval (CI; -3.9 to -0.04 letters) lay wholly within both upper and lower margins of the permitted maximum difference (5 ETDRS letters). No statistically significant difference was found in binocular BCVA (0.32 ETDRS letters; 95% CI, -0.99 to 1.64 ETDRS letters; P= 0.63); CRT (-0.64 μm; 95% CI, -14.25 to 12.98 μm; P= 0.93); mean deviation of the visual field (0.39 decibels (dB); 95% CI, -0.23 to 1.02 dB; P= 0.21); meeting driving standards (percentage point difference, 1.6%; 95% CI, -25.3% to 28.5%; P= 0.91); adverse effects (risk ratio, 0.28; 95% CI, 0.06-1.34; P= 0.11); rescue treatments (percentage point difference, -2.8%; 95% CI, -13.1% to 7.5%; P= 0.59); or EQ-5D, NEI-VFQ-25, or VisQoL scores. Number of laser treatments was higher in the SML group (0.48; 95% CI, 0.18-0.79; P= 0.002). Base-case analysis indicated no differences in costs or QALYs. Subthreshold micropulse laser therapy was equivalent to SL therapy, requiring slightly higher laser treatments.

The Impact of the COVID-19 Pandemic on the Quality of Care of Treatment-Naïve Patients with Neovascular Age-Related Macular Degeneration Receiving Intravitreal Aflibercept.

The aim of this study was to compare the quality of care received by treatment-naïve patients with neovascular age-related macular degeneration (nAMD) who received intravitreal aflibercept therapy before the coronavirus disease 2019 (COVID-19) pandemic with patients who received the same therapy during the pandemic. Data, including best corrected visual acuity (BCVA) as the logarithm of the minimum angle of resolution (logMAR) and anatomical outcomes at diagnosis and at each follow-up, was collected on 297 treatment-naïve patients who received intravitreal aflibercept. Therapy-naïve patients who started therapy at least 24 months prior to the first pandemic-related lockdown and were thus treated exclusively prior to the pandemic (n = 123) were compared with patients who started therapy within 12 months prior to the first lockdown and were thus treated during the pandemic (n = 174). Both groups were followed over a two-year period. In patients treated before the COVID-19 pandemic, VA remained stable (0.58 ± 0.41 logMAR) compared to baseline (0.54 ± 0.34 logMAR; p = 0.228) until the end of the observation period. In patients treated during the COVID-19 pandemic, BCVA dropped below the baseline (0.56 ± 0.35 logMAR) within 24-month of follow-up (0.79 ± 0.43 logMAR; p = 0.010). Compared to the patients treated prior to the COVID-19 pandemic, the latter group showed a significantly worse VA at the 6-month (p = 0.041), 12-month (p = 0.040), 18-month (p = 0.024), 21-month (p = 0.035), and 24-month (p = 0.004) follow-up. Additionally, the group treated during the COVID-19 pandemic received significantly fewer aflibercept injections (3,94 ± 1,9 vs. 3,30 ± 1,6; p = 0,007) and fewer follow-up examinations (2,71 ± 1,2 vs. 2,16 ± 0,9; p < 0,001) in the second year compared to the group that was treated before the COVID-19 pandemic. We confirmed significantly worse VA outcomes in the group of nAMD patients treated during the COVID-19 pandemic. Impeded access to care could be attributed to the restrictions imposed owing to the COVID-19 pandemic.

The Narrative Medicine Approach in the Treatment of Diabetic Macular Edema: An Italian Experience

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.

Visual Functions Affecting Vision-Related Quality of Life Following Intravitreal Ranibizumab Therapy for Central Retinal Vein Occlusion.

Visual functions that affect vision-related quality of life (VR-QoL) before and after intravitreal injection of ranibizumab in patients with cystoid macular edema secondary to central retinal vein occlusion (CRVO-CME) are poorly understood. This multicenter, open-label, single-arm prospective study included 23 treatment-naïve patients with CRVO-CME. The best-corrected visual acuity (BCVA), letter contrast sensitivity (LCS), severity of metamorphopsia (M-CHARTS), amount of aniseikonia (New Aniseikonia Test), and stereopsis (Titmus Stereo Test and TNO stereotest) were examined every month from before treatment to 12 months after treatment. For VR-QoL assessment, the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was provided to the patients before treatment and at 3, 6, and 12 months after treatment. Stepwise multiple regression analysis revealed that the BCVA of the fellow eye was related to the VFQ-25 composite score before treatment, and that the BCVA of the fellow eye and TNO values were related to the VFQ-25 composite score 12 months after treatment. Changes in LCS were significantly correlated with changes in the VFQ-25 composite score. In patients with CRVO-CME, visual acuity of the fellow eye had the strongest impact on VR-QoL. The contrast sensitivity of the affected eye and stereopsis were also associated with VR-QoL.

Recurrent, bilateral endogenous Candida endophthalmitis with multiple focal chorioretinal lesions: management with pars plana vitrectomy and focal endolaser

PurposeBilateral endogenous Candida endophthalmitis (ECE) treatment usually involves administering systemic and intravitreal antifungal medications. In advanced cases with vitreous seeding, pars plana vitrectomy (PPV) is considered. The use of focal endolaser treatment to chorioretinal lesions has not been reported. We present a case of bilateral recurrent ECE treated with PPV and endolaser to elevated focal lesions.CaseA 45-year-old diabetic male presented with decreased visual acuity in both eyes (20/50 right eye, 20/150 left eye) and was found to have bilateral ECE with moderate vitritis and chorioretinal lesions. The initial treatment consisted of multiple intravitreal voriconazole injections to both eyes as well as systemic antifungal therapy. Resolution of ECE occurred after three months, but one year later despite therapy recurred bilaterally. Patient underwent PPV with endolaser to the elevated chorioretinal lesions in both eyes. One year later, his vision improved to 20/40 in both eyes, focal lesions were flat and resolved along with the ECE.ConclusionAdvanced or recurrent ECE that is refractive to intravitreal antifungal therapy may be treated with PPV. Endolaser therapy to the chorioretinal lesions is an additional local option that can resolve the activity of ECE.

Ocular inflammation after agitation of siliconized and silicone oil-free syringes: a randomized, double-blind, controlled clinical trial

BackgroundNoninfectious endophthalmitis may be misdiagnosed, leading to serious clinical implications. So far, its causative factors remain unknown. Therefore, this study assessed the role of silicone oil and syringe agitation in the development of inflammation after intravitreal injection of aflibercept.MethodsA randomized, double-blind, controlled clinical trial included subjects with an indication of intravitreal antiangiogenic therapy prior to vitrectomy for proliferative diabetic retinopathy. Aflibercept was injected 48 h before surgery. The control group received the injection without agitation, while the intervention group was injected with a previously agitated syringe by flicking with either a siliconized or silicone oil-free syringe. The primary endpoint was the presence of anterior chamber reaction (ACR) at 48 h. Aqueous samples were collected and underwent cytometric bead array analysis for quantification of interleukins and chemokines.ResultsForty-one individuals were included (21 in the agitation group and 20 in the no-agitation group). None of the included eyes showed baseline signs of AC cells, hyperemia or pain complaint, while 10% of control group and 80% of agitation group showed AC cells 48 h after injection of aflibercept with SR syringe. There were no differences in the mean variations of all cytokines and chemokines by agitation status. However, there was a marginally significant increase between the mean variations of IP-10 (p = 0.057) and IL-8 (p = 0.058) in the siliconized one.ConclusionThis clinical trial discloses a potential role of agitation and siliconized syringes in the development of inflammation after an intravitreal injection of aflibercept. These findings have important clinical implications for all healthcare practitioners who perform intravitreal injections.Trial Registration: Brazilian Registry of Clinical Trials, RBR-95ddhp. Registered 12 May 2019, http://www.ensaiosclinicos.gov.br/rg/RBR-95ddhp/

Intravitreal 5-Fluorouracil and Heparin to Prevent Proliferative Vitreoretinopathy: Results from a Randomized Clinical Trial

Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD. Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis. Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry. Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy. Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon. A total of 325 patients in 13 German trial sites had been randomized (verum, n= 163; placebo, n=162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P=0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P= 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified. Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD.

Safety and Outcomes of Intravitreal Aflibercept in Diabetic Macular Edema - A Systematic Review.

Recent evidence on the role of vascular endothelial growth factor (VEGF) in the pathogenesis of ischemia and microvascular hyperpermeability leading to macular edema has brought anti-VEGF intravitreal therapy into the limelight. We performed a systematic literature review focusing on the outcomes and safety of the intravitreal use of aflibercept in diabetic macular edema. The studies documented cases with at least three consecutive intravitreal injections of aflibercept (IVA) repeated monthly with a follow-up period of at least one year. The outcomes were evaluated in terms of reported functional and anatomical improvement of the macula, as reflected by changes in visual acuity and macular thickness measured by Optical Coherence Tomography (OCT). In addition, for safety assessment, all reported local and general adverse effects were analyzed. All studies showed an overall significant anatomical and functional improvement. In patients with the 5 IVA monthly at the beginning of the therapy, the visual gain at 52 weeks varied widely between 5 and 18.9 EDRS letters, with a mean value of 9.48 letters. The higher gain was obtained in treatment naïve patients, with worse VA and increased CST at baseline. The lower gain was obtained in patients previously treated with anti- VEGF. Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events were not statistically different between the aflibercept group and the laser group. Intravitreal aflibercept therapy provides significant improvement in visual acuity and a good safety profile. Randomized studies are needed to document the optimal frequency of intravitreal injections for optimal treatment.

ELEVATED LEVEL OF URIC ACID, BUT NOT GLUCOSE, IN AQUEOUS HUMOR AS A RISK FACTOR FOR DIABETIC MACULAR EDEMA IN PATIENTS WITH TYPE 2 DIABETES.

To determine the association of uric acid (UA) and glucose in aqueous humor with diabetic macular edema (DME) in patients with Type 2 diabetes. Patients with DME or diabetes mellitus without retinopathy were enrolled from August 2016 to December 2020. Nondiabetic patients with age-related cataract or age-related macular degeneration were included as controls. A total of 585 eyes from 585 patients were included for this study. Statistical analysis showed that aqueous UA was associated with central retinal thickness (r = 0.39, P < 0.0001), with higher levels of UA in severe DME and lower levels in mild DME, suggesting an ocular source of UA from the diabetic retina. Aqueous UA {odds ratio (OR), 6.88 (95% confidence interval [CI], 2.61-18.12)}, but not aqueous glucose (0.95 [95% CI, 0.73-1.23]) or serum UA (0.90 [95% CI, 0.66-1.23]), was a stronger predictor for DME than the duration of DM (1.26 [95% CI, 1.12-1.42]) or hemoglobin A1c (1.35 [95% CI, 0.99-1.83]). If aqueous UA (<2.46 mg/dL) and aqueous glucose (<6.43 mmol/L) were used as reference, high UA (≥2.46 mg/dL) alone was associated with 5.83-fold increase in risk of DME, but high glucose (≥6.43 mg/dL) alone was not associated with DME. Increased aqueous UA, but not glucose, is an independent risk factor for DME. These data suggest that an intravitreal UA-lowering therapy could be beneficial for DME.

Efficacy evaluation of intravitreal ranibizumab therapy for three types of retinopathy of prematurity

To evaluate efficacy of intravitreal ranibizumab (IVR) therapy for aggressive posterior retinopathy of prematurity (ROP), threshold ROP disease and type 1 pre-threshold ROP. A retrospective analysis was performed on 40 patients (76 eyes) who had IVR as the primary treatment for ROP from April 2017 to January 2018. According to disease pathogenic features, the 76 eyes were divided into three groups: aggressive posterior ROP (AP-ROP) group (16 eyes), threshold ROP group (28 eyes) and type 1 pre-threshold ROP group (32 eyes). The characteristics of patients and lesions situation before the first intravitreal injection, and posttreatment fundus outcomes determined by wide-angle RetCam fundus imaging were recorded. The birth weight and postmenstrual age of first IVR treatment in AP-ROP, threshold ROP, and type 1 pre-threshold ROP groups were significant difference (1087.50±246.78, 1103.75±168.30, 1257.03±210.82 g, P=0.005; 34.50±1.46, 36.89±2.97, 36.50±2.36wk, P=0.008), while the gestational age was not difference (28.00±2.00, 28.54±1.90, 28.59±1.43wk, P=0.510). The retina hemorrhage ratio (with/without: 14/2, 8/20, 5/27), iris neovascularization or vascular engorgement ratio (with/without: 12/4, 11/17, 6/26), and the zone I (inside/outside: 16/0, 2/26, 5/27) in AP-ROP, threshold ROP, and type 1 pre-threshold ROP group were difference significantly (all P<0.05). The regression rates were 37.5%, 92.86%, and 100%, and the recurrence rates were 62.5%, 7.14%, and 0 in AP-ROP, threshold ROP, and type 1 pre-threshold ROP group, respectively (both P<0.05). The recurrence eyes were cured by secondary IVR or retinal laser photocoagulation. IVR is an effective treatment for all types of ROP. The regression of AP-ROP is significantly lower than type 1 pre-threshold and threshold disease. Birth weight, retinal hemorrhage, iris neovascularization or vascular engorgement and lesions located in zone I may be associated with AP-ROP recurrence and retreatment, which should be noted in follow-up.

Commentary: Is it time to re-evaluate the empiric intravitreal antibiotic therapy in infectious bacterial endophthalmitis?

Commentary: Is it time to re-evaluate the empiric intravitreal antibiotic therapy in infectious bacterial endophthalmitis?

Aortic stiffness and systemic inflammation changes predict clinical response to intravitreal anti-vascular endothelial growth factor therapy in patients with age-related macular degeneration.

Aortic stiffness and systemic inflammation are predictors of cardiovascular risk. Anti-vascular endothelial growth factor agents (anti-VEGF), injected intravitreally, can reverse the course of exudate age-related macular degeneration (AMD). We sought to investigate the association of changes in aortic stiffness and systemic inflammation with response to anti-VEGF therapy. 54 patients (mean age: 76 ± 10 years) with AMD received two consecutive monthly intravitreal injections of ranibizumab (0.5 mg). The primary outcome measure was change in carotid-femoral pulse wave velocity (PWV) from baseline to 1 month after the second injection. Secondary endpoint was the change in serum high sensitivity interleukin-6 (hsIL-6) levels. Ranibizumab caused a decrease of PWV after the first (by 0.36 ± 1.4 m/s) and the second injection (by 0.31 ± 1.4 m/s) and remained decreased 1 month after the second injection (overall P < 0.05). PWV decreased significantly in good responders (according to clinical criteria and fundus findings, P = 0.004), whereas it increased numerically in poor responders (P = 0.21) over the study period. In responders, hsIL-6 decreased after the first injection and remained decreased 1 month after the second injection (by 0.63 ± 0.35 pg/ml, overall P = 0.02). PWV (P = 0.005) and hsIL-6 (P = 0.042) were independent predictors of improvement after adjusting for age and presence of hypertension and diabetes. The decrease in PWV through the whole study period was positively correlated with the reduction in hsIL-6 (r = 0.36, P < 0.01). Intravitreal ranibizumab injections lead to a decrease in PWV and hsIL-6. Both parameters predict clinical improvement and may aid to improving treatment targeting and hence therapeutic outcome in patients with AMD.

Impact of Delayed Intravitreal Anti-Vascular Endothelial Growth Factor (VEGF) Therapy Due to the Coronavirus Disease Pandemic on the Prognosis of Patients with Neovascular Age-Related Macular Degeneration.

This study estimated the outcome of delayed intravitreal anti-vascular endothelial growth factor (VEGF) therapy due to the coronavirus (COVID-19) disease pandemic on the prognosis of patients with neovascular age-related macular degeneration (nAMD). This study retrospectively enrolled 57 nAMD patients whose intravitreal anti-VEGF injections were delayed for >2 weeks between February and June 2020. Best-corrected visual acuity (BCVA), central subfield thickness (CST), and anatomical characteristics were evaluated before (baseline), on the day, and at 2, 4, and 6 months after the delayed injection, and risk factors were identified. The average injection interval before and after treatment delay was 3.05 ± 1.45 and 2.41 ± 1.46 months, respectively (p = 0.002). The CST at baseline and on the day of delayed injection was 227.82 ± 62.46 and 267.26 ± 77.74 µm, respectively (p < 0.001). The average BCVA decreased from 0.29 ± 0.29 logMAR (baseline) to 0.38 ± 0.31 logMAR (6 months) (p = 0.001). The maximum subretinal fluid (SRF) height increased from 84.32 ± 89.33 µm (baseline) to 121.38 ± 103.36 µm (6 months) (p = 0.027). A higher baseline maximum SRF height was associated with less SRF height deterioration 6 months later (p < 0.001). Delayed intravitreal anti-VEGF therapy caused by the COVID-19 pandemic has worsened BCVA and residual SRF in nAMD patients after a temporary recovery. The baseline SRF reduce the degree of SRF height deterioration.

Innovator Versus Biosimilar Ranibizumab in Polypoidal Choroidal Vasculopathy: Real-World Evidence.

IntroductionTo analyze the efficacy and safety profile of the intravitreal ranibizumab biosimilar molecule, Razumab® (Intas Pharmaceuticals, Ahmedabad, India; BRm; Razumab®) and the innovator ranibizumab drug (IRm; LUCENTIS®) in Indian patients with polypoidal choroidal vasculopathy (PCV) under real-world conditions.MethodsThis was a retrospective study of treatment-naïve and previously treated PCV eyes undergoing intravitreal therapy with either BRm or IRm from January 2019 to September 2020 as three loading doses followed by a pro-re-nata (PRN) regimen. Changes in the best-corrected visual acuity (BCVA), subretinal fluid (SRF), intraretinal fluid (IRF), SRF height, and subfoveal choroidal thickness (SFCT) and the safety profiles were assessed at weeks 12, 24, and 52, respectively.ResultsA total of 22 eyes received IRm and 19 eyes underwent BRm therapy, respectively. Both the groups were comparable in age (P = 0.41) and gender distribution, although the BRm arm had significantly more eyes that were previously treated (P < 0.00001) with a greater median number of injections (P < 0.0001). At week 52, both groups had similar gains in visual acuity (P = 0.19), SRF resolution (P = 0.8), IRF resolution (P = 0.47), and SRF height (P = 0.71). The IRm eyes exhibited a significant improvement in BCVA (P = 0.001) at all visits with a greater mean number of injections (IRm: 5.41 ± 0.94; BRm: 4 ± 1.45; P = 0.0004), while the BRm eyes showed a similar increase in BCVA but did not reach statistical significance until week 52. The SFCT decreased significantly in the BRm arm at week 52 (P = 0.045). One eye (5.26%) in the BRm arm experienced mild anterior uveitis, which was treated with topical corticosteroids. In either arm, no other ocular or systemic adverse effects were observed.ConclusionsOur real-world data demonstrated the ranibizumab biosimilar Razumab to have comparable visual acuity outcomes to the innovator ranibizumab molecule with an adequate safety profile in the management of PCV. Although these encouraging results support its use as a viable alternative to the innovator molecule, further prospective studies in a diverse patient population are needed to validate our findings.

1-Year Fixed-Regimen Bevacizumab Treatment in DME-Vascular Network Image Analysis in Optical Coherence Tomography Angiography Study.

Purpose: To evaluate the effectiveness of intravitreal bevacizumab treatment in patients with diabetic macular edema (DME) by assessing retinal changes using AngioTool software (version 0.6a(02.18.14), National Cancer Institute, Bethesda, Maryland). Methods: A total of 27 eyes in patients with treatment-naïve DME were included in this prospective study. OCT-A images with a scan area of 6 × 6 mm were obtained. The DME patients with a central macular thickness (CMT) of ≥300 µm received nine bevacizumab injections within 12 months. The demographic, systemic, and ocular parameters, including the best-corrected visual acuity (BCVA) and CMT, were assessed. Explant area, vessels area, vessels percentage area, total number of junctions, total vessels length, average vessels length, the total number of endpoints, and mean lacunarity in the superficial capillary plexus (SCP) were calculated by using AngioTool software. Results: Twenty-nine eyes of DME patients were subjected to the final analysis. Bevacizumab treatment reduced CMT from 401.84 ± 84.54 µm to 328.93 ± 87.17 µm and improved BCVA from 65.18 ± 8.21 at baseline to 72.63 ± 7.43 letters among participants of the study. The anti-VEGF therapy showed no statistically significant changes in parameters calculated by AngioTool software in the study group of patients. Conclusion: The fixed-regimen intravitreal bevacizumab therapy was effective in treating DME. AngioTool software is an additional tool that could be used to assess vascular networks. However, the use of OCTA is unlikely to alter DME treatment regimens significantly or to find significant predictors. Perhaps using wide-angle devices or software will give a complete picture of the disease and prove to be more helpful.

INTERNATIONAL IMPACT OF THE COVID-19 PANDEMIC LOCKDOWN ON INTRAVITREAL THERAPY OUTCOMES: Fight Retinal Blindness Registry.

To evaluate the impact of the COVID-19 pandemic lockdowns on the outcomes of eyes treated for neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion in eight countries. A multicenter international database study of 5,782 eyes (4,708 patients) receiving intravitreal antivascular endothelial growth factor injections before, during, and after national lockdowns. The baseline visit was defined as the last visit within 3 months before lockdown, and prelockdown and postlockdown periods were defined as 6 months before and after the lockdown date. Eyes with neovascular age-related macular degeneration (n = 4,649) lost vision in all countries in proportion to the reduced number of injections. The mean visual acuity change postlockdown ranged from -0.4 to -3.8 logarithm of the minimum angle of resolution letters, and the median number of injections/visits decreased from 4-5/4-7 to 2-4/2-4 postlockdown. The diabetic macular edema (n = 654) and retinal vein occlusion (n = 479) eyes' mean visual acuity change ranged from -2.8 to +1.7 letters and -1.6 to +0.1 letters, and the median number of injections/visits decreased from 2.5-5/4-6 to 1-3/2-4 and from 3-5.5/4-5 to 1-3.5/2-3.5, respectively. The 6-month dropout rates postlockdown were 20% for neovascular age-related macular degeneration, 27% for diabetic macular edema, and 28% for retinal vein occlusion. This international study provides estimates of the impact of COVID-19 pandemic lockdown on intravitreal therapy and suggests that prioritizing neovascular age-related macular degeneration eyes seems appropriate.

Examining the Relationship Between Diabetic Macular Edema, and Obstructive Sleep Apnea

PurposeThis prospective cohort study examined the relationship between diabetic macular edema (DME), diabetic retinopathy (DR) and obstructive sleep apnea (OSA) in patients after 1 year of treatment with anti-VEGF injection and/or continuous positive airway pressure (CPAP).Patients and MethodsThe study included adults with type 1 or 2 diabetes mellitus with diabetic retinopathy. Polysomnography metrics were measured at baseline. Ophthalmologic metrics were measured at baseline, six-month (6m) and twelve-month (12m) follow-up. All DME+ patients received standard care, and all OSA+ patients were advised continuous positive airway pressure (CPAP). Logistic regression between DR severity and OSA severity was performed. Analysis of variance (ANOVA) was performed between subgroups.ResultsSeventy-four eyes of 49 patients with DR were included. Prevalence of OSA was significantly higher in the DME+ group (70.7%) than DME- group (42.4%, p < 0.05). A significantly lower average minimum SaO2 was noted in OSA+DME+ (81.74%) than OSA+DME- eyes (88.23%, p < 0.05). Logistic regression analysis of ophthalmological and sleep metrics showed no correlation between DR and OSA severity. CPAP adherence was 20% (6/30) in the OSA+DME+ cohort and 36% (5/14) in the OSA+DME- cohort. At 12m, CPAP-adherent OSA+DME+ showed significantly lower DR severity score (1.00 ± 0.0) than CPAP non-adherent OSA+DME+ (1.36 ± 0.80, p = 0.042). No significant patterns were noted for visual acuity and mean central retinal thickness.ConclusionDME is associated with the presence of OSA. Minimum SaO2 is a significant OSA clinical variable for DME. DR severity is not associated with OSA severity. CPAP coupled with intravitreal anti-VEGF therapy may be helpful for reducing DR severity in DME+ eyes. Presence of OSA may diminish intravitreal anti-VEGF efficacy on anatomical (mean CRT) and functional (VA) outcomes of DME.

Synergistic Effect of Combined Sub-Tenon Triamcinolone and Intravitreal Anti-VEGF Therapy for Uveitic Macular Edema.

PurposeTo investigate effects of intravitreal anti-VEGF in combination therapy with sub-Tenon triamcinolone acetonide (STA) injection for uveitic macular edema (UME).DesignA single-center, retrospective cohort study.MethodsThe medical records were obtained for 65 eyes of 65 patients with UME. Of which, 32 eyes received combined anti-VEGF with STA injection, and 33 eyes received 40 mg of STA injection alone. The primary outcome was the reduction of central macular thickness (CMT) measured with optical coherence tomography (OCT). Resolution rate of clinical UME and changes of best corrected visual acuity (BCVA) over 24 weeks were secondary outcomes.ResultsThere was a significantly greater reduction of CMT with the combination treatment than with STA alone at 1-week (β = −157.9, P < 0.001) and 1-month (β = −53.1, P = 0.019) after injection. The cumulative incidence of macular edema resolution of all eyes was 87.7%, with 90.6% (29/32) in the combined group and 84.8% (28/33) in the STA group, respectively. More incidence of UME resolution was observed in the combined group than the STA group after 1 week (71.9% vs 15.2%, P < 0.001) and 4 weeks (84.4% vs 54.5%, P = 0.009), respectively. BCVA was better for the combination treatment than STA alone at 1-week (β = −0.085, P = 0.070) and 1-month (β = −0.108, P = 0.019) after injection, respectively. Increased intraocular pressure (>25 mmHg) was observed in 4 eyes (12.5%) in the combined group and 5 eyes (15.2%) in the STA group, respectively.ConclusionCombined intravitreal anti-VEGF and STA is superior to STA alone for reduction of UME and visual restoration. Addition of anti-VEGF did not increase risk for steroid-induced elevation of intraocular pressure over 6 months.

Short-term and long-term results after intravitreal bevacizumab therapy for macular oedema in branch retinal vein occlusion.

Objectives: The aim of this study was to determine the possible correlation between the short- and long-term effects of intravitreal bevacizumab on macular oedema after branch retinal vein occlusion (BRVO).Material and methods: This prospective clinical study included fifteen eyes of patients with macular oedema after BRVO. Corrected distance visual acuity (CDVA), recorded in LogMAR units, central foveal thickness (CFT) and maximum foveal thickness (MFT) were evaluated at one month after first application and at least every 2 months for one year. PRN treatment protocol was used for all patients. Statistical calculation was performed with SPSS for Windows and Microsoft Excel.Results: Mean CFT decreased significantly (p<0,0001) from baseline 471,2 ± 151,7 μm to 285,9 ± 79,82 μm at 12 months. CDVA improved significantly (p<0,0001) from baseline 0,58 ± 0,34 to 0,1 ± 0,25 at the end of follow up period. Change from baseline in the CDVA after one month was significantly positively correlated with the change in CDVA after 12 months (r=0,76, p=0,001). Change in CFT after one month had a strong positive correlation (r=0,78, p=0,001) with change after 12 months. There was no statistically significant correlation between the number of injections and the changes in CDVA, CFT, MFT after a single injection.Conclusions: Single injection effects of bevacizumab may indicate long-term results on macular oedema after BRVO, but further and larger studies are necessary.Abbreviations: BRVO = Branch retinal vein occlusion, RVO = Retinal vein occlusion, CFT = Central foveal thickness, MFT = Maximum foveal thickness, VEGF = Vascular endothelial growth factor, MO = Macular oedema, CDVA = Corrected distance visual acuity, PRN = Pro-re-Nata, SD-OCT = Special-domain optical coherence tomography, FT = Foveal thickness, LogMAR = Logarithm of the Minimum Angle of Resolution, WHO = World Health Organization, RPE = Retinal pigment epithelium