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Purpose: Limited data is available on treatment satisfaction with the management of wet age-related macular degeneration (wAMD) among patients in Italy. In this cross-sectional real-world study, treatment satisfaction with anti-vascular endothelial growth factor (anti-VEGFs) was assessed in patients with wAMD in Italy. Patients and Methods: This was a non-interventional, cross-sectional survey involving patients with wAMD receiving anti-VEGFs. The survey was administered through a virtual assistant via phone. Patients' treatment satisfaction was assessed using a newly developed Novartis Tailored Treatment Satisfaction Questionnaire (NVS TTSQ) and the validated Macular Disease Treatment Satisfaction Questionnaire (MacTSQ). Results: Overall, 154 evaluable patients were enrolled in 5 centers across Italy. The mean (SD) age of the patients was 76.8 years (7.01). Overall treatment satisfaction score assessed by NVS TTSQ was 40.50 (7.11), with a mean of 9.97 (1.84) on the information domain and 22.98 (4.57) on the unmet need domain. Patients were satisfied with diagnosis communication (4.99 [1.30]), information provided on treatment administration (4.58 [1.49], range 0– 6), the waiting room (4.40 [1.43]), and management of visits and injections at the center (5.14 [1.12]), general management of maculopathy at the center (5.22 [1.01]). Patients were not satisfied with their independence in terms of disease management (2.56 [2.45]); they would like additional information about the disease (5.38 [1.03]) and to discuss the injection procedures (4.02 [1.94]) with already-treated patients. The overall treatment satisfaction score on MacTSQ scale was 55.84 (10.13). Conclusion: Patients with wAMD are satisfied with the overall management of their disease in Italy. However, patients would like to have more information on prognosis and management of the disease. [ABSTRACT FROM AUTHOR]

Purpose: To assess ocular pain in patients undergoing multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) who have previous factors that may influence pain sensitivity. Methodology: This is a prospective, observational, case series study involving patients who underwent multiple (≥ 3) pro re nata intravitreal injections of ranibizumab or aflibercept to treat any cause of chorioretinal vascular disease. Ocular pain was assessed by the numerical analog scale during intravitreal injection. For this study, the main variable was ocular pain and the secondary variables included age, sex, previous history of glaucoma, primary retinal vascular disease, severe dry eye history, trigeminal pain, scleral buckle surgery, collagen diseases, fibromyalgia, severe migraine history, pars plana vitrectomy, scleral thickness measurements, and type of anti-VEGF. Results: In a total of 894 patients, 948 eyes (4822 intravitreal injections), 793 patients (88.6%) had ocular pain sensitivity between no pain to mild pain, 80 patients (8.9%) had moderate ocular pain, 15 patients (1.6%) had severe ocular pain, and 6 patients (0.7%) had extremely severe ocular pain. Patients with severe dry eye (p = 0.01) and previous history of scleral buckle surgery (p = 0.01) showed a significant correlation with ocular pain during intravitreal injection. Pars plana scleral thickness (> 550 um) and diabetic neuropathy were associated with ocular pain but did not meet the criteria for statistical significance (p = 0.09 and p = 0.06, respectively). Conclusion: Dry eye and prior scleral buckle surgery may contribute to pain associated with intravitreal injection. These issues should be taken into consideration in patients undergoing multiple intravitreal injections. [ABSTRACT FROM AUTHOR]

Purpose: Interleukin-8 (IL-8) is a potent pro-angiogenic and pro-inflammatory chemokine, suggested to hold a role in neovascular age-related macular degeneration (nAMD). Our aim is to study the association of the single-nucleotide polymorphism − 251 A/T (rs4073) in the IL-8 promoter region with the treatment response to intravitreal anti-vascular endothelial growth factor (VEGF) injections in nAMD. Patients and Methods: This is a prospective study of treatment-naïve patients with nAMD. Treatment response after a loading dose of three intravitreal anti-VEGF injections was defined as functional response based on change in visual acuity, and morphological response based on change in central retinal thickness (CRT) and intraretinal fluid on optical coherence tomography. Morphological response was categorized in good, partial, and poor responders. Blood DNA was analyzed for − 251 A/T genotype. Results: The IL-8 promoter polymorphism − 251 A/T was not significantly associated to functional treatment response (P=0.09). No significant association was found between genotype and morphological treatment response (P=0.799). Older age was significantly associated to good morphological responders compared to partial and poor responders (P=0.014). Conclusion: The IL-8 polymorphism − 251 A/T is not associated to morphological nor functional treatment response to intravitreal anti-VEGF injections in patients with nAMD. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of faricimab injections for treatment-naïve neovascular age-related macular degeneration (nvAMD) patients, including subtypes and pachychoroid phenotypes, and identify predictive factors for visual outcomes. Methods: nvAMD patients were prospectively recruited, receiving three monthly faricimab (6 mg) injections. Best-corrected visual acuity (BCVA) two months after the last injection (month 4) was compared between subtypes, and between pachychoroid neovasculopathy (PNV) and non-PNV eyes. Regression analysis determined factors influencing month 4 BCVA. Results: The study involved 23 patients (12 typical AMD [tAMD], 10 polypoidal choroidal vasculopathy [PCV], 1 retinal angiomatous proliferation [RAP]). Eleven exhibited PNV phenotype. Significant BCVA (P = 4.9 × 10− 4) and central retinal thickness (CRT) (P = 1.3 × 10− 5) improvements were observed post-faricimab treatment. The therapy demonstrated favourable results for both tAMD and PCV eyes, and non-PNV and PNV eyes. Faricimab achieved dry macula in 77.3% of eyes, with subretinal fluid resolution in most cases, although intraretinal fluid (IRF) often persisted. Multivariable analysis identified external limiting membrane (ELM) presence and IRF as BCVA contributors at month 4. Conclusion: Faricimab demonstrated significant effectiveness and safety in treatment-naïve nvAMD patients, particularly for PCV and PNV eyes. ELM presence and IRF is predictive of visual outcomes. [ABSTRACT FROM AUTHOR]

To assess the functional and anatomical effects of transitioning to conbercept intravitreal injection (IVC) treatment in patients with diabetic macular edema (DME) who had inadequate responses to prior anti-vascular endothelial growth factor (anti-VEGF) injections.Methods: We retrospectively included eyes with persistent DME after at least 3 injections of intravitreal ranibizumab (IVR). The analysis included the assessment of best corrected visual acuity (BCVA) and central macular thickness (CMT) during 6 months after the switch.Results: A total of 30 patients (30 eyes) were included. CMT dropped sharply from 437.8± 40.67μm at baseline to 363.59± 45.09,312.52 ± 39.15, 278.51 ± 37.92, and 292.59 ± 38.09 after 1, 2, 3 and 6 months of IVC, respectively (p < 0.001). BCVA in log MAR units was significantly improved from 0.73± 0.15 at baseline to 0.50± 0.09,0.46± 0.72, 0.40± 0.06 and 0.48± 0.04 after 1, 2, 3 and 6 months, respectively (p < 0.001).Conclusion: Switching to Conbercept effectively improved visual and anatomical structure in DME patients who had not responded satisfactorily to previous anti-VEGF injections. [ABSTRACT FROM AUTHOR]

We evaluate the visual and anatomic efficacy of brolucizumab, examine changes in treatment intervals after switching to brolucizumab, and estimate the incidence of drug-related adverse events in the real world.Design, Setting, and Participants: This was a retrospective consecutive case series of 626 eyes (543 patients) with nvAMD treated with 1438 brolucizumab injections at a single retina practice between 10/1/2019 and 5/15/2020.Main Outcomes and Measures: Changes in visual acuity (VA); anatomic outcomes assessed by optical coherence tomography (OCT) including central subfield thickness (CST), macular volume (MV), presence of intraretinal fluid (IRF), subretinal fluid (SRF), and serous pigment epithelial detachment (sPED) on foveal line scans; treatment intervals before and after receiving brolucizumab; and the incidence of brolucizumab-related adverse events.Results: The majority of eyes (N = 531, 89.7%) had received prior anti-VEGF therapy with aflibercept, ranibizumab, and/or bevacizumab. VA improved in treatment-naïve eyes (+3.7 letters, p = 0.04), and was maintained in previously treated eyes. There were significant improvements in all anatomic outcomes in both groups (p < 0.001). We observed a 4.8% incidence of intraocular inflammation (IOI) and a 0.6% incidence of retinal vasculitis. The average treatment interval increased from 6.3 to 6.8 weeks (p = 0.001).Conclusions and Relevance: Brolucizumab treatment was associated with VA improvement in naïve eyes and maintenance of VA in previously treated eyes. Switching to brolucizumab was associated with improved anatomic outcomes and extended treatment intervals in most eyes. We observed a similar incidence of IOI and a lower incidence of retinal vasculitis compared to the Safety Review Committee's analysis of HAWK and HARRIER. [ABSTRACT FROM AUTHOR]

This review aimed to systematically compare the efficacy and safety of intravitreal aflibercept (IVA) and vitrectomy for treating severe vitreous hemorrhage (VH) secondary to proliferative diabetic retinopathy (PDR). The review was conducted in accordance with PRISMA guidelines. A search strategy, including the MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and US National Library of Medicine databases, was developed to identify randomized controlled trials (RCTs) that compared vitrectomy and IVA for managing VH due to PDR (participant age ≥ 18 years). The primary outcome measure was the difference in the mean visual acuity between the two treatment groups at 1, 6, and 24 months. Outcome measures included clearance of VH (in weeks), the incidence of recurrent VH, and the rate of complications. The studies were evaluated using the Cochrane Bias (ROB) tool. We identified 774 articles; six articles met the inclusion criteria, and two were ultimately included (n = 239 eyes). With or without PRP, IVA injections and vitrectomy were performed in 117 and 122 eyes, respectively. The mean BCVA at one month was significantly better in the vitrectomy group (MD=0.22, CI:0.10– 0.34, p=0.0003), but no difference was found at six months (MD=0.04, CI: − 0.04– 0.12, p=0.356). The incidence of recurrent VH was significantly higher in the IVA group (OR=5.05, CI:2.71– 9.42, p< 0.0001). The probability of recurrent VH was five times greater in the IVA group than that in the vitrectomy group. There were no significant differences in the overall proportions of intra- or postoperative complications (OR=0.64, CI: 0.09– 4.85, p=0.669). None of the studies had a low ROB in any of the seven domains. We conclude that IVA can be considered a viable treatment modality for diabetic VH in patients with a good follow-up. Vitrectomy initially provides better visual effect, faster VH recovery, and lower VH recurrence than IVA injections. [ABSTRACT FROM AUTHOR]

To evaluate the short-term effectiveness and safety outcomes following brolucizumab treatment in patients with neovascular age-related macular degeneration (nAMD) as a part of real-world clinical practice in India.Methods: This was a retrospective, observational, multicentre study including patients (≥ 50 years old) diagnosed with nAMD. Anonymized data of the patients receiving the first dose of brolucizumab intravitreal injection (IVI) who were either treatment-naïve or previously treated with a single or a combination of other anti-VEGF IVIs were included. The present study reported the change in retinal fluid levels from baseline to month 3, best-corrected visual acuity (BCVA), central retinal thickness (CRT), and the number of injections received. The adverse events in the three months after brolucizumab treatment initiation were also monitored.Results: The study included 63 patients (65 eyes) from four study centres across India (mean age: 69.1 ± 9.7 years). A total of 82 brolucizumab injections were administered during the 3 months of study duration, with 52/65 (80.0%) eyes receiving only 1 injection. Resolution of IRF, SRF, and PED was observed in 76.9%, 64.6%, and 67.7% of eyes, respectively. Further, a significant reduction in CRT was observed (baseline: 403.5 ± 118.7 μm; month 3: 308.3 ± 73.8 μm; p < 0.001), and BCVA also improved notably from 0.7 ± 0.5 logMAR at baseline to 0.5 ± 0.4 logMAR at month 3 (p < 0.001). Adverse events (AEs) were reported in 3 eyes from 3 patients; retinal pigment epithelial rip (1) and subretinal hemorrhage (2) after the first injection of brolucizumab, however, none discontinued the treatment.Conclusion: The study reports on the short-term effectiveness and tolerability of brolucizumab therapy in the management of nAMD in both treatment-naïve and switch eyes. Brolucizumab was observed to have a favourable benefit-risk profile, and study results were within the known safety profile, with no instances of intraocular inflammation. [ABSTRACT FROM AUTHOR]

Purpose: To study the effects of intravitreal injection (IVI) of anti-VEGF (vascular endothelial growth factor) agents on intraocular pressure (IOP) and find associations with acute pressure spikes. Methods: This was a three-month, prospective study of patients receiving outpatient IVI of anti-VEGF agents for diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO) at the Acuity Eye Group Medical Centers. IOP was measured pre- and post-injection at 10-minute intervals up to 50 minutes after injection with a handheld tonometer. Patients with an IOP greater than 35 mmHg at 30 minutes received an anterior chamber paracentesis (ACP), while patients below 35 mmHg were monitored without intervention. Results: A total of 617 patients (51% female, 49% male) received IVI for DR (n = 199), AMD (n = 355), and RVO (n = 63). ACP was performed in 17 patients. Average pre-injection IOP was 16 ± 4 compared to 24 ± 7 mmHg for the non-ACP vs ACP group, respectively (mean ± standard deviation), p < 0.0001. IOP returned to baseline in 98% of patients at 50 minutes. A diagnosis of glaucoma and glaucoma suspect was more prevalent in the ACP group compared to the non-ACP group, 82.3% vs 14.2% and 17.6% vs 9.0%, respectively, p < 0.0001 and p > 0.05. Patients with a pre-injection IOP > 25 mmHg and a history of glaucoma had a 58.3% rate of ACP. A 31-gauge needle had a higher mean increase in IOP from baseline compared to 30-gauge needle, p < 0.0001. Conclusion: IOP spikes are most significant in the first 10 minutes after IVI but typically resolve within the first hour. However, utilizing a smaller 31-gauge IVI in patients with a glaucoma history and pre-injection IOP > 25 mmHg may be associated with significant IOP spikes lasting longer than 30 minutes. [ABSTRACT FROM AUTHOR]

Purpose: Ocular vascular diseases are common causes of visual impairment and blindness, for which anti-vascular endothelial growth factor (anti-VEGF) is the first-line therapy. Current study describes the profile of patients receiving intravitreal anti-VEGF injections (IVI), and gender variation in Bhutan. The study was designed to inform national health policy. Study Design: Retrospective cross-sectional study. Methods: We reviewed the surgical registers of the vitreoretinal (VR) units across Bhutan over three years. Patient demography, clinical findings, diagnostic tests performed, and diagnoses or indications for IVI were logged. A descriptive analysis was performed. Results: Despite limited availability of anti-VEGF, a total of 381 patients received IVI in operating theatres as mandated by the national guidelines. The majority of patients were males (230, 60.4%, p = 0.004). The mean age was 65.2 ± 13.5 years (range 13 years to 90 years), and a median of 69 years. The majority of the treated eyes (117, 30.7%) had BCVA < 3/60 to light perception (PL), and another 51 eyes (13.4%) had < 6/60 to 3/60. The most common indication for IVI was neovascular age-related macular degeneration (nAMD) (168 cases, 42.2%), followed by retinal vein occlusion (RVO) (132 cases, 34.6%), diabetic macular oedema (DMO) and retinopathy (DR) (50 cases, 13.1%), and myopic choroidal neovascular membrane (11 cases, 0.03%). Conclusion: Limited human resources for managing VR diseases in Bhutan are compounded by economic and geographic challenges. With increasing VR diseases such as nAMD and myopia and complications of systemic diseases such as DR, DMO and RVO, there is a need to improve VR services. Currently, anti-VEGF is procured only for a pooled patients requiring IVI, and patients are lost due to longer waiting periods. Bhutan needs to assess if females are reporting less or are not receiving treatment due to cultural barriers and social stigma. [ABSTRACT FROM AUTHOR]

Purpose: To analyse outcomes of innovator ranibizumab (IRM) (Lucentis) and biosimilar ranibizumab (BRM) (Razumab) in Indian eyes with neovascular age-related macular degeneration (nAMD). Methods: Retrospective observational study in nAMD patients, who were treated with IRM or BRM (3 loading doses followed by pro re nata (PRN). Primary outcome measures were change in best corrected visual acuity (BCVA) and central macular thickness (CMT) along with safety analysis. Secondary outcomes measures were changes in the subretinal fluid (SRF) and intraretinal fluid (IRF). Results: Inclusion criteria were satisfied in 164 eyes (60.74%). A total of 87 eyes were treated with IRM, and 77 eyes received BRM. Baseline BCVA was 0.57± 0.27 logMAR in IRM group and 0.61± 0.25 in the BRM group. At 3, 6, 9, and 12 months BCVA was 0.27± 0.22 (p< 0.0001), 0.34± 0.23 (p< 0.0001), 0.39± 0.25 (p< 0.0001), and 12 months 0.41± 0.23 (p< 0.0001) in the IRM group and 0.24± 0.16 (p< 0.0001), 0.27± 0.16 (p< 0.0001), 0.34± 0.17 (p< 0.0001), 0.38± 0.18 (p< 0.0001) in the BRM group. Baseline CMT was 420.39± 54.45 μm in IRM group and 407.82± 53.07 μm in BRM group. At 3, 6, 9, and 12 months, CMT decreased to 258.28± 20.4 μm (p< 0.0001), 268.38± 19.5 μm (p< 0.0001), 269.51± 32.41 μm (p< 0.0001), and 278.28± 16.56 μm (p< 0.0001) in the IRM group and 258.84± 17.47 μm (p< 0.0001), 265.69± 17.29 μm (p< 0.0001), 273.64± 23.13 μm (p< 0.0001), and 283.09± 19.66 μm (p< 0.0001) in the BRM group. Similar improvements in IRF and SRF levels in the patients were noted in both groups. Required number of doses of IRM and BRM was similar over the 12 month period in both groups. A similar profile of adverse events was noted in both the groups. Conclusion: Intravitreal injection of IRM and BRM show similar efficacy and safety in Indian eyes with nAMD. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity (ROP) is a vasoproliferative disorder with an imminent risk of blindness, in cases where early diagnosis and treatment are not performed. The doctors' constant motivation to give these fragile beings a chance at life with optimal visual acuity has never stopped, since Terry first described this condition. Thus, throughout time, several specific advancements have been made in the management of ROP. Apart from the most known risk factors, this narrative review brings to light the latest research about new potential risk factors, such as: proteinuria, insulin-like growth factor 1 (IGF-1) and blood transfusions. Digital imaging has revolutionized the management of retinal pathologies, and it is more and more used in identifying and staging ROP, particularly in the disadvantaged regions by the means of telescreening. Moreover, optical coherence tomography (OCT) and automated diagnostic tools based on deep learning offer new perspectives on the ROP diagnosis. The new therapeutical trend based on the use of anti-VEGF agents is increasingly used in the treatment of ROP patients, and recent research sustains the theory according to which these agents do not interfere with the neurodevelopment of premature babies. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate real-world experience using intravitreal brolucizumab (IVBr), alone or in combination with aflibercept, in eyes with neovascular age-related macular degeneration (nAMD) treated previously with other inhibitors of VEGF (anti-VEGF). Methods: This was a retrospective study of all eyes with nAMD treated with IVBr on a treat-and-extend protocol at a single center. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) at baseline and final visit, and drug-related adverse events were analyzed. Eyes with recurrent macular fluid on IVBr every 8 weeks were treated with a combination therapy alternating between IVBr and aflibercept every month. Results: Among 52 eyes (40 patients) on IVBr, all had been previously treated with other anti-VEGF therapy, with 73% having persistent macular fluid. After a mean follow-up of 46.2± 27.4 weeks on IVBr, the mean treatment interval for intravitreal therapy increased to 8.8± 2.1 weeks on IVBr from a baseline of 6.1± 3.1 weeks (p< 0.001). Macular fluid decreased and BCVA was stable/improved in 61.5% of eyes on IVBr. Ten eyes with increased macular fluid on IVBr monotherapy when extended to every 8 weeks were treated with combination therapy alternating between IVBr and aflibercept every 4 weeks. In these eyes, 80% had improved macular fluid on OCT and 70% stable or improved BCVA after a median follow-up of 53 weeks on combination therapy. Mild intraocular inflammation developed in four eyes, all occurring on IVBr monotherapy, and none had associated vision loss. Conclusion: In the real world, IVBr used to treat eyes with nAMD previously treated with other anti-VEGF therapies appears to be well tolerated and associated with an improvement in macular fluid, stabilization of BCVA, and/or increase in intravitreal treatment interval. Combination therapy alternating between IVBr and aflibercept monthly appears to be well tolerated and can be considered for eyes with macular fluid on IVBr every 8 weeks. [ABSTRACT FROM AUTHOR]

Purpose: To determine the reported rates of intraocular inflammation (IOI) in patients treated with intravitreal aflibercept (IVT-AFL) 2 mg in routine clinical practice (ie, outside interventional studies), across all indications and within all countries (excluding the United States), with access to either the vial presentation or pre-filled syringe (PFS). Patients and methods: A search was conducted using the Bayer EYLEA® Global Safety Pharmacovigilance Database for reported cases of IOI and IVT-AFL use between October 2012 and March 31, 2022. Results: With more than 10 years of post-marketing experience with the IVT-AFL vial presentation (> 25 million sold units), and over 2 years of experience with the PFS of IVT-AFL (> 6.7 million sold units) the rate of any IOI, including endophthalmitis, outside the United States was 0.3 events per 10,000 units for the PFS and 1.2 events per 10,000 units for the vial presentation. The event rates specifically for endophthalmitis were 0.1 per 10,000 units for the IVT-AFL PFS and 0.6 per  10,000 units for the IVT-AFL vial presentation. Conclusion: In patients with retinal diseases treated in routine clinical practice with IVT-AFL either from a vial or the PFS, medically important adverse events of IOI, and in particular, endophthalmitis, are infrequently reported events. Numerically, reported rates of IOI and endophthalmitis are low for the vial presentation and even lower for the PFS. [ABSTRACT FROM AUTHOR]

Purpose: To compare the PRN anti-VEGF injection patterns of four retina specialists with respect to the visual and anatomic outcomes in the management of wet age-related macular degeneration (AMD). Methods: Medical records of patients who received bevacizumab, ranibizumab, and aflibercept anti-VEGF injections (years 2010– 2020) by four retina specialists were reviewed for frequency, injection intervals, best corrected visual acuity (BCVA), and central macular thickness, center involved (CMT) for statistical analysis. Outcomes measured were change in logMAR BCVA and CMT from the first to last injection visit. Results: Out of 137 AMD patients, 172 eyes were injected by four retina specialists in PRN fashion. Although all four specialists started the injection at similar baseline BCVA and CMT (p > 0.1), significant differences in mean injection number (9.0, p = 0.0001), injection intervals (5.06 weeks, p = 0.001), and total length of treatments (53.3 weeks, p = 0.0001) were observed. The mean change in logMAR BCVA between the first and last injection was − 0.05, − 0.22, 0.07, and 0.06 for the four specialists, respectively (p = 0.031), and the mean change in CMT was – 53.3, − 41.4, − 72.7, and − 21.9 μm (p = 0.41), respectively. Conclusion: Despite similar baseline criteria for injections by the retina specialists, different anti-VEGF injection regimens were practiced resulting in variations in BCVA and CMT outcomes. This suggests a need in establishing a universally adoptable injection regimen with possible integration of the confounding factors to reduce burden on both patients and retina specialists. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is considered one of the leading causes of vision loss globally. It principally causes upregulation of pro-angiogenic, proinflammatory, and vascular permeability factors such as vascular endothelial growth factor (VEGF), leading to neovascularisation. The advanced stage of DR or proliferative diabetic retinopathy (PDR) is of more concern, as it leads to vitreous haemorrhage and traction retinal detachment. Various risk factors associated with PDR include hyperglycemia, hypertension, neuropathy, dyslipidemia, anaemia, nephropathy, and retinal complications of drugs used for diabetes. Current management approaches for PDR have been stratified and involve pan-retinal photocoagulation, vitrectomy, and anti-VEGF agents. Given the emerging role of anti-VEGF agents as a favourable adjunct or alternative therapy, they have a critical role in the management of PDR. The review emphasises current management approaches for PDR focusing on anti-VEGF therapy. The review also highlights the risk/benefit evaluation of the various approaches employed for PDR management in various clinical scenarios. [ABSTRACT FROM AUTHOR]

Purpose: To describe a case of hypotony maculopathy following anti-VEGF intravitreal injection (IVI) in a patient with pseudoxanthoma elasticum (PE). Methods: Clinical case report. Results: A 52-year-old male complained of right eye (OD) vision loss 2 days after an uncomplicated anti-VEGF IVI for the treatment of choroidal neovascularization secondary to angioid streaks. Relevant medical history included PE, pathologic myopia, and a previous pars plana vitrectomy (PPV) due to a retinal detachment. OD best-corrected visual acuity (BCVA) dropped from 6/12 to 6/18 after the IVI. Intraocular pressure (IOP) was 3 mmHg and chorioretinal folds were evident in the posterior pole. Topical dexamethasone and atropine were prescribed, and full recovery was noticed after 3 days. Four months later, the patient developed a new episode of vision loss after another IVI. His BCVA was counting fingers, IOP was 2mmHg, and more noticeable chorioretinal folds were found. This time, an open scleral wound at the injection site was evident and a scleral suture was necessary. Once again, the patient recovered well. Conclusion: Hypotony maculopathy following intravitreal injection is a rare condition. However, the described patient presented several conditions which could be related with poor scleral wound closure: intrinsic scleral fragility due to myopia and pseudoxanthoma elasticum; repeated IVI procedures; and absence of vitreous in the posterior segment due to prior vitrectomy. Despite the good outcome, hypotony maculopathy may be a sight-threatening condition, and special attention is necessary for specific patients with risk factors. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study comprised the anatomical and functional assessment of the optic nerves and macular ganglion cells in the population of patients with unilateral wet age-related macular degeneration (wAMD) and comparison of its results to those obtained from the fellow eye with non-advanced dry age-related macular degeneration (dAMD). Furthermore, we aimed to determine if the number of administered injections contributed to the potential differences between the examined eyes. Methods: The study was based on 104 eyes of 52 patients in a cross-sectional study. The eyes with chronically treated wAMD were the main subject of the study, while fellow eyes affected with non-advanced dAMD served as the control group. Primary morphological outcomes comprised differences in peripapillary retinal nerve fiber layer (RNFL) and GCC layers between the studied groups (treated and control). In turn, primary functional outcomes included differences in implicit times and amplitudes of the P100 wave of pattern visual evoked potentials (PVEP) and N95 wave of pattern electroretinogram (PERG) between treated and control groups. Results: We did not find any differences in total RNFL thickness between wAMD and dAMD groups. The number of injections only affected the RNFL in the nasal quadrant of the optic disc (p = 0.023). We did not find any differences regarding GCL thickness in both groups. In the study group, a longer implicit time of the P100 of PVEP (p = 0.014) and a shorter amplitude of the P50-N95 wave of PERG (p = 0.005) were detected. The total number of injections had no significant effect on these two values. Conclusion: We detected worse functional parameters of the optic nerve and retinal ganglion cells in eyes with wAMD, with lack of significant differences in anatomical (RNFL, GCL) parameters compared to the control group. However, the number of injections did not contribute to the differences found. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the safety and efficacy of micropulse (MP) macular laser in combination with intravitreal aflibercept for the treatment of center-involved diabetic macular edema (CI-DME). Methods: A single-blind prospective randomized controlled pilot trial was performed. In total, 30 eyes of 30 patients with CI-DME and best corrected visual acuity (BCVA) between, and including, 20/30 and 20/400 were enrolled. Enrolled eyes were randomized to 2 groups. Group 1 received intravitreal aflibercept injections (IVT-AFL) with sham laser. Group 2 received IVT-AFL with MP laser. Both groups were followed every 4 weeks for 48 weeks and retreatment was performed on pro re nata basis according to preset criteria. The main outcome measure was the average number of intravitreal injections for each group at 48 weeks. Secondary outcome measures included changes in BCVA and central macular thickness (CMT) at 24 and 48 weeks. Results: The average number of intravitreal injections at 48 weeks was similar between the groups (8.5± 3.3 in Group 1 vs 7.9± 3.6 in Group 2, p=0.61). After 48 weeks, both groups demonstrated an improvement in BCVA and CMT. However, the difference in improvement between the groups was not statistically significant (p=0.18 for BCVA and p=0.57 for CMT). Conclusion: Intravitreal injections of aflibercept led to improvements in BCVA and CMT at 24 and 48 weeks. Addition of MP laser to eyes in group 2 did not offer additional benefit in reducing treatment burden or improving CMT. Eyes that received MP laser showed a numerically greater improvement in BCVA, although this was not statistically significant. Clinicaltrials.gov Identifier: NCT03143192 March 8, 2017. [ABSTRACT FROM AUTHOR]

Purpose: This 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 Methods: The 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. Results: Seventy-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. Conclusion: DME 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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of intravitreal aflibercept injection (IAI) for vitrectomized eyes with diabetic macular edema (DME) at two years. Methods: This is a prospective, non-comparative, multicenter observational study including diabetic patients with visual acuity between 20/400 to 20/40 due to DME, who have undergone vitrectomy at least 3 months before the first aflibercept injection. Treatment protocol included 5 monthly aflibercept injection followed by a ProReNata regimen during the first year. Participants were managed at clinicians' discretion using Treat and Extend or Observe and Plan regimen during the second year. Visual acuity, OCT findings and number of IAI were assessed at two years. Results: Available data for 28 eyes with DME previously vitrectomized treated with aflibercept intravitreal injection during at least 2 years were collected. Visual gain was +5.4 letters (p = 0.01), and central macular thickness decreased significantly − 62μm, p < 0.001) at 2 years. Resolution of macular edema allowing discontinuation of aflibercept was observed in 7 eyes (15%). Mean number of injections was 14.6, and mean interval injection was 6.4 weeks for 2 years. Conclusion: These results suggest that IAI is beneficial in vitrectomized eyes leading to improvement of visual and anatomical outcome which was maintained for 2 years. [ABSTRACT FROM AUTHOR]

Neovascular age-related macular degeneration (nAMD) is a common world-wide cause of visual loss. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are an effective means to treat nAMD and reduce its impact on vision compared to either sham treatment or photodynamic therapy. Currently, the approved anti-VEGF drugs include ranibizumab, aflibercept and brolucizumab. In addition, bevacizumab, used as an off-label drug, and has been shown to be effective in treating nAMD. While anti-VEGF agents are effective, its limitations include the requirement for frequent, often monthly injections, and the need for long-term treatment of nAMD. These present significant burdens on the healthcare system and on the patients. In addition, reviews of patients with nAMD treated with anti-VEGF have reported deterioration of vision over time with progression of geographic atrophy. These limitations are partly addressed by exploring different treatment regimens that reduce the frequency of treatments. Newer anti-VEGF drugs have been shown in Phase III clinical trials to have injection intervals as long as 12 or even 16 weeks for a proportion of patients. There is research on newer drugs that affect other pathways, such as the angiopoietin pathway, which may impact nAMD by extending the treatment interval and reducing the burden of treatment. Other measures include the use of sustained-release implants that release the drug regularly over a period of time, and can be refilled periodically, as well as hydrogel platforms that serve to release the drug. The use of biosimilars will also serve to reduce the cost of treatment for nAMD. A new frontier of gene therapy, primarily targeting genes involved in the transduction of retinal cells to produce anti-VEGF proteins intraocularly, also opens a new avenue of therapeutic approaches that can be used for treatment. This review paper will discuss both current treatment options and the newer treatments under development. [ABSTRACT FROM AUTHOR]

Purpose: To detect the impact of intravitreal injection (IVI) therapy with sole anti-vascular-endothelial-growth-factor (VEGF) or combined with steroids treating diabetic macular edema (DME) on activity of proliferative diabetic retinopathy (PDR) based on total number of panretinal photocoagulation (PRP) spots needed within 2 years. Patients and Methods: A retrospective study of 102 eyes with primary-onset PDR and minimum follow-up of 24 months divided into 2 groups: Group 1 (G1) 40 eyes received only PRP and did not develop DME. Group 2 (G2) 62 eyes received additional IVI-therapy due to concomitant DME, with anti-VEGF only (subgroup 2a, G2a) or in combination with steroids (subgroup 2b, G2b). Main outcomes: central macular thickness (CMT, μm), best-corrected visual acuity (BCVA, LogMAR) and total number of needed PRP spots and IVI after 24 months. Results: CMT was significantly higher in G2 compared to G1, initially (p < 0.01) and after 24 months (p = 0.01). CMT was significantly higher in G2b compared to G2a, both initially (p = 0.01) and after 24 months (p < 0.01). BCVA was significantly higher in G1 compared to G2, initially and after 24 months (p = 0.01). BCVA was not significantly different between the two subgroups, initially (p = 0.54) and after 24 months (p = 0.29). The total number of PRP spots was significantly higher in G1 compared to G2 (p < 0.01) but not significantly different between the subgroups (p = 0.8). Conclusion: Regardless of severity of concomitant DME, IVI with sole anti-VEGF or combined with steroids reduced the total number of PRP spots needed within 2 years significantly indicating a favorable effect on activity of PDR. [ABSTRACT FROM AUTHOR]

Purpose: Since non-adherence (NA) to intravitreal therapy with VEGF drugs is one of the most important modifiable factors compromising treatment outcome of nAMD, the purpose of this study was to investigate the contributing factors and barriers during long-term nAMD treatment. Methods: Barriers and potential reasons for NA were prospectively measured using the Adherence Barriers Questionnaire Intravitreal Therapy (ABQ-IVT). A random sample of patients receiving intravitreal therapy was drawn based on data for different treatment periods. Three age-sex matched groups included the treatment periods of ≤ 30 months (group 1), between > 30 months and ≤ 60 months (group 2), and > 60 months (group 3). The occurrence of gaps between treatments and/or OCT visits was evaluated. Results: NA with gaps of > 56 days after the scheduled appointment was detected in 39%, 89%, and 100% of patients in group 1, 2, and 3, respectively (groups 1 and 2 vs group 3, p < 0.001). Two or more of such gaps were observed in 6%, 72%, and 94% of patients in group 1, 2, and 3, respectively. The overall ABQ-IVT score showed corresponding differences between the groups: 25.89 ± 7.68 (group 1, 95% CI 22.07– 29.71), 34.72 ± 10.32 (group 2, 95% CI: 29.59– 38.86), and 33.28 ± 9.04 (group 3, 95% CI 28.78– 37.77). Accordingly, the score was inversely correlated with the number of regular follow-up visits in groups 2 and 3 (Pearson correlation coefficient r = − 0.65 (p = 0.003) and r = − 0.5 (p = 0.034), respectively). Within the groups of longer treatment duration, univariate logistic regression analysis showed higher odds of time commitment and challenge accompanying person to be relevant barriers. Conclusion: NA is an arising problem with increasing duration of intravitreal therapy. Treatment barriers, detected by the ABQ-IVT, might change or increase during the course of the treatment. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is the most common cause of legal blindness in developed countries. Neovascular (ie, wet) AMD is currently managed with intravitreal therapy. Traditional treatments (ie, bevacizumab, ranibizumab, aflibercept) provide high-efficacy therapy but can also require frequent dosing. Newer and future anti-VEGF therapies aim to decrease injection frequency through eitherlonger half life or port-delivery systems (brolucizumab, conbercept, KSI-301, ranibizumab). This review outlines current anti-VEGF treatments and ways by which their duration might be extended. [ABSTRACT FROM AUTHOR]

Visual acuity is a key outcome measure in the treatment of neovascular age-related macular degeneration (nAMD) using anti-vascular endothelial growth factor agents. Large variations in visual responses between individuals within clinical trials and real-world studies may relate to underlying differences in patient and treatment factors. Most notably, a better baseline visual acuity, younger age and smaller choroidal neovascularization lesion size have been strongly associated with achieving better visual outcomes. In addition, there is emerging evidence for other roles including genetic factors and anatomical variables such as fluid status. Apart from patient-related factors, treatments that favor a higher number of injections tend to provide better visual outcomes. Overall, the identification of predictive factors does not currently play an essential role in the clinical management of patients with nAMD. However, they have allowed for the understanding that early detection, timely management and close monitoring of the disease are required to achieve optimal visual outcomes. Further investigation into predictive factors alongside the development of novel therapeutic agents may one day provide a means to accurately predict patient outcomes. Treatment regimens that offer flexible dosing patterns such as the treat-and-extend strategy currently provide a degree of personalization during treatment. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy of intravitreal Aflibercept injection (IAI) for vitrectomized eyes with diabetic macular edema (DME) at one year. Methods: This is a prospective, non-comparative, multicenter observational study including diabetic patients whose HbA1c is < 9%, with visual acuity between 20/400 to 20/40 due to DME, who have undergone vitrectomy since at least 3 months before the first aflibercept injection. Treatment protocol included 5 monthly aflibercept injection followed by a ProReNata regimen during the first year. Visual acuity, OCT findings and number of IAI were assessed at 6 months and one year. Results: Forty-six eyes were included. Indications for vitrectomy were epiretinal membrane (58.7%), intravitreal hemorrhage (26.1%), and vitreomacular traction (8.7%), retinal detachment (4.3%), and other cause (4.3%). Median duration of macular edema was 3 years. Median interval between vitrectomy and first visit was 9 months. Thirty eyes were non-naïve and received previously thermal laser (44.3%), intravitreal injection of triamcinolone (26.7%), of ranibizumab (70%), of dexamethasone implant (36.7%), or bevacizumab (6.7%). Data was available for 35 eyes at 1 year. Visual gain was significant, +6 letters (p < 0.001) and central subfield thickness (CST) decreased significantly (− 108μm, p < 0.001) at 1 year. Mean number of injections was 9.3 and mean interval injection was 5.8 weeks. Conclusion: These results suggest that IAI may be beneficial in vitrectomized eyes with refractory DME which require frequent injections to obtain visual and anatomical improvement. Clinical Trial Registration: http://www.clinicaltrials.gov , registration Number NCT02874859. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the real-life clinical outcome of a single dexamethasone implant (DEX) injection in the treatment of persistent diabetic macular edema (DME) after anti-vascular endothelial growth factor (anti-VEGF) agents in a sample of the Jordanian population. Methods: An observational case study design that involved a retrospective chart review analysis in a tertiary hospital in Amman, Jordan. Patients who showed persistent DME after receiving at least six doses of anti-VEGF agents for DME treatment were included. Results: The study population consisted of 72 participants (29 females, 43 males) having an average age of 66 years. All patients had best-corrected visual acuity (BCVA) less than 0.7 (6/9) and SD-OCT documented center-involved DME. The study results showed that the average baseline BCVA improved from 0.205± 0.1 before DEX injection to 0.358± 0.1 at 3 months post-injection (p< 0.0001). The central mean thickness (CMT) showed significant improvement also (539.347± 132.402 to 379.041± 99.430, p< 0.0001). There was a mean of 3 mmHg increase in intraocular pressure at 3 months post-injection (p< 0.0001), however, only 4% of patients required medical treatment. Other inflammatory biomarkers in OCT, such as intraretinal hyper-reflective dots (HRD), showed significant improvement also (23.67± 16 to 14.83± 13, p< 0.0001). No other significant safety concerns were noticed. Conclusion: A single DEX injection showed significant clinical and anatomical improvement in DME cases that are persistent after anti-VEGF treatment in our sample, with an excellent safety profile. In case of supply shortage of intravitreal injections, which occurs frequently at our center, a single DEX injection may be utilized as an effective DME therapy. Further research is mandated to identify clinical response in a larger sample and more frequent injections. [ABSTRACT FROM AUTHOR]

Submacular hemorrhage (SMH) has been reported to be toxic to the retina based on animal studies. However, observational studies of patients with neovascular-related SMH and those treated with intravitreal anti-vascular growth factor (anti-VEGF) therapy have shown many favorable visual acuity outcomes. We report two cases of neovascular-related SMH with ten or more years of follow-up. The first case was an 83-year old female with a history of nonexudative age-related macular degeneration in both eyes presenting with sudden decrease in vision (20/400) in her right eye due to a large SMH, treated with anti-VEGF therapy. Over the next following months, there was resolution of the hemorrhage and return of good visual acuity. At 10-year follow-up, visual acuity was 20/30 in the right eye. The second case was a 49-year old female with a history of presumed ocular histoplasmosis syndrome (POHS), presenting with sudden vision loss (20/400) in her right eye due to large, thick SMH. With observation and intermittent anti-VEGF therapy, there was resolution of the hemorrhage. At 30-year follow-up, visual acuity was 20/20 in the right eye. [ABSTRACT FROM AUTHOR]

Purpose: Since the beginning of the COVID-19 pandemic, news related to the pandemic has created a feeling of fear, particularly among high-risk groups including elderly patients. This study aimed to assess the fear associated with COVID-19 and to evaluate the fear of vision decrease related to the delay of treatment in neovascular age-related macular degeneration patients (nAMD) during the pandemic. Patients and Methods: This is a prospective cross-sectional study of 160 actively treated patients with nAMD enrolled between September and November 2020 at a tertiary hospital in Québec, Canada. For each participant, demographic and clinical data were collected. The anxiety was rated in a questionnaire composed of two sections: the Fear of COVID-19 Scale (FCV-19S) and eight additional questions to assess ophthalmology-related COVID-19 statements. Results: The mean ± standard deviation level of FCV-19S was 17.05± 4.38. In the multivariable analysis, it was significantly higher in women (p< 0.001) and lower in patients with a high school education vs elementary school (p=0.009). In the ophthalmology-related statements, 16% feared vision loss because of difficulties in maintaining regular follow-ups during the pandemic. The female gender was significantly associated with a higher tendency to postpone their appointment (p=0.03). No association was found between the patients' underlying disease characteristics and higher fear of vision loss. Conclusion: Despite the massive impact of the pandemic, anxiety related to COVID-19 and delaying ophthalmology treatments remained relatively low in nAMD patients. Greater explanations to address this fear may reduce anxiety level, especially among female patients and those with an elementary school education. [ABSTRACT FROM AUTHOR]

Purpose: This meta-analysis aims to summarize 12-month best-corrected visual acuity (BCVA) outcomes in response to anti-vascular endothelial growth factor (VEGF) therapy and dexamethasone implant for the treatment of diabetic macular edema (DME) and to identify factors affecting treatment response using evidence generated from meta-regression. Methods: A systematic review of electronic databases was conducted to identify randomized controlled trials (RCTs) and real-life/observational studies that reported 12-month changes in BCVA in patients with DME on anti-VEGF or dexamethasone implant treatment in monotherapy. Study factors that were analyzed are baseline patient characteristics, study type, drug employed, number of injections and 12-month change in BCVA. Data were pooled in a random-effects meta-analysis with BCVA change as the main outcome. Meta-regression was conducted to assess the impact of multiple covariates. Results: One-hundred-five heterogeneous study populations (45,032 eyes) were identified and included in the analysis. The use of anti-VEGFs and dexamethasone implant induced an overall increase of +8.13 ETDRS letters in BCVA at 12 months of follow-up. Meta-regression provided evidence that mean BCVA change using anti-VEGFs was not statistically higher for RCTs (p=0.35) compared to observational studies. Dexamethasone implant showed a trend for better results in observational studies over RCTs. Populations following a fixed aflibercept regimen performed better than those following a reactive treatment regimen. Mean BCVA gain was higher in younger populations (p< 0.001), with lower baseline BCVA (p< 0.0001) and longer diabetes duration (p< 0.0001), receiving a higher number of injections (p< 0.0001). Conclusion: Intravitreal therapy with anti-VEGFs or dexamethasone implant produces a significant improvement in BCVA at 12 months in patients with DME. Meta-regression identified the modifiable covariates that can be targeted in order to maximize functional results. [ABSTRACT FROM AUTHOR]

Background: The Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale (DRSS) is a standard approach to measure diabetic retinopathy (DR) severity. Many clinical trials evaluating drug intervention for DR rely upon demonstration of a therapeutic effect through measurement of a 2- or 3-step improvement or progression on the DRSS; however, these binary endpoints require a relatively large sample size for a reliable estimate of therapeutic efficacy, especially when the SOC (eg, anti-VEGF) is used as a control. This study was designed to evaluate the sensitivity and statistical efficiency of detecting a drug effect in DR across different DRSS endpoints, and present alternative analytical approaches to enable smaller-size DR trials for detecting a reliable efficacy signal before moving into larger confirmatory DR trials. Methods: Data from two randomized, double-blinded, controlled Phase III trials, that enrolled patients with decreased vision due to center-involved DME and the presence of macular edema documented on optical coherence tomography and simulated data, were used for this study. Changes in DRSS steps during a 3-month period from patients (n=205) with no active intervention were used to confirm the reliability of DRSS outcomes. A simulation study compared sensitivity and statistical efficiency across different DRSS endpoints. Results: The standard deviation of step change between baseline and month 3 DRSS across different steps at baseline were all within 1 step, confirming the reliability of DRSS measure by each step. Efficiency of detecting reliable therapeutic efficacy was augmented when treatment effect in improvement and progression was evaluated together; highest sensitivity was observed when change in DRSS steps was used directly as an endpoint. Conclusion: DRSS step change may provide more robust sensitivity and statistical efficiency. It is therefore a more cost-effective endpoint for the detection of therapeutic efficacy signal in drug discoveries in DR. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluates the effect of anti-vascular endothelial growth factor (anti-VEGF) therapy on microaneurysm changes and foveal avascular zone (FAZ) using optical coherence tomography angiography (OCTA) in patients with diabetic macular edema (DME). Design: Prospective observational study. Materials and Methods: This study involved patients with DME undergoing anti-VEGF treatment (aflibercept, ranibizumab, and bevacizumab). Macula OCTA images were obtained before (visit 0) and 1 month after (visit 1) anti-VEGF injection. Microaneurysm counts were performed, and the FAZ was evaluated in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). The differences in microaneurysms, FAZ, and clinical correlations were analyzed. Results: A total of 152 eyes were analyzed. The patients' mean age was 59 years. Bevacizumab was used in 69.7%, ranibizumab in 15.1%, and aflibercept in 15.1%. There was a significant reduction in the FAZ in the SCP and DCP between visits 0 and 1. All anti-VEGF medications reduced the number of microaneurysms (p< 0.01). After treatment, changes in the FAZ in SCP and DCP corresponded with changes in visual acuity (p< 0.01). Conclusion: Microaneurysms as detected by OCTA might serve as a biomarker for a clinical response to anti-VEGF treatment in the short term. The FAZ might also predict visual acuity improvement after anti-VEGF injection. Trial Registration: Thai Clinical Trials Registry (TCTR20161010005). [ABSTRACT FROM AUTHOR]

Purpose: To report trends in real-world outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) in the United Kingdom (UK) over the last decade. Design: Systematic review. Methods: Medline, PubMed, and Embase databases were searched from 9 April 2010 to 8 April 2020 for publications that met the inclusion criteria: treatment-naïve eyes, UK-only data and ≥ 1 year of follow-up. ICHOM (International Consortium for Health Outcome Measures) outcomes and study quality were assessed. Visual acuity (VA) trends were assessed in studies with ≥ 100 eyes at baseline. Results: Twenty-six studies (n=25,761 eyes) were included, meeting 14– 17 out of 20 Institute of Health Economics Quality Appraisal of Case Series checklist domains. Only ranibizumab and aflibercept outcome data were available. The mean injection number in the first year of treatment was 5.9 in publications from 2010 to 2015 and 7.1 from 2015 to 2020. Average baseline VA and mean one-year, two-year and three-year VA gains gradually improved over the last decade. Longer-term studies reported that the visual gains achieved in the first year of treatment were rarely maintained, with under-treatment a likely contributing factor. Conclusion: UK real-world outcomes have improved over the last decade with improved service delivery and the adoption of more proactive treatment regimens but are still not always as impressive as registration clinical trial results. Access to longer-acting anti-VEGF therapies would reduce the treatment burden for patients, carers, and the healthcare system, potentially making replication of clinical trial results possible in the NHS. [ABSTRACT FROM AUTHOR]

Background: Diabetic retinopathy (DR) may be asymptomatic in both mild and advanced stages. A patient's accurate perception of their DR severity may therefore be critical for effective self-management behaviors and understanding the need for timely intervention and follow-up. Purpose: To evaluate the relationship between self-reported and actual retinopathy severity in diabetic patients. Methods: This study was a single-center cross-sectional survey. Diabetic patients identified by enterprise data warehouse were sent an online questionnaire where they were asked to self-assess for presence of DR and grade their severity. Actual DR grading was determined via chart review. The primary outcome measures were patient-assessed DR severity and agreement with actual DR severity. Results: Of 3208 invitations sent, 324 (10%) patients responded and 319 responses were analyzed. The data showed that 39 of 253 (15%) with no DR, 26 of 40 (65%) with mild/moderate DR, and 24 of 26 (92%) with severe DR believed they had DR (p< 0.001). Of those with no DR, 214 of 253 (85%) accurately assessed absence of DR. Of those with mild/moderate DR, 25 of 40 (63%) accurately assessed their severity, 14 of 40 (35%) believed they had no DR, and 1 of 40 (3%) believed they had severe DR. In patients with severe DR, 9 of 26 (35%) correctly assessed their severity, 15 of 26 (58%) believed they had mild/moderate DR, and 2 of 26 (8%) believed they had no DR. Conclusion: Patients with severe DR were the most likely to report presence of DR, but often underestimated their disease severity. Many with mild/moderate DR did not realize they had DR. This consistent underestimation of severity across all a significant barrier to timely follow-up and treatment necessary to prevent future visual impairment. [ABSTRACT FROM AUTHOR]

Purpose: There are limited published data regarding the use of supplemental intravitreal therapies in patients with diabetic macular edema (DME) following treatment with the 0.19 mg fluocinolone acetonide (FAc; ILUVIEN®) intravitreal implant. The aim of this report was to analyze five challenging eyes that required supplemental therapies after treatment with the FAc implant. Methods: This is a retrospective case series conducted at the Centro Hospitalar Universitário do Porto in Porto, Portugal, between 2015 and 2019. It aimed to assess the patient background, treatment history and patient outcomes in challenging clinical cases in which intravitreal injections (IVI) of ranibizumab had been given pro re nata following treatment with the FAc implant (with a minimum follow-up of 33 months). Parameters measured included best-corrected visual acuity in early treatment diabetic retinopathy scale, central macular thickness and intraocular pressure. Patients: Five eyes (three patients) diagnosed with persistent or recurrent DME and suitable for treatment with the FAc implant according to its licensed indication in Europe. Results: In the first 2 patients, one bilateral, DME was refractory to IVI of short-acting corticosteroids and anti-VEGF. Following FAc therapy, there was a favorable evolution and a clear regression of diabetic retinopathy (DR) severity. Supplemental treatments were adopted, but a reduced number of treatments were needed beyond three years in these cases. The third case had bilateral DME. One eye had been vitrectomized and FAc therapy led to resolution of DME within 6 months. In the contralateral eye, the control of DME was dependent on anti-VEGF supplemental treatments until a pars plana vitrectomy was performed. Conclusion: The multifactorial nature of DME means there is a need for an individualized treatment approach to the management of DME. It also explains why some patients need a combined or a more aggressive approach to therapy in order to achieve successful outcomes for the patient. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the predictors of early diabetic retinopathy (DR) improvement in the RIDE/RISE (NCT00473382/NCT00473330) clinical trials. Patients and Methods: In RIDE/RISE, adult patients with vision loss due to diabetic macular edema (DME) were randomized to monthly intravitreal ranibizumab 0.3 or 0.5 mg (n=502 total) or sham (n=257). DR severity was graded (using the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale). In this post hoc analysis of RIDE/RISE, eyes with baseline DR score ≥ 35 were evaluated for ≥ 2-step improvements, and eyes with baseline DR score ≥ 43 were evaluated for ≥ 3-step improvements. The characteristics associated with ≥ 2- or ≥ 3-step DR improvement at months 3 or 6 were assessed using univariate and/or multivariable analyses. Results: The percentage of eyes with a ≥ 2- or ≥ 3-step DR improvement was 20.1% and 3.7% at month 3 and 31.2% and 5.8% at month 6. Odds of ≥ 2-step DR improvement at months 3 or 6 were significantly greater in eyes with moderately severe to severe nonproliferative DR (NPDR) at baseline versus less severe or more severe DR (both P< 0.0001). At month 6, odds of ≥ 2-step DR improvement were significantly greater in eyes with no DME at month 3 (P=0.008). Most patients with ≥ 3-step DR improvement at months 3 or 6 had proliferative DR (PDR) at baseline (83.3% and 66.7%). Conclusion: The strongest predictors of DR response to ranibizumab at month 6 were baseline DR severity and DME quiescence at month 3. Eyes with the most robust early improvements had moderately severe or severe NPDR or PDR at baseline. [ABSTRACT FROM AUTHOR]

Purpose: To report a case series of initial responses to intravitreal brolucizumab in patients already undergoing anti-VEGF therapy for wet age-related macular degeneration. Case Series: Six eyes (6 patients) with a history of wet age-related macular degeneration presented with either decline in vision or no improvement while undergoing treatment with anti-VEGF therapy – aflibercept or bevacizumab. Patients were switched to intravitreal brolucizumab. Four weeks post-injection, there was no significant change in visual acuity. Optical coherence tomography scans were taken and improved IRF/SRF, central macular thickness and average pericentral thickness were observed in all 6 patients. No serious adverse reactions were observed, including signs of vasculitis or increase in anterior chamber cell count at the 4-week follow-up for all 6 patients. Conclusion: Intravitreal brolucizumab appears to be a safe and limitedly effective option for patients with recalcitrant CNV from wet AMD. [ABSTRACT FROM AUTHOR]

Purpose: The non-interventional OCEAN study (NCT02194803) evaluated frequency and monitoring of ranibizumab injections for retinal vein occlusion (RVO) in routine practice in Germany. Methods: RVO patients (including branch and central RVO (BRVO/CRVO)) receiving ranibizumab were included. Best-corrected visual acuity (BCVA) testing, imaging and treatment were performed at the investigators' discretion and documented over 24 months. Results: Overall, 744 RVO patients (27% BRVO, 16% CRVO, remaining unspecified RVO) were included. For 74% of patients, data were available for the 12-month visit and for 56% for the 24-month visit. Mean baseline BCVA was 52.0 Early Treatment for Diabetic Retinopathy Study (ETDRS) letters (BRVO: 55.9, CRVO: 43.9). BCVA improved rapidly within the first 3 months, reaching 64.3 letters at 12 months and 64.7 at 24 months. CRVO patients showed less improvement than those with BRVO. Patients received a median of 4 (5) injections over 12 (24) months, with 100% of patients receiving injections at baseline, 70% at Month 1 and 81% at Month 2. Overall, 40% of patients demonstrated a ≥15 letter increase within the first 3 months (42% BRVO, 46% CRVO). Patients with low initial BCVA (<50 letters) showed greater improvement than patients with higher baseline BCVA. Due to considerable loss to follow-up, the number of injections and optical coherence tomography (OCT) examinations were not associated with the change in BCVA. Conclusion: Patients with RVO in routine practice in Germany received fewer injections and fewer OCT examinations than in clinical trials. CRVO patients showed less and later improvement compared to BRVO patients. [ABSTRACT FROM AUTHOR]

Aim: The incidence and prevalence of diabetes mellitus (DM) in Australia is increasing. Thus, it is essential that practitioners appreciate the impending effect that increasing incidence of diabetes has on patients and the wider community. Accordingly, this study examines the humanistic burden of intravitreal injections for the treatment of diabetic macular oedema (DMO) among several health variables. Methods: Survey data from a representative sample of Australian adults undergoing treatment for DMO were examined. Respondents participated via an online survey recruited by means of a national online consumer panel and the New South Wales and Victorian Diabetes Foundations. The online survey included questions relating to the humanistic burden of disease, such as the emotional and physical impact of intravitreal injection therapy; the practical impacts of injection therapy; and to identify potential improvements to treatment regimens. Results: Sixty-five participants took part in the online survey. Of these, 49% had their most recent injection <1 month prior to completing the survey. The mean age was 52.5 years, with the majority of patients in full-time work. A substantial proportion of participants had several comorbidities, with a significantly high Charlson comorbidity index of 2.7. Participants reported the main burden of DMO care was the direct cost of medical treatment and the time burden demanded upon their carers. Results suggest that the overall burden is significant for those with diabetes and increases as additional complications of diabetes occur. Conclusion: These results suggest that treatment strategies for DMO should consider clinical, humanistic and economic burden and patients should be educated on the roles of complications in disease outcomes. Less frequent treatment regimens could also reduce the economic burden and assist in decreasing the effect on health care resources, relevant to the escalation in the prevalence of diabetes. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity (ROP) is a leading and preventable cause of childhood blindness worldwide. Although laser photocoagulation remains the gold standard for treatment, the off-label use of anti-vascular endothelial growth factor (anti-VEGF) therapy to treat ROP, particularly posterior zone I disease, is increasing. Although initial studies on anti-VEGF therapy for ROP have focused on bevacizumab, recent studies have proposed that ranibizumab may be a safer and more effective alternative for use in this population. This review updates recent evidence regarding the use of ranibizumab in the management of ROP. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate long-term structural and functional changes that happen to the optic nerve and retina following ranibizumab (Lucentis) injections in diabetic macular edema (DME) patients. Methods: Patients with clinically significant DME requiring anti-VEGF injections underwent pre-injection baseline, 6, 12, and 24 month follow-up tests. The tests performed were optical coherence tomography (OCT), best-corrected visual acuity (BCVA), and visual field (VF). Wide-field fluorescein angiogram (IVFA) was performed to monitor the progression of diabetic ischemia. Results: A total of 30 patients requiring anti-VEGF injections and 21 control patients not requiring anti-VEGF injections were enrolled in the study. From baseline, the average macular thickness significantly decreased (p<0.0002) over the 24-month time period. Mean perfused ratio significantly increased (p<0.0005) at 6, 12, and 24 months. Cup volume and vertical cup-to-disk ratio significantly increased (p<0.0014) over the study period. This was verified by masked independent grading of patient optic nerve stereo-photographs by glaucoma specialists. BCVA significantly (p<0.0006) improved over the study period. VFs showed a non-significant trend of deteriorating peripheral vision at 12 and 24 months. Conclusion: Clinically, anti-VEGF therapy appears to affect the optic nerve by increasing cup volume and increasing vertical cup/disk ratio over time. The results provide a cautionary note to monitor both the retina and optic nerve status in patients undergoing frequent injections. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the safety of different concentrations of anti-VEGF on retinal cells. Methods: Non-diabetic and streptozotocin (STZ)-induced diabetic rats received intravitreal rat anti-VEGF injections that had final vitreous concentrations of 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL. Rats were also injected with the clinical dose of ranibizumab. TUNEL assay was performed on sectioned eyes to evaluate apoptotic cells. In vitro, rat retinal cell cultures were exposed to 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL of ranibizumab for 48 and 72 hrs. Cellular metabolic activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, necrosis by lactate dehydrogenase (LDH), and apoptosis by cell death enzyme-linked immunosorbent assay (ELISA). Results: Diabetic rats had a significant increase (p<0.03) in apoptotic cell death at half the clinical dose, at the clinical dose, and at double the clinical dose. In vitro, MTT showed a significant decrease (p<0.04) in cellular metabolic activity at the clinical dose and double the clinical dose compared to control at 48 and 72 hrs. LDH showed a significant increase (p<0.04) in necrosis at the clinical dose and double the clinical dose compared to control at 48 and 72 hrs. ELISA showed a significant increase (p<0.04) in apoptosis at half the clinical dose, at the clinical dose, and double the clinical dose, compared to control at 48 and 72 hrs. Conclusions: Anti-VEGF treatment may be potentially detrimental to the retina by decreasing cellular metabolic activity and increasing cytotoxicity of retinal cells. The results provide a cautionary note to monitor both the retina and optic nerve status in patients undergoing frequent injections. [ABSTRACT FROM AUTHOR]

Purpose: To determine the early effects of intravitreal anti-VEGF and dexamethasone application on blood flow velocities in patients with retinal vein occlusions.Methods: The ophthalmic (OA) and the central retinal arteries (CRAs) of the affected and unaffected eyes of 21 patients with central retinal vein occlusion (CRVO), and 26 patients with branch retinal vein occlusion (BRVO) were investigated by Color Doppler imaging (CDI). Peak systolic volume (PSV), end diastolic volume (EDV), and average blood velocity (Vmean) of the CRA and OA were measured and resistive indexes (RI) were calculated at pre-injection and the 1st week and 1st month post-injection.Results: There was no statistically significant difference between the OA values for affected and unaffected eyes in the CRVO group before treatment. The CRA, EDV, and Vmean values were significantly lower in affected eyes. Blood flow velocities of both CRA and OA were not significantly different than in the fellow unaffected eyes in the BRVO group. The differences between PSV, EDV, and Vmean measurements of OA and CRA at different times pre- and post-injection in response to anti-VEGF and dexamethasone treatment in the CRVO group were significant; but there was no difference in RI value. OA blood flow velocity measurements were not statistically different post-injection in the BRVO group; however, the values of PSV and EDV of CRA decreased post-injection.Conclusion: Intravitreal anti-VEGF and dexamethasone implant may induce retinal arteriolar vasoconstriction in patients with retinal vein occlusion. [ABSTRACT FROM AUTHOR]

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) medications play an increasingly critical role in numerous retinal vascular diseases. Initially, anti-VEGF medications came in vials that had to be drawn up by the physician into a syringe for administration. In 2018, the US Food and Drug Administration (US FDA) approved the ranibizumab 0.3 mg prefilled syringe (PFS), and in October 2016, the US FDA approved the ranibizumab 0.5 mg PFS. This article discusses the advantages of the PFS, including reduced injection time, possible reduced risk of endophthalmitis, reduction in intraocular air bubbles and silicone oil droplets, and improved precision in the volume and dose of intravitreal ranibizumab administered, along with possible disadvantages. Implications of the innovation of the PFS on intravitreal injection technique and clinical practice pattern are discussed and reviewed. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the use of aflibercept, triamcinolone acetonide, and photodynamic therapy (PDT) in the treatment of avascular pigment epithelium detachments (aPEDs). Patients and methods: Patients with treatment-naïve aPEDs ≥1,500 µm in diameter were randomized to treatment or observation. Treatment consisted of 6 monthly intravitreal injections of aflibercept. If the aPED persisted, the patients were treated with half-fluence PDT in combination with intravitreal triamcinolone acetonide and aflibercept. The primary outcome was change of best-corrected visual acuity (BCVA) after 24 months of follow-up. Secondary outcomes were changes in pigment epithelium volume, height and diameter, central retinal thickness, and number of patients developing choroidal neovascularization or geographic atrophy (GA). Results: Treatment and inclusion of patients were stopped after an interim analysis of 6-month data because 75% of the aPEDs were in different stages of GA. Nine patients with aPED were included in the study, of these one patient was excluded because of bilateral central serous chorioretinopathy. The remaining eight had drusenoid aPEDs. After 24 months of follow-up, estimated means of BCVA decreased by 4.2 and 20.8 letters in the treatment and observation group, respectively. This decrease over time was not significantly different between groups (P=0.140, 95% CI -5.3, 38.6). Estimated means of PED volume, height, diameter, and central retinal thickness were not significantly different between groups. Choroidal neovascularization and retinal pigment epithelium tear developed in one patient in the treatment group. One patient in the treatment group and two patients in the observation group progressed to complete retinal pigment epithelium and outer retinal atrophy. A decrease in PED volume was associated with the development of complete retinal pigment epithelium and outer retinal atrophy (P=0.029). Conclusion: This small trial indicates that multitargeted, primarily antiangiogenic therapy does not favorably alter the natural course of drusenoid aPEDs. [ABSTRACT FROM AUTHOR]

Purpose: To quantify the burden and quality of life of patients and their caregivers in a cohort of patients with neovascular age-related macular degeneration (nAMD) in an Australian clinical setting. Methods: A total of 103 patients undergoing anti-vascular endothelial growth factor (VEGF) therapy for nAMD were asked to complete questionnaires relating to the financial and time burdens of nAMD. Results: All patients completed the questionnaires. Loss in productivity due to attendance of appointments was 4.4±1.7 hours per month, with additional time lost by caregivers. Financial strain was incurred by direct medical costs associated with intravitreal assessment and injections at an average of AU$199.2±$83.1 per month. Indirect costs incurred averaged $64.8±$79.7 per month. Qualitative indirect costs due to loss of productivity for the patient, unpaid caregivers, and loss of productivity due to premature mortality were also a considerable burden. Overall mean Visual Function Questionnaire and EuroQol 5D-3L scores were correlated with visual acuity and demonstrated patients' subjective decline in quality of vision. Conclusion: Management of nAMD carries a substantial burden on patients and caregivers. These results provide important information in understanding the effect of anti-VEGF therapy among patients with nAMD. Together with the quality-of-life burden on the patients, the management of nAMD has a significant societal impact. [ABSTRACT FROM AUTHOR]

Purpose: The objective of the study was to assess the effect of off-label photodynamic therapy (PDT) in combination with intravitreal off-label ziv-aflibercept or off-label aflibercept injection in patients with chronic or repeatedly recurrent acute central serous chorioretinopathy (CSC).Patients and methods: Changes in best corrected visual acuity (BCVA) and subfoveal subretinal fluid (sSRF) and maximum subretinal fluid (mSRF) were retrospectively analyzed in a single-center cohort study of 17 patients (18 eyes) with persistent subretinal fluid for more than 3 months of duration of CSC. Treatment efficacy was measured between injection and PDT at 30±15 days, 90±15 days and 180±30 days after PDT.Results: Significant reduction of sSRF and mSRF was shown after therapy with ziv-aflibercept and aflibercept combined with PDT (p<0.001). Course of BCVA showed non-significant improvement within 6 months (p=0.065). One case of allergic reaction after fluorescein angiography and one case of ophthalmic migraine after ziv-aflibercept injection were documented. One case of reversible vision loss occurred during 6 months after combination therapy. No other adverse events or side effects were reported.Conclusion: Combination therapy of ziv-aflibercept and aflibercept with PDT seems to be beneficial, even in cases of chronic or repeatedly recurrent acute CSC. This includes cases of CSC resistant to or recurrent after medical treatment, PDT alone or therapy with anti-vascular endothelial growth factor alone. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate changes in contrast sensitivity (CS), visual acuity (VA), central retinal thickness (CRT), and vision-related quality of life in subjects with recalcitrant diabetic macular edema switched from long-term ranibizumab treatment to aflibercept. Patients and methods: In this prospective, investigator-masked, single-center study, 40 patients with persistent fluid, despite previous ranibizumab treatment, were switched to aflibercept with 5 consecutive monthly doses. The primary outcome was mean change from baseline to week 20 in Pelli-Robson CS. Secondary outcomes were mean change from baseline in best-corrected VA (BCVA), CRT, and National Eye Institute 25-Item Visual Function Questionnaire score. Results: Fifty eyes (baseline VA >6/30) were evaluated. A median of 21.1±11.9 (range 5-55) ranibizumab injections were administered prior to initiation of aflibercept. Mean CS improved from 1.40±0.14 log units at baseline to 1.46±0.15 log units at week 20 (P<0.001). VA improved with mean logarithm of the minimum angle of resolution BCVA of 0.33±0.19 at baseline compared with logarithm of the minimum angle of resolution BCVA of 0.28±0.16 at week 20 (P=0.0016). Mean CRT decreased from 324±85 to 289±61 µm (P<0.001). Twenty-two (55%) patients experienced an overall improvement in National Eye Institute 25-Item Visual Function Questionnaire score. Interestingly, an association was found between changes in CS and change in CRT (r²=0.385, P<0.001) and between changes in BCVA and change in CRT (r²=0.092, P=0.032). Conclusion: Switching from ranibizumab to aflibercept in patients with recalcitrant diabetic macular edema resulted in an improvement in all measured metrics, including CS, VA, and CRT. A majority of patients also indicated an improvement in vision-related quality of life. The finding of a stronger relationship between changes in CRT and CS compared with changes in CRT and BCVA suggests that the inclusion of CS as an endpoint may yield a more complete understanding of visual outcomes than that obtained by using VA alone. [ABSTRACT FROM AUTHOR]

Purpose: To study vitreoretinal interface (VRI) abnormalities in diabetic macular edema (DME) and the influence of these on the effectiveness of intravitreal anti-vascular endothelial growth factor (VEGF) therapy. Methods: VRI status and central retinal thickness (CRT) were evaluated using line and 3D-reference scans obtained using spectral domain-optical coherence tomography RTVue-100 before and 1 month after intravitreal anti-VEGF injection (IVI). VRI status was categorized into five subgroups: normal VRI, retinal surface wrinkling associated with the eccentric epiretinal membrane (ERM), ERM involving the macular center, vitreomacular adhesion (VMA), and vitreomacular traction (VMT). Results: A total of 105 eyes of 89 patients were included in the study. One month after IVI, the mean change of CRT in normal VRI eyes and eyes with VRI abnormalities was -128.0±144.7 μm and -53.0±96.4 μm (p<0.05), respectively. The mean change of CRT 1 month after IVI in each subgroup with VRI abnormalities, apart from the subgroup with retinal wrinkling associated with eccentric ERM, was statistically significantly lower compared to the eyes with normal VRI (p<0.05). Conclusion: VRI abnormalities significantly reduce the effectiveness of intravitreal anti-VEGF therapy in eyes with DME. Eyes with noticeable changes of VRI, including ERM involving the macular center, VMA, and VMT have a poorer response to anti-VEGF therapy compared to eyes with normal VRI or eccentric ERM. [ABSTRACT FROM AUTHOR]