Hamilton, Robin D

Mahroo, Omar A

Preston, Ella

English

UCL Discovery

BRIEF COMMUNICATION OPENExploring regression to the mean in visual acuities byinvestigating measurements at two consecutive time points inuntreated fellow eyesElla Preston1, Robin D. Hamilton1,2 and Omar A. Mahroo 1,2,3✉© The Author(s) 2022Eye; https://doi.org/10.1038/s41433-022-02349-zIn clinical trials and real-world data, eyes with worse baselinevision frequently demonstrate greater visual benefit [1–3]. This canbe attributed to the “ceiling effect” of higher visual acuities (withless room for improvement). Sometimes, an observed decline inacuity in those with better baseline vision is taken to supportearlier intervention. However, “regression to the mean” is alsolikely to contribute: in any measurement having variability(including measurement error or fluctuations in biological state),more extreme initial values are likely, on subsequent measure-ments, to be closer to the mean. We investigated this effect byanalysing visual acuity measurements in untreated fellow eyes.We explored visual acuity measurements in untreated eyes,comparing changes in the top and bottom quintile visual acuitiesat consecutive visits, both forwards and backwards in time.Measurements from patients undergoing unilateral antiVEGFtreatment (for neovascular AMD or for retinal vein occlusionmacular oedema) in the intravitreal injection services of theauthors were included. The retrospective database search covereda 5.5 year period. For each patient, acuities at the first twoconsecutive time points (providing these were ≤90 days) wereincluded, excluding those with visual acuities <10 ETDRS letters ateither visit. Mean acuities for the top 20% and bottom 20% at Visit1 were compared with those at Visit 2. The same was done for thetop and bottom 20% at the second visit (comparing with Visit 1).1375 patients met the inclusion criteria. Mean (SD) intervalbetween visits was 31.0 (7.7) days (ranging from 3 to 89 days).Mean (SD) acuities overall were 74.3 (15.9) and 74.7 (16.1) letters atfirst and second visits respectively. For the top quintile (n= 275) atVisit 1, mean acuity was lower at Visit 2 (mean difference 1.0letters, p < 0.0001); for the bottom quintile at Visit 1, mean visualacuity was higher at Visit 2 (mean difference 2.3 letters,p < 0.0001). For the top quintile at Visit 2, mean acuity was lowerat Visit 1 (mean difference 1.5 letters, p < 0.0001). For the bottomquintile at Visit 2, mean acuity was higher at Visit 1 (meandifference 1.6 letters, p= 0.0039). Figure 1 shows mean acuities byquintile.The phenomenon of regression to the mean was thus observed.In eyes undergoing no intervention, those in the top quintileappeared to lose vision, whilst those in the lowest quintileappeared to gain vision. This was regardless of whether onelooked forwards or backwards in time, and the differenceachieved strong apparent statistical significance. However, theeffect was small (between 1 and 2.3 letters) in our cohort.Nevertheless, we recommend that the phenomenon should beconsidered whenever comparing outcomes in subgroups thathave been stratified by baseline values of the same parameter. Ineyes with active disease, where there is often greater variability orfluctuation in vision, the effect might be greater. The regression tothe mean effect has also been reported in laser refractive surgery[4] and as an explanation for why a simulated switch betweendifferent antiVEGF agents could appear to bring about visual gains[5, 6].DATA AVAILABILITYThe data processed for the analysis in this manuscript are available on request.REFERENCES1. Ying GS, Huang J, Maguire MG, Jaffe GJ, Grunwald JE, Toth C, et al. Baselinepredictors for one-year visual outcomes with ranibizumab or bevacizumab forneovascular age-related macular degeneration. Ophthalmology. 2013;120:122–9.2. Gale R, Pikoula M, Lee AY, Denaxas S, Egan C, Tufail A, et al. Real world evidence on5661 patients treated for macular oedema secondary to branch retinal veinocclusion with intravitreal anti-vascular endothelial growth factor, intravitrealdexamethasone or macular laser. Br J Ophthalmol. 2021;105:549–54.3. Ciulla T, Pollack JS, Williams DF. Visual acuity outcomes and anti-VEGF therapyintensity in macular oedema due to retinal vein occlusion: a real-world analysis of15 613 patient eyes. Br J Ophthalmol. 2021;105:1696–704.4. Aaron MT, Applegate RA, Porter J, Thibos LN, Schallhorn SC, Brunstetter TJ, et al.Why preoperative acuity predicts postoperative acuity in wavefront-guided LASIK.Optom Vis Sci. 2010;87:861–6.5. Ferris FL 3rd, Maguire MG, Glassman AR, Ying GS, Martin DF. Evaluating effects ofswitching anti-vascular endothelial growth factor drugs for age-related maculardegeneration and diabetic macular Edema. JAMA Ophthalmol. 2017;135:145–9.6. Zarbin M, Tsuboi M, Hill LF, Stoilov I. Simulating an anti-vascular endothelialgrowth factor switch in neovascular age-related macular degeneration: A HARBORSubanalysis. Ophthalmology. 2019;126:849–55. https://doi.org/10.1016/j.ophtha.2019.01.003.Received: 7 November 2022 Revised: 14 November 2022 Accepted: 1 December 20221Retinal Service, Moorfields Eye Hospital, London, UK. 2Institute of Ophthalmology, University College London, Bath Street, London, UK. 3Section of Ophthalmology, King’sCollege London, St Thomas’ Hospital Campus, London, UK. ✉email: o.mahroo@ucl.ac.ukwww.nature.com/eye1234567890();,:AUTHOR CONTRIBUTIONSStudy design and conception: OAM. Data collection, analysis and interpretation: allauthors. Drafting manuscript: OAM. Revision: all authors. Approval of final version: allauthors.FUNDINGOAM is funded by the Wellcome Trust (206619_Z_17_Z). The authors acknowledgesupport from the NIHR Biomedical Research Centre at Moorfields Eye Hospital andthe UCL Institute of Ophthalmology. The views expressed in this work are those ofthe authors and not necessarily those of the funding bodies.COMPETING INTERESTSThe authors declare no competing interests.ADDITIONAL INFORMATIONCorrespondence and requests for materials should be addressed to Omar A. Mahroo.Reprints and permission information is available at http://www.nature.com/reprintsPublisher’s note Springer Nature remains neutral with regard to jurisdictional claimsin published maps and institutional affiliations.Open Access This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in anymedium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons licence, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons licence, unlessindicated otherwise in a credit line to the material. If material is not included in thearticle’s Creative Commons licence and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directlyfrom the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.© The Author(s) 2022Fig. 1 Mean visual acuity measurements by quintile in untreated eyes at two consecutive visits. A Points plot mean (±SD) visual acuities ateach visit for each quintile defined by visual acuity at Visit 1. BMean (±SD) visual acuities plotted by quintile as in (A), but quintiles are definedby acuity at Visit 2. The phenomenon of regression to the mean is observed in both cases: for top quintiles at each visit, mean visual acuitywas lower at the other visit; for bottom quintiles at each visit, mean acuity was better at the other visit.E. Preston et al.2Eye

Exploring regression to the mean in visual acuities by investigating measurements at two consecutive time points in untreated fellow eyes

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Exploring regression to the mean in visual acuities by investigating measurements at two consecutive time points in untreated fellow eyes

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