FEATURED ARTICLE
Estimating excess visual loss from neovascular age-related macular degeneration in the UK during the COVID-19 pandemic: a retrospective clinical audit and simulation model.
BMJ Open. 2022 Apr 15
Thomas DS, Warwick A, Olvera-Barrios A, Egan C, Schwartz R, Patra S, Eleftheriadis H, Khawaja A, Lotery A, Muller PL, Hamilton R, Preston E, Taylor P, Tufail A; UK EMR Users Group.
Objectives: To report the reduction in new neovascular age-related macular degeneration (nAMD) referrals during the COVID-19 pandemic and estimate the impact of delayed treatment on visual outcomes at 1 year.
Design: Retrospective clinical audit and simulation model.
Setting: Multiple UK National Health Service (NHS) ophthalmology centres.
Participants: Data on the reduction in new nAMD referrals were obtained from four NHS Trusts comparing April 2020 with April 2019. To estimate the potential impact on 1-year visual outcomes, a stratified bootstrap simulation model was developed drawing on an electronic medical records dataset of 20 825 nAMD eyes from 27 NHS Trusts.
Main outcome measures: Simulated mean visual acuity and proportions of eyes with vision ≤6/60, ≤6/24 and ≥6/12 at 1 year under four hypothetical scenarios: 0-month, 3-month, 6-month and 9-month treatment delays. Estimated additional number of eyes with vision ≤6/60 at 1 year nationally. Results: The number of nAMD referrals dropped on average by 72% (range 65%-87%). Simulated 1-year visual outcomes for 1000 nAMD eyes with a 3-month treatment delay suggested an increase in the proportion of eyes with vision ≤6/60 from 15.5% (13.2%-17.9%) to 23.3% (20.7%-25.9%), and a decrease in the proportion of eyes with vision ≥6/12 (driving vision) from 35.1% (32.1%-38.1%) to 26.4% (23.8%-29.2%). Outcomes worsened incrementally with longer modelled delays. Assuming nAMD referrals are reduced to this level for 1 month nationally, these simulated results suggest an additional 186-365 eyes with vision ≤6/60 at 1 year.
Conclusions: We report a large decrease in nAMD referrals during the COVID-19 lockdown and provide an important public health message regarding the risk of delayed treatment. As a conservative estimate, a treatment delay of 3 months could lead to a >50% relative increase in the number of eyes with vision ≤6/60 and 25% relative decrease in the number of eyes with driving vision at 1 year.
DOI: 10.1136/bmjopen-2021-057269
RISK FACTORS
The risk for developing vision threatening diabetic retinopathy is influenced by heredity to diabetes.
Current Eye Research 2022 Apr 18
Bek T.
Purpose: Clustering of vision threatening diabetic retinopathy within specific families can be the result of similarities in life style but may also be due to a common genetic background. An evaluation of the role of heredity for the development of diabetic retinopathy may help adjusting control intervals in screening programmes to each patient’s individual risk profile.
Methods: Survival analysis was used to study whether family history of diabetes among men and women with type 1 or type 2 diabetes together with the degree of heredity could be added as risk factors to improve the prediction of the risk for developing proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). The study was conducted on data from 12,281 patients followed in the Aarhus area, Denmark, from January 1. 2003 to July 1. 2019.Results: The risk for developing PDR was significantly reduced 2-11 years after known onset of diabetes in the presence of female family members with type 1 diabetes, and the risk for developing DME significantly increased 4-24 years after onset of diabetes in the presence of family members with type 2 diabetes of any sex. These hereditary factors were independent of other studied risk factors such as previous cataract surgery, age of onset of diabetes, metabolic regulation and blood pressure.
Conclusions: The presence of family members with diabetes affects the risk for developing vision threatening diabetic retinopathy and affects the risk for developing PDR and DME differently. This evidence may help individualizing the control intervals in screening programmes for diabetic retinopathy.
DOI: 10.1080/02713683.2022.2067564
DRUG TREATMENTS AND COMPLICATIONS
Objective evaluation of changes in lens clarity after repeated injections of ranibizumab in patients with neovascular age-related macular degeneration.
Graefe’s Archives for Clinical & Experimental Ophthalmology. 2022 Apr 21.
Altunel O, Irgat SG, Özcura F.
Purpose: To objectively evaluate changes in lens densitometry in eyes with neovascular age-related macular degeneration (n-AMD) treated with repeated intravitreal ranibizumab injections during a 12-month period and to compare the results with those in untreated healthy fellow eyes and healthy control eyes.
Methods: In this prospective study, the 36 treated eyes and the 37 untreated fellow eyes of 38 patients with n-AMD and the 32 control eyes of 32 healthy individuals were analyzed. Lens densitometry was evaluated using the Scheimpflug imaging. All data in both groups regarding lens densitometry were recorded at baseline and 12 months.
Results: The mean densitometry of zone 1 in the treated eyes of patients had increased significantly at 12 months compared with the baseline (baseline: 9.3 ± 1.5, 12 months: 11.9 ± 1.7, p = .004) and was significantly greater than those measurements in the fellow eyes (9.8 ± 1.6 p = .02) and control eyes (9.6 ± 1.9, p = .01) at 12 months as well. There were no significant differences in terms of densitometry values between the fellow and control eyes at baseline and 12 months (for all, p > .05). Conclusions: Our results objectively demonstrate early nuclear lens density changes using with Scheimpflug images in eyes with n-AMD that were treated with repeated ranibizumab injections for 12 months.
DOI: 10.1007/s00417-022-05668-9
Redefining the Spectrum of Pentosan Polysulfate Retinopathy: Multimodal Imaging Findings from a Cross-Sectional Screening Study.
Ophthalmology Retina. 2022 Mar 23.
Dieu AC, Whittier SA, Domalpally A, Pak JW, Voland RP, Boyd KM, Gottlieb JL, Crabtree GS, Giles DL, McAchran SE, Mititelu M.
Purpose: There is growing evidence of a direct association between Pentosan polysulfate (PPS) therapy and the development of macular changes. Using standardized visual acuity testing and multimodal imaging, we investigate the impact on vision and describe an expanded spectrum of imaging findings among PPS users.
Design: Cross-sectional screening study.
Participants: Thirty-nine patients who were current or recent users of PPS.
Methods: Participants underwent a brief eye exam and answered a comprehensive medical and ophthalmic history questionnaire. Color fundus photography, fundus autofluorescence (FAF) and spectral domain optical coherence tomography (SD-OCT) were obtained. Images were evaluated by expert graders at the Wisconsin Reading Center. Abnormalities were categorized as definitive toxicity (DT) if seen on both FAF and SD-OCT and questionable toxicity (QT) if seen on either FAF or SD-OCT.
Main Outcome Measures: Early Treatment Diabetic Retinopathy Study (ETDRS) and Snellen visual acuity (VA), dosage and duration of PPS exposure, prevalence of retinal toxicity on imaging.
Results: Mean ETDRS and Snellen VA of the study cohort was 85 letters and 20/22, respectively. The mean PPS daily dose was 282 mg (88-400 mg), while the mean cumulative dose was 915 g (19-3650 g) over a mean period of 8.8 years (2 months-25 years). 41% of eyes evidenced retinopathy; DT was identified in 24 (31%) eyes and QT in 8 (10%) eyes. Retinal pigment epithelium (RPE) abnormalities (thickening and/or thinning) were present in all DT eyes. RPE atrophy was seen in 7 (9%) eyes. In addition to well-established findings, unique SD-OCT features of this cohort include interdigitation zone abnormalities and the presence of a flying-saucer-type defect. FAF abnormalities were seen in 24 (30.8%) of eyes, with 20 (66.7%) of these exhibiting abnormalities located outside the central subfield and extending beyond the arcades.
Conclusion: Findings from masked grading of multimodal imaging at a centralized reading center suggest a wider phenotypic spectrum of structural abnormalities among patients taking PPS. Macular changes selectively involve the RPE and outer retina, with a range of findings often seen beyond the arcades. The subtle and atypical findings in this cohort should prompt clinicians to consider lowering the threshold for diagnosing PPS retinopathy.
DOI: 10.1016/j.oret.2022.03.016
Dexamethasone Intravitreal Implant Complications Including Vitreous Hemorrhage and Hypotony.
Retina Cases & Brief Reports. 2022 Feb 2.
Yu JJ, Adrean SD.
Purpose: To describe cases of visually significant vitreous hemorrhage (VH) following dexamethasone (DEX) intravitreal implant in our practice and present two cases which required surgical intervention as well as a case of VH and hypotony following DEX implant. We also describe and illustrate an injection technique which may minimize incidence of these complications. Methods: Retrospective case series.
Patients: Three patients with cystoid macular edema treated with DEX implant.
Results: In our practice, the overall incidence of VH was 1.7% (8/467 injections) and those that required surgical intervention was 0.4% (2/467) over a 10 year period, from June 2010 to June 2020 (Table 1). 75% (6/8) VH resolved spontaneously over time, without surgical intervention.
Conclusion: Non-clearing VH and hypotony are rare but serious complications of DEX implant.
DOI: 10.1097/ICB.0000000000001247
Intraocular Pressure Changes After Intravitreal Fluocinolone Acetonide Implant: Results from Four European Countries.
Ophthalmology & Therapy. 2022 Apr 15.
Lebrize S, Arnould L, Bourredjem A, Busch C, Rehak M, Massin P, Barbosa-Breda J, Lupidi M, Mariotti C, Hamza M, Grise-Dulac A, Gabrielle PH, Baillif S, Creuzot-Garcher C.
Introduction: The 0.19 mg fluocinolone acetonide (FAc) intravitreal implant delivers a continuous intravitreal corticosteroid dose for the treatment of refractory diabetic macular oedema (DMO). The aim of this study was to assess the impact of an FAc intravitreal implant on intraocular pressure (IOP).
Methods: We retrospectively collected anonymised data on the patients’ characteristics, DMO treatment, and IOP and IOP-lowering treatments before and after the FAc intravitreal implant between September 2013 and March 2020 in several European centres.
Results: A total of 221 eyes from 179 patients were included. The mean follow-up duration was 13.4 (± 12.5, range 2.4-33.5) months. Overall, 194 eyes (88.2%) had received an intravitreal dexamethasone injection before the FAc intravitreal implant. For 25 eyes (11.3%) there was a history of glaucoma, and 52 eyes (23.5%) had previous IOP-lowering treatment. Mean IOP before injection was 14.7 (3.4) mmHg and increased to 16.9 (3.7) mmHg 12 months after injection (P < 0.0001). During follow-up, 55 eyes (24.9%) required the addition or initiation of topical IOP-lowering medication, only one patient (0.5%) had laser trabeculoplasty and one patient (0.5%) a minimally invasive glaucoma surgery, and no patient required incisional IOP-lowering surgery.
Conclusion: The FAc intravitreal implant led to substantial IOP elevation. This elevation was monitored most of the time with addition or initiation of topical IOP-lowering medication.
DOI: 10.1007/s40123-022-00504-z
Functional outcomes of sustained improvement on Diabetic Retinopathy Severity Scale with intravitreal aflibercept in the VISTA and VIVID trials.
Eye (London). 2022 Apr 19.
Dhoot DS, Moini H, Reed K, Du W, Vitti R, Berliner AJ, Singh RP.
AIMS: To assess time to, cumulative incidence of, and functional benefit of achieving sustained ≥2-step Diabetic Retinopathy Severity Scale (DRSS) improvement in diabetic macular oedema (DMO). METHODS: Post hoc analysis of VISTA/VIVID including eyes with DMO treated with intravitreal aflibercept injections (IAI), 2 mg q4 weeks (2q4, n = 250) or q8 weeks after 5 monthly doses (2q8, n = 249), or laser control (n = 249). Changes from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST) were evaluated in sustained (≥2 consecutive visits) DRSS subgroups (≥1-step worsening, no change, ≥2-step improvement). RESULTS: Time to sustained ≥2-step DRSS improvement was shorter for both the IAI 2q4 and IAI 2q8 groups versus laser (both log-rank p < 0.001). Cumulative incidences of sustained ≥2-step DRSS improvement with IAI 2q4 and IAI 2q8 versus laser were 40.0% and 42.8% versus 15.5% (both p < 0.001) through week 100. Mean differences (95% CI) in BCVA gains from baseline at weeks 52 and 100 between eyes with sustained ≥2-step DRSS improvement versus sustained ≥1-step DRSS worsening were -3.0 (-8.9, 2.9) and 6.2 (0.2, 12.2) letters with laser, and 4.2 (0.8, 7.6) and 4.9 (1.3, 8.4) letters with IAI combined, respectively. Difference (95% CI) in CST reduction was significantly greater only with IAI combined at week 100 (-83.0 [-140.8, -25.3]). Correlations between BCVA and CST changes were weak. CONCLUSIONS: DMO eyes treated with IAI achieved sustained ≥2-step DRSS improvement significantly earlier and more frequently versus laser. This improvement was associated with greater BCVA gains, independent of CST reductions. TRIAL REGISTRATION: ClinicalTrials.gov ( https://clinicaltrials.gov/ ) identifiers: NCT01363440 and NCT01331681 .
DOI: 10.1038/s41433-022-02058-7
REVIEW
Advanced Retina Implants.
Ophthalmology Retina. 2022 Apr 15
Humayun MS, Lee SY.
Purpose: To discuss the role of advanced retinal implants for retinitis pigmentosa and age-related macular degeneration.
Design: Presented by Mark S Humayun as the Charles Schepen’s Lecture at the Retina Subspecialty Day of the American Academy of Ophthalmology in 2021.
Methods: Review of published literature and clinical trials.
Main Outcome Measures: Visual and anatomical outcomes from retinal implants.
Results: Retinal Implants have been researched over the last few decades and some have been advanced into the clinic. Two types of implants, bioelectronic implants, and stem cell based implants, have shown promising results in restoring some level of vision to patients with inherited retinal degenerations and geographic atrophy. These implants differ in their construction, their location of implantation, and also their safety profile. The results from some of these retinal implants do show that there is a signal of efficacy, and one retinal implant, the Argus II, has been FDA approved.
Conclusions: Careful consideration of the design of the implant and also the associated surgical techniques are necessary to obtain a stable and effective long-term interface between these implants and the retina.
DOI: 10.1016/j.oret.2022.04.009
DIAGNOSIS AND IMAGING
Imaging the Vitreous with a Novel Boosted Optical Coherence Tomography Technique: Posterior Vitreous Detachment.
Retina. 2022 Apr 13.
Spaide RF, Valmaggia P, Maloca PM.
Purpose: To evaluate the anatomic changes in the vitreous associated with evolving posterior vitreous detachment (PVD) over the macula.
Methods: A novel scanning method by which 4 A-scans at each position were averaged prior to the Fourier transform that boosted the image quality sufficiently such that frame averaging could occur. B-scans and volume rendered images of eyes with evidence of any partial separation of the vitreous in the macular regions were evaluated.
Results: There were 43 eyes of 23 subjects with particular attention paid to the findings of 7 eyes with various stages of PVD occurring over the macula. In eyes from young subjects with no vitreous degeneration the outer vitreous showed a diffuse, poorly defined increase in reflectivity in the region where the vitreous cortex was expected to be. In eyes with vitreous degeneration there was a hyperreflective zone, called the cortical vitreous condensation, that coursed parallel to the curvature of the retina. The posterior vitreous face elevated from the retina with either a well-defined, smooth outer surface, consistent with the posterior vitreous membrane or a poorly defined, flocculent outer border. The cortical vitreous near the fovea was thin and in eyes in the process of PVD had visible tears. In more advanced eyes a circular dehiscence of the cortical vitreous in the central macula occurred with herniation of the vitreous gel though the hole.
Conclusions: The methodology produced images of unprecedented clarity that highlighted several newly described details concerning the vitreous changes associated with PVD over the macula.
