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    Research Update 567


    Risk Factors For Poorer Quality Of Life In Patients With Neovascular Age-Related Macular Degeneration: A Longitudinal Clinic-Based Study.

    Eye (London, England) 2023 Jan 25.

    Vu KV, Mitchell P, Detaram HD, Burlutsky G, Liew G, Gopinath B.

    Background/Objectives: To examine the risk factors for poor vision-related and health-related quality of life (QoL) in patients with neovascular age-related macular degeneration (nAMD) who present for anti-vascular endothelial growth factor (anti-VEGF) therapy.

    Methods: In a clinic-based cohort of 547 nAMD patients who presented for treatment, the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ25), Short-Form 36 (SF-36) and EuroQoL EQ-5D-5L questionnaires were administered to assess vision-related and health-related QoL. Of these, 83 participants were followed up one-year later to provide longitudinal data.

    Results: Individuals with mild or moderate visual impairment or blindness at baseline had significantly lower NEI-VFQ-25 scores at follow-up. The presence of ≥3 chronic diseases was associated with lower SF-36 mental component scores (MCS) (p = 0.04) and EQ-VAS scores (p = 0.05). Depressive symptoms were associated with significantly lower MCS (p < 0.0001) and EQ-VAS scores (p = 0.02). Individuals with versus without impaired basic activities of daily living (ADLs) exhibited NEI-VFQ-25 and EQ-VAS scores that were 10.96 (p = 0.03) and 0.13 (p = 0.02) points lower. Those with impaired instrumental ADLs scored 11.62 (p = 0.02), 13.13 (p < 0.0001) and 15.8 (p = 0.0012) points lower in the NEI-VFQ-25, SF-36 physical component score and EQ-5D-5L summary score, respectively.

    Conclusions: The QoL of nAMD patients is affected by visual acuity as well as patients’ medical history, mental health and functional status.

    DOI: 10.1038/s41433-023-02407-0


    Impact of Retinal Fluid-Free Months On Outcomes In Namd: A Treatment Agnostic Analysis Of The HAWK and HARRIER Studies.

    Retina, (Philadelphia,Pa). 2022 Dec 20.

    Eichenbaum D, Brown DM, Ip M, Khanani AM, Figueroa MS, McAllister IL, Laude A, Guruprasad B, Tang S, Gmeiner B, Clemens A, Souied E.

    Purpose: To assess the effect of the total number of fluid-free months after loading on visual and anatomical outcomes in neovascular age-related macular degeneration (nAMD) patients receiving anti-vascular endothelial growth factor (anti-VEGF) therapy.

    Methods: This post-hoc analysis pooled patient-level data from the brolucizumab 6 mg (n=718) and aflibercept 2 mg (n=715) arms of the HAWK and HARRIER randomized clinical trials. Based on data from Weeks 12 to 96, patients were assigned to one of 5 categories based on fluid-free visits (FFV; the total number of monthly visits at which they were observed to be without retinal fluid). Three definitions of ‘fluid-free’ were explored based on the location of the fluid observed.

    Results: Patients allocated to categories 4 (15-21 FFV) and 5 (22 FFV, always dry) consistently had the best visual and anatomical outcomes at Week 96, while patients allocated to categories 1 (0 FFV, never dry) and 2 (1-7 FFV) consistently had the worst visual and anatomical outcomes. Variability in retinal thickness over time was lowest in categories 4 and 5.

    Conclusion: Absence of retinal fluid at more visits after loading has a positive association with visual and anatomic outcomes in nAMD patients, regardless of fluid type.

    DOI: 10.1097/IAE.0000000000003699

    Five-year Incidence Of Fellow Eye Neovascular Involvement In Age-Related Macular Degeneration And Polypoidal Choroidal Vasculopathy In An Asian Population.

    Retina (Philadelphia, Pa). 2023 Feb 1;

    Teo KYC, Vyas C, Sun C, Cheong KX, Chakravarthy U.

    Purpose: To assess 5-year cumulative incidence and risk factors of fellow eye involvement in Asian neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy.

    Methods: In a prospective cohort study of Asian nAMD and polypoidal choroidal vasculopathy, the fellow eyes were evaluated for exudation. The 5-year incidence of exudation was compared between nAMD and polypoidal choroidal vasculopathy.

    Results: A total of 488 patients were studied. The 5-year incidence of exudation in fellow eyes was 16.2% (95% confidence interval: 12.0-20.2). Polypoidal choroidal vasculopathy compared with nAMD in the first eye was associated with lower fellow eye progression (9.8% [95% confidence interval: 5.1-14.3]) vs. 22.9% [95% confidence interval: 15.8-29.3], P < 0.01). Drusen (hazards ratio 2.11 [95% confidence interval: 1.10-4.06]), shallow irregular retinal pigment epithelium elevation (2.86 [1.58-5.18]), and pigment epithelial detachment (3.01 [1.27-7.17]) were associated with greater progression. A combination of soft drusens and subretinal drusenoid deposits, and specific pigment epithelial detachment subtypes (multilobular, and sharp peaked) were associated with progression. Pigment epithelial detachment, shallow irregular retinal pigment epithelium elevation, and new subretinal hyperreflective material occurred at 10.4 ± 4.2 months, 11.1 ± 6.0 months, and 6.9 ± 4.3 months, respectively, before exudation.

    Conclusion: The 5-year incidence of fellow eye involvement in Asian nAMD is lower than among Caucasians because of a higher polypoidal choroidal vasculopathy prevalence. Drusens, shallow irregular retinal pigment epithelium elevation, and pigment epithelial detachment are risk factors for fellow eye progression.

    DOI: 10.1097/IAE.0000000000003666


    Associations Between Serial Intravitreal Injections And Dry Eye.

    Ophthalmology. 2023 Jan 21:

    Malmin A, Thomseth VM, Forland PT, Khan AZ, Hetland HB, Chen X, Haugen IK, Utheim TP, Forsaa VA.

    Purpose: To investigate the effects of serial intravitreal injections (IVI) on the ocular surface and meibomian glands (MG) in patients treated with anti-vascular endothelial growth factor (anti-VEGF) for neovascular age-related macular degeneration (nAMD).

    Design: Retrospective controlled observational study.

    Subjects: Patients with nAMD receiving unilateral IVI with anti-VEGF agents. The fellow eye was used as control.

    Methods: Tear film and ocular surface examinations were performed on a single occasion at a minimum of four weeks after IVI. A pre-IVI asepsis protocol with povidone-iodine was applied.

    Main Outcome Measures: Upper and lower MG loss, tear meniscus height (TMH), bulbar redness score (BR), non-invasive tear break-up time (NIBUT), tear film osmolarity (TOsm), Schirmer test, corneal staining, fluorescein tear film break-up time (TBUT), meibomian gland expressibility (ME) and meibum quality (MQ).

    Results: Ninety patients with a mean age of 77.5 years (SD 8.4; range 54-95) were included. The median number of IVI in treated eyes was 19.5 (range 2-132). Mean MG loss in the upper eyelid was 19.1 (SD 11.3) % in treated eyes and 25.5 (SD 14.6) % in untreated fellow eyes (P=0.001). For the lower eyelid, median MG loss was 17.4 (IQR 9.4-29.9) % in treated eyes and 24.5 (IQR 14.2-35.2) % in fellow eyes (P<0.001). Mean BR was 1.32 (SD 0.46) in treated eyes versus 1.44 (SD 0.45) in fellow eyes (P=0.017). Median TMH was 0.36 (IQR 0.28-0.52) mm in treated eyes and 0.32 (IQR 0.24-0.49) mm in fellow eyes (P=0.02). There were no differences between treated and fellow eyes regarding NIBUT, TOsm, Schirmer test, corneal staining, fluorescein TBUT, meibomian gland expressibility ME or MQ.

    Conclusions: Repeated IVI with anti-VEGF with preoperative povidone-iodine application was associated with reduced meibomian gland loss, increased tear volume and reduced signs of inflammation compared to fellow non-treated eyes in patients with nAMD. This regimen may thus have a beneficial effect on the ocular surface.

    DOI: 10.1016/j.ophtha.2023.01.009


    Retinopathy During the First 5 Years of Type 1 Diabetes and Subsequent Risk of Advanced Retinopathy.

    Diabetes Care. 2022 Dec 13.

    Malone JI, Gao X, Lorenzi GM, Raskin P, White NH, Hainsworth DP, Das A, Tamborlane W(8), Wallia A, Aiello LP, Bebu I; Diabetes Control and Complications Trial (DCCT)-Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group.

    Objective: To determine whether individuals with type 1 diabetes (T1D) who develop any retinopathy at any time prior to 5 years of diabetes duration have an increased subsequent risk for further progression of retinopathy or onset of proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), diabetes-related retinal photocoagulation, or anti-vascular endothelial growth factor injections. Additionally, to determine the influence of HbA1c and other risk factors in these individuals.

    Research Design and Methods: Diabetic retinopathy (DR) was assessed longitudinally using standardized stereoscopic seven-field fundus photography at time intervals of 6 months to 4 years. Early-onset DR (EDR) was defined as onset prior to 5 years of T1D duration. Cox models assessed the associations of EDR with subsequent risk of outcomes.

    Results: In unadjusted models, individuals with EDR (n = 484) had an increased subsequent risk of PDR (hazard ratio [HR] 1.51 [95% CI 1.12, 2.02], P = 0.006), CSME (HR 1.44 [1.10, 1.88], P = 0.008), and diabetes-related retinal photocoagulation (HR 1.48 [1.12, 1.96], P = 0.006) compared with individuals without EDR (n = 369). These associations remained significant when adjusted for HbA1c, but only the association with PDR remained significant after adjustment for age, duration of T1D, HbA1c, sex, systolic/diastolic blood pressure, pulse, use of ACE inhibitors, albumin excretion rate, and estimated glomerular filtration rate (HR 1.47 [95% CI 1.04, 2.06], P = 0.028).

    Conclusions: These data suggest that individuals with any sign of retinopathy within the first 5 years of T1D onset may be at higher risk of long-term development of advanced DR, especially PDR. Identification of early-onset DR may influence prognosis and help guide therapeutic management to reduce the risk of future visual loss in these individuals.

    DOI: 10.2337/dc22-1711


    Quantitative Assessment Of Automated Optical Coherence Tomography Image Analysis Using A Home-Based Device For Self-Monitoring Neovascular Age-Related Macular Degeneration.

    Retina (Philadelphia, Pa). 2022 Nov 17

    Oakley JD, Verdooner S, Russakoff DB, Brucker AJ, Seaman J, Sahni J, Domenico CB, Cozzi M, Rogers J, Staurenghi G.

    Purpose: To evaluate a prototype home optical coherence tomography (OCT) device and automated analysis software for detection and quantification of retinal fluid relative to manual human grading in a neovascular age-related macular degeneration patient cohort.

    Methods: Patients undergoing anti-vascular endothelial growth factor therapy were enrolled in this prospective observational study. In 136 OCT scans from 70 patients using the prototype home OCT device, fluid segmentation was performed using automated analysis software and compared with manual gradings across all retinal fluid types using receiver-operating characteristic (ROC) curves. The Dice similarity coefficient (DSC) was used to assess the accuracy of segmentations, and correlation of fluid areas quantified endpoint agreement.

    Results: Fluid detection per B-scan had area under the ROC curves of 0.95, 0.97, and 0.98 for intraretinal fluid (IRF), subretinal fluid (SRF), and subretinal pigment epithelium (sub-RPE) fluid, respectively. On a per volume basis, the values for IRF, SRF, and sub-RPE fluid were 0.997, 0.998, and 0.998, respectively. Average DSC values across all B-scans were 0.64, 0.73, and 0.74, and the coefficients of determination were 0.81, 0.93, and 0.97 for IRF, SRF, and sub-RPE fluid, respectively.

    Conclusion: Home OCT device images assessed using the automated analysis software showed excellent agreement to manual human grading.

    DOI: 10.1097/IAE.0000000000003677


    Effective smMIPs-Based Sequencing of Maculopathy-Associated Genes in Stargardt Disease Cases and Allied Maculopathies from the UK.

    Genes. 2023 Jan 11;

    Mc Clinton B, Corradi Z, McKibbin M, Panneman DM, Roosing S, Boonen EGM, Ali M, Watson CM, Steel DH, Cremers FPM, Inglehearn CF, Hitti-Malin RJ, Toomes C.

    Macular dystrophies are a group of individually rare but collectively common inherited retinal dystrophies characterised by central vision loss and loss of visual acuity. Single molecule Molecular Inversion Probes (smMIPs) have proved effective in identifying genetic variants causing macular dystrophy. Here, a previously established smMIPs panel tailored for genes associated with macular diseases has been used to examine 57 UK macular dystrophy cases, achieving a high solve rate of 63.2% (36/57). Among 27 bi-allelic STGD1 cases, only three novel ABCA4 variants were identified, illustrating that the majority of ABCA4 variants in Caucasian STGD1 cases are currently known. We examined cases with ABCA4-associated disease in detail, comparing our results with a previously reported variant grading system, and found this model to be accurate and clinically useful. In this study, we showed that ABCA4-associated disease could be distinguished from other forms of macular dystrophy based on clinical evaluation in the majority of cases (34/36).

    DOI: 10.3390/genes14010191


    Sleep Duration And The Risk Of Major Eye Disorders: A Systematic Review And Meta-Analysis.

    Eye (London, England). 2023 Jan 23

    Zhou M, Li DL, Kai JY, Zhang XF, Pan CW.

    Background: To assess the relationship between sleep duration and the risk of major eye disorders including myopia, glaucoma, cataract, age-related macular degeneration (AMD), and diabetic retinopathy (DR).

    Methods: Databases including PubMed, Embase, Web of Science, and Cochrane library were searched for eligible publications before July 2021. Studies assessing the relationship between sleep duration and any one of the major eye disorders were identified. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were estimated using random-effects models.

    Results: We identified 21 relevant articles including 777348 participants, and 17 were cross-sectional, 3 were longitudinal, and 1 was case-control. Pooled results indicated that long sleep duration was significantly associated with the risk of DR (OR = 1.84, 95% CI 1.24, 2.73), and short sleep duration was significantly associated with the risk of cataract (OR = 1.20, 95% CI 1.05, 1.36). Besides, a significant relationship was observed between the risk of DR and long sleep duration per day (i.e., nighttime sleep plus daytime napping, OR = 1.74, 95% CI 1.23, 2.44) rather than per night (OR = 2.17, 95% CI 0.95, 4.99). The extreme of long sleep duration (i.e., >10 h per night) increased the risk of myopia (OR = 1.02, 95% CI 1.01, 1.04).

    Conclusions: Inappropriate sleep duration might increase the risk of major eye disorders. The findings could contribute to the growing knowledge on the possible relationship between circadian rhythms and eye disorders.

    DOI: 10.1038/s41433-023-02403-4