Papillomacular Bundle Thickness is Associated With Visual Acuity in Proliferative Diabetic Retinopathy

Papillomacular Bundle Thickness is Associated With Visual Acuity in Proliferative Diabetic Retinopathy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Papillomacular Bundle Thickness is Associated With Visual Acuity in Proliferative Diabetic Retinopathy Jonathan E. Noonan, Tongalp H. Tezel This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7828739/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: To determine whether the papillomacular bundle thickness (PBT), measured as the retinal nerve fiber layer (RNFL) thickness at a point halfway between the fovea and the optic disc, is significantly associated with best-corrected visual acuity in eyes with proliferative diabetic retinopathy. Methods: A retrospective observational study was conducted on eyes from patients with a history of proliferative diabetic retinopathy in at least one eye who presented to the Ambulatory Care Network (ACN) Vitreoretinal Clinic at New York-Presbyterian Hospital at Columbia University Irving Medical Center between January and December 2023. The PBT was measured using pre-existing Cirrus OCT 512 x 128 macular cube scans. The ETDRS central subfield thickness (CST) was recorded from the Cirrus review software. Best-corrected visual acuity was obtained from the medical record and converted into an ETDRS letter score. Results: Seventy-seven eyes from 45 patients were included. The mean ETDRS letter score, PBT, and CST were 62.1 ± 16.7 letters, 36.1 ± 13.1 μm, and 284.5 ± 90.7 μm, respectively. PBT was significantly correlated with visual acuity (r = 0.40; p < 0.001), while CST was not (p = 0.43). Linear regression analyzing visual acuity as a function of PBT showed a coefficient of 0.51. Conclusions: Thinning of the PBT is associated with decreased visual acuity in eyes with proliferative diabetic retinopathy. Each 1 micrometer of PBT thinning is expected to result in a loss of approximately 0.5 ETDRS letters. ETDRS visual acuity optical coherence tomography papillomacular bundle proliferative diabetic retinopathy retinal nerve fiber layer Figures Figure 1 Figure 2 Key messages The papillomacular bundle carries signals for central visual acuity and is impaired in diseases affecting the optic nerve. In proliferative diabetic retinopathy, thinning of the papillomacular bundle is associated with reduced visual acuity. Central subfield thickness, the average retinal thickness within a 1 mm circle centered on the fovea on optical coherence tomography, was not associated with visual acuity. This is probably because visual acuity is impaired by conditions that both thicken (e.g. diabetic macular edema) and thin (e.g. macular ischemia) the macula. Introduction Vision loss in patients with diabetes can result from any media opacity along the visual pathway, such as cataract or vitreous hemorrhage, center-involving macular edema, macular ischemia, ischemic optic neuropathy, cranial nerve palsies, or vascular issues affecting the upper cortical visual pathways. An important but difficult factor to measure when selecting treatments is the best possible vision the patient can attain. Treatments that may improve vision mainly include intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs or corticosteroids, focal or grid macular laser therapy, and surgery for cataracts, vitreous hemorrhage, or retinal detachment. There is a modest correlation between the thickness at the macular center point and visual acuity in cases of diabetic macular edema [ 1 ]. However, other research has not shown a significant link between visual acuity and the number of optical coherence tomography (OCT)-measured intraretinal hyperreflective foci, intraretinal cysts, or the size of the foveal avascular zone [ 2 – 4 ]. Therefore, additional OCT biomarkers are needed to better assess visual potential and guide treatment decisions. Central visual acuity relies on ganglion cell axons within the papillomacular bundle, which is located in the retinal nerve fiber layer (RNFL) between the fovea and the optic disc [ 5 ]. Damage to this region during vitreoretinal surgery can lead to a central scotoma and reduced visual acuity [ 6 ]. Additionally, thinning of the papillomacular bundle in glaucoma [ 7 – 10 ] and non-arteritic ischemic optic neuropathy [ 11 ] is associated with compromised central vision. In diabetes, retinal ganglion cell death occurs before microangiopathy develops and may cause thinning of the RNFL [ 12 ]. We hypothesized that thinning of the RNFL within the papillomacular bundle would be linked to reduced central visual acuity in patients with type 1 or type 2 diabetes mellitus. To test this, we performed a retrospective observational clinical study of patients with proliferative diabetic retinopathy (PDR) in at least one eye. Methods This cross-sectional retrospective study was approved by the Institutional Review Board at Columbia University, Vagelos College of Physicians and Surgeons (IRB-AAAV0898), and adhered to the principles of the Declaration of Helsinki. Data were collected from patients with type 1 or type 2 diabetes mellitus seen at the Vitreoretinal Clinic of the Ambulatory Care Network at New York-Presbyterian Hospital, Irving Medical Center, Columbia University, spanning January to December 2023. A waiver of consent was granted to review the medical records and OCT data. Participants Patients with proliferative diabetic retinopathy (PDR) in at least one eye were included. Eyes with non-proliferative diabetic retinopathy were included if the fellow eye had PDR. Eyes with macular edema, tractional vitreoretinal pathologies, overt retinal thinning, history of focal macular laser treatment, axial myopia greater than six diopters, glaucoma, compressive or ischemic optic neuropathies, any history of trauma, or other retinal vascular, neurodegenerative, or inflammatory diseases were excluded. Medical records were reviewed for the patient’s age, sex, best-corrected visual acuity, intraocular pressure, type of diabetes mellitus, history of panretinal photocoagulation or vitrectomy, and phakic status. Snellen visual acuities were converted to an ETDRS letter score using a previously described method [ 13 ]. OCT Measurements Cirrus OCT (Carl Zeiss Meditec AG, Germany) 6 x 6 mm macular cube scans were performed using the 512 x 128 protocol. The most recent readable OCT scan was selected for each eye, along with its corresponding medical record entry. Eyes lacking a readable OCT scan that clearly displayed retinal layers were excluded from the analysis. The ETDRS central subfield thickness (CST), which averages the thickness within a 1 mm circle centered on the fovea, was measured with the Cirrus review software. The papillomacular bundle thickness (PBT) was assessed as the RNFL thickness at a point halfway between the fovea and the center of the optic disc on the horizontal scan bisecting the foveola (Fig. 1 ). Statistics Summary statistics and linear regression were performed in RStudio 2024.12.1 Build 563 (Posit Software, PBC, Boston, MA). Data are presented as mean ± standard deviation. A p-value of less than 0.05 was considered statistically significant. Results A total of 77 eyes from 45 patients met the inclusion criteria for this study. The characteristics of the study eyes are detailed in Table 1 . The mean age of the eyes was 58 ± 15 years, and 84% of the eyes belonged to patients with type 2 diabetes. Three eyes (4%) did not have PDR but were included because of PDR in the fellow eye. Panretinal photocoagulation (PRP) and pars plana vitrectomy (PPV) were performed in 83% and 49% of eyes, respectively. Most eyes (56%) were pseudophakic; there were no aphakic eyes in our sample. The mean ETDRS letter score was 62.1 ± 16.7 letters, corresponding to approximately 20/60 Snellen acuity, and the mean intraocular pressure (IOP) was 16.2 ± 3.9 mmHg. The mean (SD) measurements for the PBT and CST were 36.1 ± 13.1 µm and 284.5 ± 90.7 µm, respectively. Table 1 Characteristics of eyes sampled (n = 77 eyes from 45 patients). Age (mean ± SD), years 58 ± 15 Sex (%), male 35 (45%) Laterality (%), right 37 (48%) Diabetes mellitus type 2 (%) 65 (84%) PDR (%) 74 (96%) PRP done (%) 64 (83%) PPV done (%) 38 (49%) Lens Status - Phakic (%) - Pseudophakic (%) - Aphakic (%) - 34 (44%) - 43 (56%) - 0 (0%) ETDRS Visual Acuity 62.1 ± 16.7 letters IOP 16.2 ± 3.9 mmHg PBT 36.1 ± 13.1 mm CST 284.5 ± 90.7 mm CST = central subfield thickness; ETDRS = Early Treatment Diabetic Retinopathy Study; IOP = intraocular pressure; PBT = papillomacular bundle thickness; PDR = proliferative diabetic retinopathy; PPV = pars plana vitrectomy; PRP = panretinal photocoagulation; SD = standard deviation. Scatter plots for PBT and CST, along with the corresponding ETDRS letter score, are shown in Fig. 2 . The correlation coefficient (r) for PBT and visual acuity was 0.40 (P < 0.001), while r for CST and visual acuity was 0.09 (P = 0.43). Linear regression for visual acuity as a function of PBT showed a coefficient of 0.51, with an R² of 0.16. This indicates that for every 1 µm of PBT thinning, there would be an expected 0.5 ETDRS letter decrease in visual acuity. Discussion Our study demonstrated that a decrease in PBT is associated with an expected decline in best-corrected visual acuity in patients with PDR. Specifically, for every 1 micrometer decrease in PBT, there is, on average, a loss of 0.5 ETDRS letters. CST, a more commonly examined OCT marker, was not significantly related to visual acuity. This is probably because the relationship between CST and visual acuity is non-linear. Normal CST values range from 220 to 295 µm according to the Cirrus OCT manual [ 14 ]. Changes outside this normal range, such as central macular thinning caused by retinal ischemia or thickening due to diabetic macular edema, typically result in vision loss. Additional imaging signs that may indicate worse visual prognosis include non-perfusion on retinal angiography or macular thinning and distorted retinal architecture on OCT. Moreover, the chronicity of diabetic maculopathy can lead to neurodegeneration, so even if the edema resolves, central vision might not be restored. PBT has been identified as a biomarker for visual acuity in various eye diseases. In non-arteritic ischemic optic neuropathy, the thickness of the peripapillary retinal nerve fiber layer significantly correlates with visual acuity [ 11 ]. Similarly, in open-angle glaucoma, the PBT measured between the fovea and the optic disc shows a significant relationship with best-corrected visual acuity [ 10 ]. Our findings align with these previous studies, indicating that the connection between PBT and visual acuity extends beyond optic neuropathies to include diabetic retinopathy and potentially other retinal conditions. Additionally, our new method of measuring PBT at the midpoint between the fovea and the optic disc allows this marker to be evaluated using existing Cirrus OCT macular cube scans. The correlation coefficient of 0.4 for PBT and ETDRS visual acuity indicates that PBT has, at best, a modest relationship with visual acuity. Other factors, such as corneal opacification, cataract, vitreous hemorrhage, or a visual pathway lesion, can interfere with a patient’s vision. While measuring the PBT for every patient in the clinic may not be practical, it is relatively easy to qualitatively evaluate the health of the papillomacular bundle using OCT horizontal line scans through the macula. This method could help inform patients about their prognosis and possible treatment responses. The eyes in our study exhibited relatively severe signs of diabetic retinopathy, but no noticeable lesions that might have caused axonal stasis or atrophy. Including such eyes was deliberate, as we did not want any confounding pathology that could have affected the PBT by stasis or atrophy of the nerve fibers. However, retina specialists may encounter diabetic patients with late-stage complications, such as retinal ischemia, macular edema, or tractional detachments, which can impact the estimates of visual potential using our method. Vitreous hemorrhage is another common issue that can prevent the acquisition of quality OCT images. Eyes with more advanced diabetic retinopathy often require more aggressive treatment, although their best possible vision may still be limited. In conclusion, we found that the RNFL thickness at the midpoint between the fovea and the center of the optic nerve (the PBT) is significantly correlated with best-corrected visual acuity in eyes with proliferative diabetic retinopathy. This may help clinicians better understand the visual prognosis for their patients and guide treatment decisions. Further research is needed to determine whether thinning of the PBT is associated with visual acuity before the development of the proliferative stage of diabetic retinopathy. Declarations Financial Support Supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., NYC, NY, and Foley Research Fund, New York, NY (THT); Danny H.-Kauffmann Jokl, MD International Vitreoretinal Fellowship (JEN). Statements and Declarations The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Human Ethics and Consent to Participate declarations This retrospective study was approved and a waiver of consent was obtained from the Institutional Review Board at Columbia University, Vagelos College of Physicians and Surgeons (IRB-AAAV0898). The study adhered to the principles of the Declaration of Helsinki. Author Contribution J.N. designed the study, collected the data and reviewed the manuscript. T.T. provided expert guidance in designing the study and analyzing the data, and reviewed the manuscript. 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Investig Ophthalmol Vis Sci 57:4168–4168 Storch MW, Zinser G, Lauermann P, Khattab MH, Nguyen-Höhl A, Raddatz D, Gollisch K, Callizo J, Hoerauf H, Feltgen N (2022) Influence of the Size of the Foveal Avascular Zone on Functional and Morphological Parameters in Patients with Early-Stage Diabetic Retinopathy. Clin Ophthalmol 16:1207–1213. 10.2147/opth.S358467 Hiraoka M, Inoue K, Kawano H, Takada M (2012) Localization of papillofoveal bundles in primates. Anat Rec (Hoboken) 295:347–354. 10.1002/ar.21519 Pan BX, Yee KM, Ross-Cisneros FN, Sadun AA, Sebag J (2014) Inner Retinal Optic Neuropathy: Vitreomacular Surgery–Associated Disruption of the Inner Retina. Investig Ophthalmol Vis Sci 55:6756–6764. 10.1167/iovs.14-15235 Bak E, Kim M, Kim SH, Lee KM (2024) Optic nerve head factors associated with initial central visual field defect in primary open-angle glaucoma. Sci Rep 14:8000. 10.1038/s41598-024-58749-6 Huh MG, Shin YI, Jeong Y, Kim YK, Jeoung JW, Park KH (2023) Papillomacular bundle defect (PMBD) in glaucoma patients with high myopia: frequency and risk factors. Sci Rep 13:21958. 10.1038/s41598-023-48687-0 Leung CKS, Guo PY, Lam AKN (2022) Retinal Nerve Fiber Layer Optical Texture Analysis: Involvement of the Papillomacular Bundle and Papillofoveal Bundle in Early Glaucoma. Ophthalmology 129:1043–1055. https://doi.org/10.1016/j.ophtha.2022.04.012 Kobayashi W, Kunikata H, Omodaka K, Togashi K, Ryu M, Akiba M, Takeuchi G, Yuasa T, Nakazawa T (2015) Correlation of papillomacular nerve fiber bundle thickness with central visual function in open-angle glaucoma. J Ophthalmol 2015: 460918 10.1155/2015/460918 Rebolleda G, Sánchez-Sánchez C, González-López JJ, Contreras I, Muñoz-Negrete FJ (2015) Papillomacular bundle and inner retinal thicknesses correlate with visual acuity in nonarteritic anterior ischemic optic neuropathy. Invest Ophthalmol Vis Sci 56:682–692. 10.1167/iovs.14-15314 Potilinski MC, Lorenc V, Perisset S, Gallo JE (2020) Mechanisms behind Retinal Ganglion Cell Loss in Diabetes and Therapeutic Approach. Int J Mol Sci 21. 10.3390/ijms21072351 Gregori NZ, Feuer W, Rosenfeld PJ (2010) Novel method for analyzing snellen visual acuity measurements. Retina 30:1046–1050. 10.1097/IAE.0b013e3181d87e04 AG CZM (2017) Cirrus HD-OCT from Zeiss: How to read the reports Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7828739","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":528686935,"identity":"ce989f98-9cd5-4f58-80d8-f844fff54cb4","order_by":0,"name":"Jonathan E. 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Both eyes had undergone tractional retinal detachment repairs.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7828739/v1/58bf2cdc02834c2e514bebbd.png"},{"id":94709396,"identity":"712e5326-d8fb-41dc-b74f-b3ac4af75062","added_by":"auto","created_at":"2025-10-30 01:07:11","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":64210,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plots of PBT versus ETDRS letter scores (A), and CST versus ETDRS letter scores (B). Linear regression lines are overlaid on the data.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7828739/v1/a457c5bb1e95642141ee9f03.png"},{"id":98436010,"identity":"6953e11b-e1d1-4cf8-8c01-6d2ab3210f10","added_by":"auto","created_at":"2025-12-17 16:54:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5113852,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7828739/v1/cff8b20b-8cca-4625-bf3b-cadebd4dbc8d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003ePapillomacular Bundle Thickness is Associated With Visual Acuity in Proliferative Diabetic Retinopathy\u003c/p\u003e","fulltext":[{"header":"Key messages","content":"\u003col\u003e\n \u003cli\u003eThe papillomacular bundle carries signals for central visual acuity and is impaired in diseases affecting the optic nerve.\u003c/li\u003e\n \u003cli\u003eIn proliferative diabetic retinopathy, thinning of the papillomacular bundle is associated with reduced visual acuity.\u003c/li\u003e\n \u003cli\u003eCentral subfield thickness, the average retinal thickness within a 1 mm circle centered on the fovea on optical coherence tomography, was not associated with visual acuity. This is probably because visual acuity is impaired by conditions that both thicken (e.g. diabetic macular edema) and thin (e.g. macular ischemia) the macula.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Introduction","content":"\u003cp\u003eVision loss in patients with diabetes can result from any media opacity along the visual pathway, such as cataract or vitreous hemorrhage, center-involving macular edema, macular ischemia, ischemic optic neuropathy, cranial nerve palsies, or vascular issues affecting the upper cortical visual pathways. An important but difficult factor to measure when selecting treatments is the best possible vision the patient can attain. Treatments that may improve vision mainly include intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs or corticosteroids, focal or grid macular laser therapy, and surgery for cataracts, vitreous hemorrhage, or retinal detachment.\u003c/p\u003e\u003cp\u003eThere is a modest correlation between the thickness at the macular center point and visual acuity in cases of diabetic macular edema [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, other research has not shown a significant link between visual acuity and the number of optical coherence tomography (OCT)-measured intraretinal hyperreflective foci, intraretinal cysts, or the size of the foveal avascular zone [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Therefore, additional OCT biomarkers are needed to better assess visual potential and guide treatment decisions.\u003c/p\u003e\u003cp\u003eCentral visual acuity relies on ganglion cell axons within the papillomacular bundle, which is located in the retinal nerve fiber layer (RNFL) between the fovea and the optic disc [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Damage to this region during vitreoretinal surgery can lead to a central scotoma and reduced visual acuity [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Additionally, thinning of the papillomacular bundle in glaucoma [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and non-arteritic ischemic optic neuropathy [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] is associated with compromised central vision. In diabetes, retinal ganglion cell death occurs before microangiopathy develops and may cause thinning of the RNFL [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eWe hypothesized that thinning of the RNFL within the papillomacular bundle would be linked to reduced central visual acuity in patients with type 1 or type 2 diabetes mellitus. To test this, we performed a retrospective observational clinical study of patients with proliferative diabetic retinopathy (PDR) in at least one eye.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e This cross-sectional retrospective study was approved by the Institutional Review Board at Columbia University, Vagelos College of Physicians and Surgeons (IRB-AAAV0898), and adhered to the principles of the Declaration of Helsinki. Data were collected from patients with type 1 or type 2 diabetes mellitus seen at the Vitreoretinal Clinic of the Ambulatory Care Network at New York-Presbyterian Hospital, Irving Medical Center, Columbia University, spanning January to December 2023. A waiver of consent was granted to review the medical records and OCT data.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eParticipants\u003c/h2\u003e\u003cp\u003ePatients with proliferative diabetic retinopathy (PDR) in at least one eye were included. Eyes with non-proliferative diabetic retinopathy were included if the fellow eye had PDR. Eyes with macular edema, tractional vitreoretinal pathologies, overt retinal thinning, history of focal macular laser treatment, axial myopia greater than six diopters, glaucoma, compressive or ischemic optic neuropathies, any history of trauma, or other retinal vascular, neurodegenerative, or inflammatory diseases were excluded. Medical records were reviewed for the patient\u0026rsquo;s age, sex, best-corrected visual acuity, intraocular pressure, type of diabetes mellitus, history of panretinal photocoagulation or vitrectomy, and phakic status. Snellen visual acuities were converted to an ETDRS letter score using a previously described method [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eOCT Measurements\u003c/h3\u003e\n\u003cp\u003eCirrus OCT (Carl Zeiss Meditec AG, Germany) 6 x 6 mm macular cube scans were performed using the 512 x 128 protocol. The most recent readable OCT scan was selected for each eye, along with its corresponding medical record entry. Eyes lacking a readable OCT scan that clearly displayed retinal layers were excluded from the analysis. The ETDRS central subfield thickness (CST), which averages the thickness within a 1 mm circle centered on the fovea, was measured with the Cirrus review software. The papillomacular bundle thickness (PBT) was assessed as the RNFL thickness at a point halfway between the fovea and the center of the optic disc on the horizontal scan bisecting the foveola (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eStatistics\u003c/h3\u003e\n\u003cp\u003eSummary statistics and linear regression were performed in RStudio 2024.12.1 Build 563 (Posit Software, PBC, Boston, MA). Data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. A p-value of less than 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 77 eyes from 45 patients met the inclusion criteria for this study. The characteristics of the study eyes are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age of the eyes was 58\u0026thinsp;\u0026plusmn;\u0026thinsp;15 years, and 84% of the eyes belonged to patients with type 2 diabetes. Three eyes (4%) did not have PDR but were included because of PDR in the fellow eye. Panretinal photocoagulation (PRP) and pars plana vitrectomy (PPV) were performed in 83% and 49% of eyes, respectively. Most eyes (56%) were pseudophakic; there were no aphakic eyes in our sample. The mean ETDRS letter score was 62.1\u0026thinsp;\u0026plusmn;\u0026thinsp;16.7 letters, corresponding to approximately 20/60 Snellen acuity, and the mean intraocular pressure (IOP) was 16.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9 mmHg. The mean (SD) measurements for the PBT and CST were 36.1\u0026thinsp;\u0026plusmn;\u0026thinsp;13.1 \u0026micro;m and 284.5\u0026thinsp;\u0026plusmn;\u0026thinsp;90.7 \u0026micro;m, respectively.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics of eyes sampled (n\u0026thinsp;=\u0026thinsp;77 eyes from 45 patients).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD), years\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e58\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex (%), male\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35 (45%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLaterality (%), right\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (48%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus type 2 (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65 (84%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePDR (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e74 (96%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePRP done (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e64 (83%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePPV done (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38 (49%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLens Status\u003c/p\u003e\u003cp\u003e- Phakic (%)\u003c/p\u003e\u003cp\u003e- Pseudophakic (%)\u003c/p\u003e\u003cp\u003e- Aphakic (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e- 34 (44%)\u003c/p\u003e\u003cp\u003e- 43 (56%)\u003c/p\u003e\u003cp\u003e- 0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eETDRS Visual Acuity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62.1\u0026thinsp;\u0026plusmn;\u0026thinsp;16.7 letters\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIOP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9 mmHg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePBT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36.1\u0026thinsp;\u0026plusmn;\u0026thinsp;13.1 mm\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e284.5\u0026thinsp;\u0026plusmn;\u0026thinsp;90.7 mm\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eCST\u0026thinsp;=\u0026thinsp;central subfield thickness; ETDRS\u0026thinsp;=\u0026thinsp;Early Treatment Diabetic Retinopathy Study; IOP\u0026thinsp;=\u0026thinsp;intraocular pressure; PBT\u0026thinsp;=\u0026thinsp;papillomacular bundle thickness; PDR\u0026thinsp;=\u0026thinsp;proliferative diabetic retinopathy; PPV\u0026thinsp;=\u0026thinsp;pars plana vitrectomy; PRP\u0026thinsp;=\u0026thinsp;panretinal photocoagulation; SD\u0026thinsp;=\u0026thinsp;standard deviation.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eScatter plots for PBT and CST, along with the corresponding ETDRS letter score, are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The correlation coefficient (r) for PBT and visual acuity was 0.40 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), while r for CST and visual acuity was 0.09 (P\u0026thinsp;=\u0026thinsp;0.43). Linear regression for visual acuity as a function of PBT showed a coefficient of 0.51, with an R\u0026sup2; of 0.16. This indicates that for every 1 \u0026micro;m of PBT thinning, there would be an expected 0.5 ETDRS letter decrease in visual acuity.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study demonstrated that a decrease in PBT is associated with an expected decline in best-corrected visual acuity in patients with PDR. Specifically, for every 1 micrometer decrease in PBT, there is, on average, a loss of 0.5 ETDRS letters. CST, a more commonly examined OCT marker, was not significantly related to visual acuity. This is probably because the relationship between CST and visual acuity is non-linear. Normal CST values range from 220 to 295 \u0026micro;m according to the Cirrus OCT manual [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Changes outside this normal range, such as central macular thinning caused by retinal ischemia or thickening due to diabetic macular edema, typically result in vision loss. Additional imaging signs that may indicate worse visual prognosis include non-perfusion on retinal angiography or macular thinning and distorted retinal architecture on OCT. Moreover, the chronicity of diabetic maculopathy can lead to neurodegeneration, so even if the edema resolves, central vision might not be restored.\u003c/p\u003e\u003cp\u003ePBT has been identified as a biomarker for visual acuity in various eye diseases. In non-arteritic ischemic optic neuropathy, the thickness of the peripapillary retinal nerve fiber layer significantly correlates with visual acuity [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Similarly, in open-angle glaucoma, the PBT measured between the fovea and the optic disc shows a significant relationship with best-corrected visual acuity [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Our findings align with these previous studies, indicating that the connection between PBT and visual acuity extends beyond optic neuropathies to include diabetic retinopathy and potentially other retinal conditions. Additionally, our new method of measuring PBT at the midpoint between the fovea and the optic disc allows this marker to be evaluated using existing Cirrus OCT macular cube scans.\u003c/p\u003e\u003cp\u003eThe correlation coefficient of 0.4 for PBT and ETDRS visual acuity indicates that PBT has, at best, a modest relationship with visual acuity. Other factors, such as corneal opacification, cataract, vitreous hemorrhage, or a visual pathway lesion, can interfere with a patient\u0026rsquo;s vision. While measuring the PBT for every patient in the clinic may not be practical, it is relatively easy to qualitatively evaluate the health of the papillomacular bundle using OCT horizontal line scans through the macula. This method could help inform patients about their prognosis and possible treatment responses.\u003c/p\u003e\u003cp\u003eThe eyes in our study exhibited relatively severe signs of diabetic retinopathy, but no noticeable lesions that might have caused axonal stasis or atrophy. Including such eyes was deliberate, as we did not want any confounding pathology that could have affected the PBT by stasis or atrophy of the nerve fibers. However, retina specialists may encounter diabetic patients with late-stage complications, such as retinal ischemia, macular edema, or tractional detachments, which can impact the estimates of visual potential using our method. Vitreous hemorrhage is another common issue that can prevent the acquisition of quality OCT images. Eyes with more advanced diabetic retinopathy often require more aggressive treatment, although their best possible vision may still be limited.\u003c/p\u003e\u003cp\u003eIn conclusion, we found that the RNFL thickness at the midpoint between the fovea and the center of the optic nerve (the PBT) is significantly correlated with best-corrected visual acuity in eyes with proliferative diabetic retinopathy. This may help clinicians better understand the visual prognosis for their patients and guide treatment decisions. Further research is needed to determine whether thinning of the PBT is associated with visual acuity before the development of the proliferative stage of diabetic retinopathy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eFinancial Support\u003c/h2\u003e\u003cp\u003eSupported in part by an unrestricted grant from Research to Prevent Blindness, Inc., NYC, NY, and Foley Research Fund, New York, NY (THT); Danny H.-Kauffmann Jokl, MD International Vitreoretinal Fellowship (JEN).\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eStatements and Declarations\u003c/strong\u003e\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate declarations\u003c/strong\u003e\u003cp\u003e This retrospective study was approved and a waiver of consent was obtained from the Institutional Review Board at Columbia University, Vagelos College of Physicians and Surgeons (IRB-AAAV0898). The study adhered to the principles of the Declaration of Helsinki.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJ.N. designed the study, collected the data and reviewed the manuscript. T.T. provided expert guidance in designing the study and analyzing the data, and reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBrowning DJ, Glassman AR, Aiello LP, Beck RW, Brown DM, Fong DS, Bressler NM, Danis RP, Kinyoun JL, Nguyen QD, Bhavsar AR, Gottlieb J, Pieramici DJ, Rauser ME, Apte RS, Lim JI, Miskala PH (2007) Relationship between optical coherence tomography-measured central retinal thickness and visual acuity in diabetic macular edema. 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Retina 30:1046\u0026ndash;1050. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/IAE.0b013e3181d87e04\u003c/span\u003e\u003cspan address=\"10.1097/IAE.0b013e3181d87e04\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAG CZM (2017) Cirrus HD-OCT from Zeiss: How to read the reports\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"ETDRS visual acuity, optical coherence tomography, papillomacular bundle, proliferative diabetic retinopathy, retinal nerve fiber layer","lastPublishedDoi":"10.21203/rs.3.rs-7828739/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7828739/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eTo determine whether the papillomacular bundle thickness (PBT), measured as the retinal nerve fiber layer (RNFL) thickness at a point halfway between the fovea and the optic disc, is significantly associated with best-corrected visual acuity in eyes with proliferative diabetic retinopathy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA retrospective observational study was conducted on eyes from patients with a history of proliferative diabetic retinopathy in at least one eye who presented to the Ambulatory Care Network (ACN) Vitreoretinal Clinic at New York-Presbyterian Hospital at Columbia University Irving Medical Center between January and December 2023. The PBT was measured using pre-existing Cirrus OCT 512 x 128 macular cube scans. The ETDRS central subfield thickness (CST) was recorded from the Cirrus review software. Best-corrected visual acuity was obtained from the medical record and converted into an ETDRS letter score.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eSeventy-seven eyes from 45 patients were included. The mean ETDRS letter score, PBT, and CST were 62.1 ± 16.7 letters, 36.1 ± 13.1 μm, and 284.5 ± 90.7 μm, respectively. PBT was significantly correlated with visual acuity (r = 0.40; p \u0026lt; 0.001), while CST was not (p = 0.43). Linear regression analyzing visual acuity as a function of PBT showed a coefficient of 0.51.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eThinning of the PBT is associated with decreased visual acuity in eyes with proliferative diabetic retinopathy. Each 1 micrometer of PBT thinning is expected to result in a loss of approximately 0.5 ETDRS letters.\u003c/p\u003e","manuscriptTitle":"Papillomacular Bundle Thickness is Associated With Visual Acuity in Proliferative Diabetic Retinopathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-30 01:07:06","doi":"10.21203/rs.3.rs-7828739/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0873856d-e8b6-4718-a08a-69988ea81f36","owner":[],"postedDate":"October 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-02T09:27:34+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-30 01:07:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7828739","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7828739","identity":"rs-7828739","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}