Efficacy and safety of a new ranibizumab biosimilar CKD-701 using a pro re nata treatment regimen in neovascular age-related macular degeneration: A phase 3 randomized clinical trial.
PLoS One. 2022 Nov 14
Yoon CK, Oh J, Bae K, Park UC, Yu KS, Yu HG.
Purpose: This study aimed to establish the efficacy, safety, and immunogenicity equivalence of the proposed biosimilar CKD-701 with the reference ranibizumab in patients with treatment-naïve neovascular age-related macular degeneration (nAMD).
Patients and methods: A total of 312 participants with active subfoveal choroidal neovascularization were randomly assigned to either the CKD-701 (n = 156) or reference ranibizumab (n = 156) arms. The initial 3-month loading intraocular injections were followed by pro re nata (PRN) dosing for 9 months. The primary outcome was the proportion of patients with less than 15-letters of corrected visual acuity (BCVA) loss at 3 months visit (one month after last loading injection) compared to the baseline time point. The presence of retinal fluid, and changes in BCVA and central retinal thickness (CRT) were assessed as secondary efficacy outcomes. Immunogenicity and safety were evaluated in both treatment arms.
Results: In the CKD-701 arm, 143 (97.95%) patients lost <15 letters in the BCVA at 3 months compared to 143 (98.62%) in the reference arm (P = 0.67). The BCVA improved with a mean improvement of +7.0 (CKD-701) and +6.2 (ranibizumab) letters at 3 months (P = 0.43). The least-squares mean (SE) changes in CRT at 3 months from the baseline were -119.3 (12.0) μm and -124.5 (11.9) μm in the CKD-701 and ranibizumab groups, respectively (P = 0.74). The proportion of participants with subretinal or intraretinal fluid at 3, 6, and 12 months was similar between the study arms. The number (SE) of injections were 8.36 (3.13) in the CKD-701 and 8.26 (2.92) in ranibizumab (P = 0.62). The occurrence of adverse events and antidrug antibody in the study arms were also not statistically different.
Conclusion: CKD-701 is a biosimilar to the reference ranibizumab in terms of efficacy, safety, and immunogenicity for the treatment of patients with nAMD. Moreover, improvement and maintenance of visual outcome were achieved through PRN regimen.
Final 4-year results of the RAINBOW real-world study: intravitreal aflibercept dosing regimens in France in treatment-naïve patients with neovascular age-related macular degeneration.
Graefes Archive for Clinical and Experimental Ophthalmology. 2022 Nov 18
Cohen SY, Dominguez M, Coscas F, Faure C, Baillif S, Oubraham H, Kodjikian L, Weber M, RAINBOW study investigators.
Purpose: The purpose of this study is to evaluate real-world treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) in routine clinical practice in France.
Methods: RAINBOW (NCT02279537) was an ambispective, observational, 4-year study assessing IVT-AFL effectiveness, treatment patterns, and safety in patients with nAMD in France. Treatment-naïve patients prescribed IVT-AFL and treated according to local practice (pro re nata or treat-and-extend) were eligible. Three treatment cohorts were retrospectively identified based on their treatment pattern within the first 12 months: regular (3 initial monthly IVT-AFL injections received within 45-90 days after the first injection in month 0 and followed by injections every 2 months), irregular with the initial monthly injections, and irregular without the initial monthly injections. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline to month 12. The 48-month results are described here.
Results: Overall, the study included 516 patients (each with one study eye), and 30.2% of patients completed 48 months of IVT-AFL treatment. Mean change in BCVA from baseline (56.5 letters) to month 48 for patients with an assessment at both time points was + 1.1 (regular cohort, n = 47), + 0.1 (irregular cohort with initial monthly injections, n = 115), and - 1.3 letters (irregular cohort without initial monthly injections, n = 26), representing a decrease from the gains achieved at month 12. Mean number of IVT-AFL injections received by month 48 in the treatment cohorts was 14.9, 13.7, and 11.9, respectively. The safety profile of IVT-AFL was consistent with previous studies.
Conclusion: In RAINBOW, the 48-month results demonstrate a lack of long-term effectiveness of IVT-AFL treatment of nAMD due to progressive undertreatment in routine clinical practice in France. These real-world findings highlight the importance of 3 initial monthly IVT-AFL injections followed by continuous proactive treatment beyond the first year to achieve optimal functional outcomes.
RISK OF DISEASE
Glaucoma progression in patients receiving intravitreal anti-VEGF treatment for neovascular age-related macular degeneration.
Acta Ophthalmologica. 2022 Nov 17
Pirinen I, Leinonen S, Helminen M, Hujanen P, Vaajanen A, Tuulonen A, Uusitalo-Järvinen H.
Purpose: The purpose of this study was to investigate how often glaucoma and neovascular age-related macular degeneration (nAMD) occur in the same patient and to evaluate whether glaucoma progression is faster in eyes treated with intravitreal anti-VEGF medications for nAMD.
Methods: This single-centre retrospective real-world data (RWD) consists of medical records of 6314 glaucoma and 2166 nAMD patients treated in 2008-2017 in Tays Eye Centre, Finland. To study glaucoma progression, changes in visual fields (mean deviation [MD], dB/year), IOP (mmHg/year) and fundus photographs (progression, yes/no) were compared in glaucoma eyes with and without anti-VEGF treatment for nAMD and ≥1 year follow-up.
Results: During the 10-year period, 147 patients with glaucoma received intravitreal anti-VEGF treatment for nAMD corresponding to 2% of glaucoma and 7% of nAMD patients. The mean change in MD was -0.70 dB/year (SD 1.8) vs. -0.27 dB/year (SD 1.7) (p = 0.027) in glaucoma eyes with (n = 37) and without (n = 4304) anti-VEGF injections, respectively. In patients with bilateral glaucoma and unilateral nAMD treated with anti-VEGF injections (n = 20), MD declined at -0.62 dB/year (SD 1.9) vs 0.33 dB/year (SD 1.5) (p = 0.654), and glaucoma progression was detected in 14/20 vs 10/20 (p = 0.219) fundus photographs in eyes with anti-VEGF treatment compared with their untreated fellow eyes.
Conclusion: nAMD and glaucoma were found co-existing in the same eye at rates that were similar to the age-corrected prevalence of the two diseases in the general population. Our results suggest that intravitreal anti-VEGF treatment for nAMD may accelerate glaucoma progression.
Role of anti-vascular endothelial growth factor in the management of non-proliferative diabetic retinopathy without centre-involving diabetic macular oedema: a meta-analysis of trials.
Eye (London, England). 2022 Nov 11.
Chaudhary V, Sarohia GS, Phillips MR, Park D, Xie J, Zeraatkar D, Fung M, Thabane L, Loewenstein A, Holz FG, Garg SJ, Kaiser PK, Bhandari M, Guymer RH, Fraser-Bell S, Sivaprasad S, Wykoff CC.
This systematic review and meta-analysis investigated the impact of anti-vascular endothelial growth factor (VEGF) treatment in management of eyes with non-proliferative diabetic retinopathy (NPDR) without centre involving diabetic macular oedema (CI-DMO). We searched multiple databases for all randomised clinical trials (RCTs) that evaluated anti-VEGF treatment versus observation in eyes with NPDR without CI-DMO. Data was collected for six outcomes (best corrected visual acuity (BCVA) improvement, diabetic retinopathy severity score (DRSS), central subfield thickness, progression to vision threatening complications (VTCs), ocular adverse events and quality of life measures). Risk of bias was assessed using Cochrane risk-of-bias tool for randomised trials (RoB 2) and certainty of evidence was assessed using Grade of Recommendations, Assessment, Development and Evaluation (GRADE). We identified a total of 2 unique RCTs that compared aflibercept and sham to treat a total of 811 eyes. For BCVA change, there was a small, clinically insignificant benefit for aflibercept treatment at year 2 (MD 0.70, 95% CI 0.02-1.38, GRADE rating: MODERATE). DRSS demonstrated a statistically significant improvement with aflibercept use at year 2 (RR 3.76, 95% CI 2.75-5.13, GRADE rating: MODERATE). VTCs were significantly less in aflibercept arm at year 2 (RR 0.30, 95% CI 0.23-0.40, GRADE rating: MODERATE). In conclusion, aflibercept treatment versus observation in eyes with NPDR without CI-DMO can result in reduced risk of development of VTCs and regression of DRSS score over 2 years. Future trials are needed to increase the precision of the treatment effect and to provide data on quality-of-life metrics.PROSPERO Registration: CRD42021288608.
Risk of subsequent dementia or Alzheimer’s disease among patients with age-related macular degeneration: A systematic review and meta-analysis.
American Journal of Ophthalmology 2022 Nov 11
Tsai HR, Lo RY, Liang KH, Chen TL, Huang HK, Wang JH, Lee YC.
Purpose: Alzheimer’s disease (AD), a common form of dementia, shares several clinical and pathological features with age-related macular degeneration (AMD). Epidemiological reports on the association of AMD with subsequent dementia or AD are inconsistent.
Design: Systematic review and meta-analysis
Methods: The Meta-analysis of Observational Studies in Epidemiology reporting guidelines were applied. The Newcastle-Ottawa scale was used to evaluate the risk of bias in the included cohort studies that examined the association of AMD with subsequent dementia or AD. We estimated the pooled hazard ratios (HRs) of dementia or AD using random-effects model meta-analysis and subgroup analysis on different follow-up periods, AMD subtype, gender, age, study design, and methods to ascertain dementia or AD.
Results: A total of 8,223,581 participants were included in 8 studies published during 2000-2021. The meta-analysis showed that AMD was significantly associated with subsequent dementia (pooled HRs, 1.22; 95% confidence interval [CI], 1.01-1.47) or AD (pooled HRs, 1.21; 95% CI, 1.03-1.43). Our secondary analysis revealed that the association was more noticeable in dry AMD than wet AMD.
Conclusions: Patients with AMD have higher risks of developing dementia or AD, and therefore identifying related comorbidities and retinal biomarkers is much warranted for older adults with AMD in ophthalmological practice. PROSPERO Registration number: CRD42022310764.
Rates of choroidal loss and ganglion cell-inner plexiform layer thinning in type 2 diabetes mellitus and healthy individuals: a 2-year prospective study.
The British Journal of Ophthalmology. 2022 Nov 16
Hui Z, Guo X, Bulloch G, Yuan M, Xiong K, Zhang S, Chen Y, Li Y, Liao H, Huang W, Zhu Z, Wang W.
Aims: To investigate longitudinal choroid and ganglion cell-inner plexiform layer (GCIPL) changes in type 2 diabetes mellitus (T2DM) patients and healthy populations across 2 years.
Methods: This prospective cohort study included T2DM patients and healthy controls. T2DM patients were divided into mild non-proliferative diabetic retinopathy (NPDR) or non-DR (NDR) groups. Macular choroidal and GCIPL thickness was measured using swept-source optical coherence tomography at baseline and follow-up after 2 years. A linear-mixed effect model compared rates of change in choroidal and GCIPL thicknesses between the three groups.
Results: 895 T2DM patients (770 in the NDR group and 125 in the NPDR group) and 847 healthy controls were included. Following 2 years, choroidal thinning occurred at a rate of -7.7±9.2 µm/year, -8.1±8.7 µm/year and -5.2±8.1 µm/year in NDR, NPDR and control groups, respectively (p<0.001). GCIPL loss occurred quickest in NPDR patients (-0.97±0.97 µm/year), followed by NDR (-0.91±0.89 µm/year) and the control group (-0.04±0.55 µm/year) (p<0.001). Following multivariate adjustment, choroidal thinning was -2.04 µm/year (95% CI: -4.05 to -0.03; p=0.047) and -1.95 µm/year (95% CI: -3.14 to -0.75; p=0.001) faster in NPDR and NDR groups than in the control group, respectively, and GCIPL thinning was -1.02 µm/year (95% CI: -1.19 to -0.84; p<0.001) and -0.88 µm/year (95% CI: -0.98 to -0.78; p<0.001) faster in the NPDR and NDR groups than in the control group, respectively.
Conclusion: Progressive choroidal and GCIPL thinning occurs in healthy individuals and T2DM patients; however, T2DM undergoes accelerated choroidal and GCIPL loss in NPDR patients.
NUTRITION AND LIFESTYLE
What Advice Is Currently Given to Patients with Age-Related Macular Degeneration (AMD) by Eyecare Practitioners, and How Effective Is It at Bringing about a Change in Lifestyle? A Systematic Review.
Nutrients. 2022 Nov 3
Dave S, Binns A, Vinuela-Navarro V, Callaghan T.
There is currently no treatment for early/intermediate Age-related Macular Degeneration (AMD) but Eye Care Professionals (ECPs) are recommended to advise patients about modifiable lifestyle factors, including dietary changes, that can slow disease progression. The aim of this review was to understand advice currently given to patients with AMD by ECPs and to evaluate evidence regarding patient compliance. A systematic review was conducted of literature published in electronic databases: CINAHL, MEDLINE, PsycINFO, PyscARTICLES, EMBASE, AMED. Methods followed PRISMA guidelines (PROSPERO registration number: CRD42020223724). Twenty-four reports were eligible for inclusion, 12 focused on ECP experience, 7 on patient experience, and 6 on impact of advice (one paper reported on the ECP and patient experience). Studies reported that a substantial proportion of patients did not recall receiving lifestyle modification advice from their ECP (57.95%, range 2-95% across patient based studies). Practitioners were most likely to provide advice about nutritional supplements (80%, range 67-93% across ECP studies), and least likely about smoking (44%, range 28-71% across ECP studies), however supplements advised did not always comply with evidence-based guidelines. The main reason for patients not following lifestyle advice was lack of provision by the ECP (54.5%, range 21-94% across studies on the impact of advice). The review highlighted a need for more studies to understand patient preferences for receiving advice and research on ECP perceived barriers to advice provision.
Journal of Psychiatric Practice
Balsara C, Shahin A, Baviriseaty N, Czuma R, Sullivan GA.
Charles Bonnet syndrome (CBS) is a disorder of visual hallucinations in psychologically normal patients with ocular disease or damage to visual pathways. The etiology of CBS is not fully understood. It is associated with various triggers, with age-related macular degeneration the most common; other triggers are systemic diseases such as stroke, multiple sclerosis, and anemia as well as lighting issues, fatigue, and medical or surgical eye treatments. Visual disturbances such as decreased visual acuity, visual field deficits, or visual hallucinations are common in association with hypertensive encephalopathy. We describe a patient with episodic CBS triggered by recurrent hypertensive crises, which resolved with blood pressure management in the hospital setting.
Early onset monocular hydroxychloroquine maculopathy in a systemic lupus erythematosus patient with history of central retinal artery occlusion: a case report.
BMC Ophthalmology. 2022 Nov 14
Ameen Ismail A, Sadek SH, Hatata RM.
Background: Hydroxychloroquine is a widely used medication for various clinical conditions mainly rheumatological and dermatological autoimmune diseases e.g. systemic lupus erythematosus, rheumatoid arthritis and psoriasis. While it is considered a safe medication, it is well-established that it can cause retinal toxicity i.e. HCQ maculopathy. Guidelines for HCQ retinal toxicity screening include factors like body weight, daily dose, duration, systemic diseases and retinal diseases. In this case study, we report a specific association between CRAO as a retinal disease and early onset HCQ maculopathy in a SLE patient.
Case presentation: A 42-year-old Caucasian female SLE patient presented with a complaint of gradual progressive painless diminution of vision in the left eye that started 16 months earlier. Clinical evaluation of the patient revealed a history of sudden profound painless diminution of vision in the same eye 18 months earlier after which the patient experienced only partial improvement of vision. That episode of sudden diminution of vision was attributed to left CRAO, complicating SLE-related thrombophilia, confirmed by fundus fluorescein angiography. Based on that diagnosis, the patient had been prescribed HCQ. At the time of presentation, fundus examination revealed left bull’s eye maculopathy and right normal fundus. Therefore, a diagnosis of HCQ maculopathy in the left eye was made after exclusion of other causes of unilateral bull’s eye maculopathy.
Conclusion: Our case study is the first to report an association between CRAO as a specific retinal disease and early onset of HCQ maculopathy in a SLE patient. The unilateral bull’s eye presentation which occurred in the eye with CRAO after only 16 months of HCQ treatment highly suggests that CRAO is probably the cause of such unusually early maculopathy. This case report highlights the importance of retinal diseases as risk factors for HCQ maculopathy. It also points out the lack of specific evidence concerning the association between specific retinal diseases and HCQ maculopathy.