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    Research update: 534

    The latest research highlights for 19 April 2022.


    Association of Fenofibrate Use and the Risk of Progression to Vision-Threatening Diabetic Retinopathy.

    JAMA Ophthalmology. 2022 Apr 7

    Meer E, Bavinger JC, Yu Y, VanderBeek BL.

    Importance: Diabetic retinopathy (DR) may progress from nonproliferative DR (NPDR) to vision-threatening DR (VTDR). Studies have investigated fenofibrate use as a protective measure with conflicting results, and fenofibrate is not typically considered by ophthalmologists in the management of DR currently.

    Objective: To assess the association between fenofibrate use and the progression from NPDR to VTDR, proliferative DR (PDR), or diabetic macular edema (DME).

    Design, setting, and participants: This multicenter cohort study used medical claims data from a large US insurer. Cohorts were created from all patients with NPDR 18 years or older who had laboratory values from January 1, 2002, to June 30, 2019. Exclusion criteria consisted of any previous diagnosis of PDR, DME, proliferative vitreoretinopathy, or treatment used in the care of VTDR. Patients were also excluded if they had a diagnosis of VTDR within 2 years of insurance plan entry, regardless of when NPDR was first noted in the plan.

    Exposures: Fenofibrate use.

    Main outcomes and measures: The main outcomes were a new diagnosis of VTDR (a composite outcome of either PDR or DME) or DME and PDR individually. A time-updating model for all covariates was used in multivariate Cox proportional hazard regression to determine hazards of progressing to an outcome. Additional covariates included NPDR severity scale, systemic illnesses, demographics, kidney function (based on estimated glomerular filtration rate level), hemoglobin A1c, hemoglobin, and insulin use.

    Results: A total of 5835 fenofibrate users with NPDR at baseline (mean [SD] age, 65.3 [10.4] years; 3564 [61.1%] male; 3024 [51.8%] White) and 144 417 fenofibrate nonusers (mean [SD] age, 65.7 [12.3] years; 73 587 [51.0%] male; 67 023 [46.4%] White) were included for analysis. Of these, 27 325 (18.2%) progressed to VTDR, 4086 (2.71%) progressed to PDR, and 22 750 (15.1%) progressed to DME. After controlling for all covariates, Cox model results showed fenofibrates to be associated with a decreased risk of VTDR (hazard ratio, 0.92 [95% CI, 0.87-0.98]; P = .01) and PDR (hazard ratio, 0.76 [95% CI, 0.64-0.90]; P = .001) but not DME (hazard ratio, 0.96 [95% CI, 0.90-1.03]; P = .27).

    Conclusions and relevance: In this study, fenofibrate use was associated with a decreased risk of PDR and VTDR but not DME alone. These findings support the rationale for additional clinical trials to determine if these associations may be representative of a causal relationship between fenofibrate use and reduced risk of PDR or VTDR.

    DOI: 10.1001/jamaophthalmol.2022.0633


    Longer Term Visual Outcomes in Neovascular AMD, Diabetic and Vein Occlusion Related Macular Edema: Clinical Outcomes in 130,247 Eyes.

    Ophthalmology Retina. 2022 Apr 2

    Ciulla TA, Hussain RM, Taraborelli D, Pollack J, Williams DF.

    Purpose: Clinical practice visual acuity (VA) outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy up to 5 years were assessed in neovascular AMD (nAMD), diabetic macular edema (DME), and branch and central retinal vein occlusion (BRVO, CRVO)-related macular edema (ME).

    Design: Retrospective analysis was performed using the Vestrum Health Retina Database. PARTICIPANTS: Treatment naïve nAMD, DME, BRVO-ME and CRVO-ME patients who received anti-VEGF injections between 2014-2019, with follow-up data ≥ 12 months.

    Methods: Age, gender, number of anti-VEGF treatments, and VA data were analyzed.

    Main outcome measure: Mean VA change up to 3 years (BRVO-ME, CRVO-ME) and 5 years (nAMD and DME).

    Results: At 1, 3 and 5 years, in those 67,666, 21,305 and 5,208 eyes with nAMD, after a mean of 7.6, 19.5 and 32 injections, there was a mean change of +3.1, -0.2 and -2.2 letters, respectively. At 1, 3 and 5 years, in those 40,832, 7,728 and 1,192 eyes with DME, after a mean of 6.2, 15.4 and 26.0 injections, there was a mean change of +4.7, +3.3 and +3.1 letters, respectively. At 1 and 3 years, in those 12,451 and 3,027 eyes with BRVO-ME, after a mean of 7.1 and 18.2 injections, there was a mean change of +9.5 and +7.7 letters, respectively. At 1 and 3 years, in those 9,298 and 2,264 eyes with CRVO-ME, after a mean of 7.3 and 18.8 injections, there was a mean change of +8.3 and +6.0 letters, respectively. (P <0.01 for all VA changes >1 letter). In all 4 conditions, mean VA increased with mean number of anti-VEGF injections, eyes with baseline VA of 20/40 or better tended to lose VA, and those with progressively worse baseline VA experienced progressively greater VA gain at 3 years.

    Conclusions: In practice, patients with nAMD, DME, BRVO-ME and CRVO-ME show limited visual outcomes, with nAMD patients tending to lose VA at 3 and 5 years. Across all 4 disorders, mean change in VA correlates with treatment intensity at 1, 3 and 5 years. Patients with better baseline VA are more vulnerable to vision loss.

    DOI: 10.1016/j.oret.2022.03.021


    Treatment of diabetic macular edema in real-world clinical practice: the effect of aging.

    Journal Diabetes Investigation. 2022 Apr 7

    Kusuhara S, Shimura M, Kitano S, Sugimoto M, Muramatsu D, Fukushima H, Takamura Y, Matsumoto M, Kokado M, Kogo J, Sasaki M, Morizane Y, Utsumi T, Kotake O, Koto T, Terasaki H, Hirano T, Ishikawa H, Mitamura Y, Okamoto F, Kinoshita T, Kimura K, Yamashiro K, Suzuki Y, Hikichi T, Washio N, Sato T, Ohkoshi K, Tsujinaka H, Kondo M, Takagi H, Murata T, Sakamoto T; Japan Clinical Retina Study (J-CREST) group.

    Aims/introduction: In older patients, the management of diabetic macular edema (DME) would be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME.

    Materials and methods: This is a real-world clinical study including 1552 patients with treatment-naïve center-involved DME. Patients were categorized by age at baseline (C1, <55; C2, 55-64; C3, 65-74; and C4, ≥75 years). The outcomes were change in logarithm of the minimum angle of resolution best-corrected visual acuity (logMAR BCVA) and central retinal thickness (CRT) and number of treatments from baseline to 2 years.

    Results: From baseline to 2 years, the mean changes in logMAR BCVA from baseline to 2 years were -0.01 in C1, -0.06 in C2, -0.07 in C3, and 0.01 in C4 (P = 0.016), and the mean changes in CRT were -136.2 μm in C1, -108.8 μm in C2, -100.6 μm in C3, and -89.5 μm in C4 (P = 0.008). Treatments applied in the 2-year period exhibited decreasing trends with increasing age category on the number of intravitreal injections of anti-VEGF agents (P = 0.06), selecting local corticosteroid injection (P = 0.031), vitrectomy (P < 0.001), and laser photocoagulation outside the great vascular arcade (P < 0.001).

    Conclusions: Compared with younger patients with DME, patients with DME aged ≥75 years showed less frequent treatment, lower BCVA gain, and smaller CRT decrease. The management and visual outcome in older patients with DME would be unsatisfactory in real-world clinical practice.

    DOI: 10.1111/jdi.13801

    Functional and structural characteristics in patients with diabetic macular oedema after switching from ranibizumab to aflibercept treatment. Three year results in real world settings.

    International Journal of Retina and Vitreous. 2022 Apr 1

    Sepetis AE, Clarke H, Gupta B.

    Background: Our aim was to examine the long term anatomical and functional outcomes in patients with refractory diabetic macular oedema (DMO) undergoing treatment switch from ranibizumab to aflibercept.

    Methods: Retrospective review of patients with DMO undergoing treatment switch from ranibizumab to aflibercept at a single centre between 2015 and 2017. Primary outcomes were best corrected visual acuity (BCVA) and central macular thickness (CMT).

    Results: 57 eyes from 44 patients were included. Following switch to aflibercept, median (IQR) BCVA improved to 73 (64-77) letters at 3 months (p = 0.0006), to 73 (61-78) letters at 6 months (p = 0.0042), to 73 (65-77) at 9 months (p = 0.0006), and to 73 (63-75) letters at 18 months (p = 0.0444). At 36 months following switch, 12 eyes had gained > 10 letters, 5 eyes had gained 5-9 letters, 25 remained stable (± 5 letters), 7 eyes lost 5-9 letters and 8 eyes lost > 10 letters. A significant reduction in CMT at all trimesters following treatment switch was found except at month 24.

    Conclusions: We provide real world data suggesting a sustained anatomical and functional benefit of switching from ranibizumab to aflibercept in the treatment of refractory DMO.

    DOI: 10.1186/s40942-022-00373-5

    Predictors of vision-related quality of life in patients with macular oedema receiving intra-vitreal anti-VEGF treatment.

    Ophthalmic Physiology Opt. 2022 Apr 2

    Rausch-Koster PT, Rennert KN, Heymans MW, Verbraak FD, van Rens GHMB, van Nispen RMA.

    Purpose: To determine which demographic and clinical characteristics are predictive of vision-related quality of life (VrQoL) and quality of life (QoL) in patients with macular oedema receiving intravitreal anti-vascular endothelial growth factor (VEGF) treatment.

    Methods: Vision-related quality of life (VrQoL) and quality of life (QoL) were measured in 712 patients with retinal exudative disease receiving anti-VEGF treatment at baseline, 6 and 12 months. VrQoL was measured using an item-response theory based 47-question item bank (EyeQ), whereas QoL was measured using the EuroQol Five Dimensions (EQ-5D) questionnaire. The EQ-5D score was dichotomized into a perfect score of 1 and a suboptimal score of <1. Demographic and clinical patient characteristics were considered as possible predictors of (Vr)QoL. Prediction models for (Vr)QoL were created with linear mixed models and generalised estimating equations, using a forward selection procedure.

    Results: A worse VrQoL was predicted by poorer LogMAR visual acuity of the better eye, female sex, single civil status, older age, longer length of anti-VEGF treatment at baseline and the presence of non-ocular and ocular comorbidities. Suboptimal EQ-5D scores were predicted by poorer LogMAR visual acuity of the better eye, female sex, single civil status, older age, the presence of non-ocular comorbidities and a lower educational background.

    Conclusions: Along with visual acuity of the better eye, which is the main factor used in clinical decision making, other patient characteristics should also be considered for the risk assessment of (Vr)QoL, such as sex, age, civil status, comorbidities and length of anti-VEGF treatment.

    DOI: 10.1111/opo.12984


    Frequency of cystoid macular edema and vitreomacular interface disorders in genetically solved syndromic and non-syndromic retinitis pigmentosa.

    Graefes Archive for Clinical and Experimental Ophthalmology. 2022 Apr 7

    Marques JP, Neves E, Geada S, Carvalho AL, Murta J, Saraiva J, Silva R.

    Purpose: Retinitis pigmentosa (RP) corresponds to a group of inherited retinal disorders where progressive rod-cone degeneration is observed. Cystoid macular edema (CME) and vitreomacular interface disorders (VMID) are known to complicate the RP phenotype, challenging an age-old concept of retained central visual acuity. The reported prevalence of these changes varies greatly among different studies. We aim to describe the frequency of CME and VMID and identify predictors of these changes in a cohort of Caucasian patients with genetically solved syndromic (sRP) and non-syndromic RP (nsRP).

    Methods: Cross-sectional study of patients with genetically solved sRP or nsRP. Genetic testing was clinically oriented in all probands and coordinated by a medical geneticist. The presence/absence of CME and VMIDs such as epiretinal membrane (ERM), vitreomacular traction (VMT), lamellar hole (LH), macular hole (MH), and macular pseudohole (MPH), and the integrity of the neurosensory retina and retinal pigment epithelium were evaluated in individual macular SD-OCT b-scans. Mixed-effects regression analysis models were used to identify significant predictors of BCVA, CME, and VMID. Significance was considered at α < 0.05.

    Results: We included 250 eyes from 125 patients. Mean age was 44.9 ± 15.7 years and 55.2% were male. Eighty-eight patients had nsRP and 37 had sRP. Median BCVA was 0.5 (0.2-1.3) logMAR. CME was found in 17.1% of eyes, while ERM was found in 54.3% of eyes. The frequency of CME (p = 0.45) and ERM (p = 0.07) did not differ between sRP and nsRP patients, nor across different inheritance patterns. Mixed-effects univariate linear regression identified age (p = 0.04), cataract surgery (p < 0.01), and loss of integrity of outer retinal layers (p < 0.01) as significant predictors of lower visual acuity, while increased foveal thickness (p < 0.01) and the presence of CME (p = 0.04) were predictors of higher visual acuity. On mixed-effects multivariable analysis, only increased foveal thickness was significantly associated with better visual acuity (p < 0.01).

    Conclusion: We found that the burden of ERM and CME in RP patients is high, highlighting the importance of screening for these potentially treatable conditions to improve the quality of life of RP patients.

    DOI: 10.1007/s00417-022-05649-y


    Improvement of pseudophakic cystoid macular edema with subconjunctival injections of interferon α2b:a case report.

    American Journal Ophthalmology Case Rep. 2022 Mar 23

    Aghaei H, Es’haghi A, Pourmatin R.

    Purpose: To report a patient with resistant cystoid macular edema after an uneventful phacoemulsification cataract surgery who responded to subconjunctival interferon α2b injections.

    Observations: This report describes a 60-year-old male patient with pseudophakic cystoid macular edema that was unresponsive to multiple courses of topical non-steroidal anti-inflammatory drugs and steroids during the follow-up period. Weekly subconjunctival interferon α2b (5 MIU/ml) was administered four times. Cystoid macular edema completely resolved after the 4th injection. During a six-month follow-up period, cystoid macular edema did not recur. No adverse local and systemic side effects were observed.

    Conclusions and importance: Weekly subconjunctival interferon α2b injections might be a safe and effective treatment modality in the treatment of stubborn pseudophakic cystoid macular edema to conventional treatment.

    © 2022 Published by Elsevier Inc.

    DOI: 10.1016/j.ajoc.2022.101504


    Neovascular Age-Related Macular Degeneration (nAMD): A Review of Emerging Treatment Options.

    Clinical Ophthalmology. 2022 Mar 25

    Tan CS, Ngo WK, Chay IW, Ting DS, Sadda SR.

    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.

    DOI: 10.2147/OPTH.S231913