Anterior Chamber Angle Anatomy in Non-Glaucomatous Eyes Receiving Repeated Anti-VEGF Injections: A Paired-Eye Cross-Sectional Study

Anterior Chamber Angle Anatomy in Non-Glaucomatous Eyes Receiving Repeated Anti-VEGF Injections: A Paired-Eye Cross-Sectional Study | 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 Anterior Chamber Angle Anatomy in Non-Glaucomatous Eyes Receiving Repeated Anti-VEGF Injections: A Paired-Eye Cross-Sectional Study Zvi Segal, Dana Cohen, Kristina Avanesyan, Valery Bersudsky, Nadav Anteby, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7897246/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background This study aimed to evaluate anterior chamber angle anatomy after multiple intravitreal anti-vascular endothelial growth factor (VEGF) injections for age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO), and to identify associated factors. Methods This cross-sectional paired-eye study included 96 non-glaucomatous patients with unilateral AMD, RVO, or DME receiving repeated intravitreal anti-VEGF injections. Anterior segment optical coherence tomography was used to measure angle parameters in the nasal and temporal quadrants of treated and contralateral untreated eyes. Intraocular pressure (IOP) was measured in both eyes. Quadrant angle parameters and IOP were compared between eyes. Inter-eye difference (treated minus untreated eye) was calculated for quadrant angle parameters and IOP. Associations of inter-eye differences in quadrant angle parameters with inter-eye IOP difference, number of injections, and diagnosis were evaluated using univariate and multivariable analyses. The number of injections in treated eyes was compared between occludable and non-occludable angles. Results Temporal quadrant angle parameters did not differ significantly between treated and untreated eyes (all p > 0.05). Nasal quadrant angle parameters were statistically smaller in treated eyes (all p < 0.05), but the differences were minimal (1.0–2.9%). Mean IOP was significantly higher in treated eyes (p = 0.031). Inter-eye differences in nasal and temporal quadrant angle parameters were not associated with inter-eye IOP difference, number of injections, or diagnosis (all p > 0.05). In treated eyes, the number of injections did not differ significantly between occludable and non-occludable angles (p = 0.237). Conclusions In non-glaucomatous eyes, anterior chamber angle anatomy after multiple intravitreal anti-VEGF injections is not related to the number of injections or the primary retinal diseases managed with this therapy (AMD, RVO, DME).This finding suggests that angle anatomy is unlikely to explain the sustained IOP elevation reported after multiple anti-VEGF injections in previous studies, and that routine gonioscopic monitoring may not be necessary in patients receiving repeated intravitreal anti-VEGF injections. anti-vascular endothelial growth factor (anti-VEGF) injections anterior segment optical coherence tomography (AS-OCT) anterior chamber angle angle opening distances (AOD) trabecular iris space areas (TISA) Background Sustained elevation of intraocular pressure (IOP) has been reported following multiple intravitreal anti–vascular endothelial growth factor (anti-VEGF) injections [ 1 – 5 ]. However, the underlying mechanism remains unclear. Possible explanations include trabeculitis [ 6 ], blockade of the trabecular meshwork by anti-VEGF agents or silicone oil droplets from syringes [ 7 ], and injury to the trabecular meshwork from recurrent transient post-injection IOP elevations [ 8 ]. Single intravitreal anti-VEGF injections have been shown to induce a transient rise in IOP and narrowing of the anterior chamber angle, likely due to increased vitreous pressure [ 9 , 10 ]. Repeated injections may cumulatively elevate vitreous pressure over time, potentially resulting in chronic angle narrowing and sustained IOP elevation. One prior study found no association between the number of anti-VEGF injections and iridocorneal angle width [ 11 ]. However, further investigation is warranted to clarify the role of angle anatomy in eyes treated with multiple injections, which has important clinical implications for determining whether routine gonioscopic monitoring is necessary in patients managed with repeated anti-VEGF therapy. Therefore, in this study we assessed anterior chamber angle anatomy in non-glaucomatous patients receiving repeated anti-VEGF injections for treatment of age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO). Materials and Methods This cross-sectional paired-eye study aimed to assess the anterior chamber angle anatomy after multiple intravitreal anti-VEGF injections. The study was conducted at the Department of Ophthalmology, Galilee Medical Center, Nahariya, Israel, between December 2022 and June 2023. Approval was obtained from the Institutional Ethics Committee (0179-19-NHR), and the study adhered to the tenets of the Declaration of Helsinki. Informed consent was obtained from all patients. Inclusion criteria required the presence of AMD, RVO, or DME in one eye treated with repeated intravitreal anti-VEGF injections, with the contralateral eye unaffected by these conditions and remaining untreated. Patients were eligible only if both eyes were phakic and if the treated eye had received its most recent intravitreal injection within six months prior to enrollment. Exclusion criteria for both eyes included a history of glaucoma, intraocular inflammation, intraocular surgery, trauma, or corneal pathologies that could impede AS-OCT imaging. After recording demographic data, ocular diagnoses (AMD, RVO, DME), and the number of anti-VEGF injections received, all patients underwent anterior segment optical coherence tomography (AS-OCT) imaging followed by IOP measurement to minimize potential imaging artifacts. IOP was measured using Goldmann applanation tonometry, with the average of three readings used for analysis. The inter-eye IOP difference was defined as the IOP of the treated eye minus that of the untreated eye (mmHg). AS-OCT imaging was performed with the ANTERION® system (Heidelberg Engineering Inc., Germany). The Cataract Application was used to measure axial length (AL). The Metrics Application was used to assess anterior chamber angle parameters under light room conditions without pupillary dilation. One ophthalmologist (KA) captured all images, and another (DC), blinded to clinical data, identified scleral spurs. The ANTERION algorithm then calculated the angle parameters. Multiple images were acquired per eye, with only artifact-free scans included for analysis. Angle parameters analyzed included angle opening distances (AOD) and trabecular iris space areas (TISA) at 500 µm and 750 µm from the scleral spur [ 12 ]. Due to poor image quality in the superior and inferior quadrants, the analysis focused on the nasal and temporal quadrants, using scan orientations of 0°–180°, 30°–210°, and 150°–330°. In the right eye, AOD500, AOD750, TISA500 and TISA750 were measured at 0°, 30°, and 330° for the nasal quadrant, and at 150°, 180°, and 210° for the temporal quadrant. In the left eye, this classification was reversed. For each angle parameter, the mean of its values at three distinct locations within the quadrant was calculated and used as the representative value for that quadrant. The difference in angle parameters between eyes (inter-eye difference) was expressed as a percentage difference. For example, the inter-eye difference in AOD500 (ΔAOD500) was calculated as [AOD500 (treated eye)- AOD500 (untreated eye) / AOD500 (untreated eye)] x 100 Statistical Analysis No previous studies have compared AS-OCT angle parameters between both eyes of the same individual. Therefore, sample size estimation was based on a reference study evaluating pre- and post–laser peripheral iridotomy measurements [ 13 ]. That analysis indicated that 12 subjects would be required to detect a significant difference (paired t-test, α = 0.05, power = 90%, Cohen’s d = 1.2). To account for potentially greater inter-eye variability in our study, we increased the target to 50 patients to ensure adequate statistical power. Categorical variables were summarized as frequencies and percentages. Continuous and discrete numerical variables were expressed as mean ± standard deviation with range. Paired t-tests were used to compare axial length, IOP, and quadrant angle parameters (AOD and TISA values) between treated and untreated eyes. Associations between inter-eye differences in quadrant angle parameters and both the number of intravitreal injections and the inter-eye IOP difference were assessed using the Spearman rank correlation coefficient, due to non-parametric data distribution. Multivariable linear regression analysis was performed to assess factors potentially associated with inter-eye differences in AOD750 (ΔAOD750). The Mann–Whitney U test was used to compare the number of injections between occludable and non-occludable quadrants in treated eyes. Statistical analyses were performed using IBM SPSS Statistics (version 29.0), with p-values < 0.05 considered statistically significant. Large language model use To ensure readability upon translation from a non-English-language source, preparation of this article was assisted by ChatGPT (version 5.0, OpenAI, United States), and the final version reviewed by a native English-speaker. Results A total of 96 patients (96 treated eyes and 96 contralateral untreated eyes) were included. Diagnoses in the treated eyes included AMD, RVO, and DME. The mean number of intravitreal injections in the treated eye was 8.9 ± 7.3 (range 3–44). Baseline characteristics are detailed in Table 1 . Table 1 Clinical and ocular characteristics of patients (n = 96) Age (years), mean ± SD (range) 69.13 ± 11.04 (39–95) Female, n (%) Male, n (%) 38 (39.6) 58 (60.4) Treated eyes Diagnosis, n (%) AMD RVO DME Number of injections, mean ± SD / median (range) 49 (51.04) 34 (35.42) 13 (13.54) 8.9 ± 7.3 / 6.5 (3–44) Intra ocular pressure (mmHg), mean ± SD Treated eyes Contralateral untreated eyes p -value 14.16 ± 2.64 13.33 ± 2.6 0.031 Axial length (mm), mean ± SD Treated eyes Contralateral untreated eyes p -value 23.49 ± 0.9 23.56 ± 0.97 0.590 AMD = age-related macular degeneration; RVO = retinal vein occlusion; DME = diabetic macular edema; SD = standard deviation; mm = millimeters; mmHg = millimeters of mercury. The injections received by the treated eyes included bevacizumab, ranibizumab, or aflibercept, with some eyes switching agents during the course of treatment. Each drug was injected via the pars plana using a 30-gauge needle, with a standard injection volume of 0.05 mL The injection site was determined according to the treating physician’s preference. Comparisons of AS-OCT angle parameters by quadrant between treated and untreated eyes were limited to quadrants with complete bilateral data, as a small number of nasal or temporal measurements were missing. In the temporal quadrants, all angle parameters did not differ significantly between treated and untreated eyes (all p > 0.05), with inter-eye percentage differences ranging from 1.2% to 5.4%. In the nasal quadrants, all angle parameters were statistically smaller in treated eyes (all p < 0.05), but the magnitude of inter-eye percentage differences was minimal, ranging from 1.0% to 2.9% (Table 2 ). Table 2 Anterior chamber angle parameters in treated and contralateral untreated eyes (AS-OCT) Parameter Treated eyes mean ± SD Untreated eyes mean ± SD p value Δ mean ± SD AOD 500 nasal mm (n = 92) 0.321 ± 0.138 0.336 ± 0.148 0.048* -1.0 ± 27.0 AOD 750 nasal mm (n = 92) 0.429 ± 0.168 0.45 ± 0.182 0.013* - 1.9 ± 20.5 TISA 500 nasal mm 2 (n = 90) 0.119 ± 0.054 0.126 ± 0.059 0.021* -2.4 ± 28.1 TISA 750 nasal mm 2 (n = 90) 0.210 ± 0.087 0.223 ± 0.095 0.013* -2.9 ± 22.6 AOD 500 temporal mm (n = 93) 0.307 ± 0.135 0.317 ± 0.166 0.178 5.4 ± 36.9 AOD 750 temporal mm (n = 93) 0.415 ± 0.178 0.43 ± 0.211 0.098 1.2 ± 25.3 TISA 500 temporal mm 2 (n = 93) 0.112 ± 0.052 0.116 ± 0.062 0.177 2.4 ± 27.9 TISA 750 temporal mm 2 (n = 93) 0.201 ± 0.089 0.207 ± 0.10 0.210 2.6 ± 27.1 AOD = angle opening distance; TISA = trabecular iris space area; 500 or 750 = distance in µm from the scleral spur; SD = standard deviation; mm = millimeters; mmHg = millimeters of mercury; Δ = inter-eye percent difference, calculated as: $$\:\frac{Mean\:treated\:eye-\:Mean\:untreated\:eye\:}{\:Mean\:untreated\:eye\:}X100\%$$ Values in parentheses indicate the number of angles compared. * Indicate statistical significance in paired t-test (p < 0.05) Table 3 shows that neither the number of injections nor the inter-eye IOP difference were associated with differences in nasal or temporal quadrant angle parameters between treated and untreated eyes. Table 3 Correlations of number of injections and inter-eye IOP difference with differences in nasal and temporal angle parameters between treated and contralateral untreated eyes Parameter Inter-eye difference (Δ) Number of injections r s p IOP Inter-eye difference (mmHg) r s p ΔAOD 500 nasal 0.136 0.197 0.055 0.608 ΔAOD 750 nasal 0.124 0.239 0.175 0.100 ΔTISA 500 nasal 0.060 0.576 0.184 0.089 ΔTISA 750 nasal 0.100 0.350 0.195 0.070 ΔAOD 500 temporal 0.182 0.082 0.054 0.616 ΔAOD 750 temporal 0.149 0.156 0.095 0.375 ΔTISA 500 temporal 0.059 0.573 0.057 0.592 ΔTISA 750 temporal 0.143 0.171 0.100 0.348 Δ = inter-eye percent difference in angle parameters, calculated as: $$\:\frac{Mean\:treated\:eye-\:Mean\:untreated\:eye\:}{\:Mean\:untreated\:eye\:\:}X100\%$$ IOP = intraocular pressure; IOP inter-eye difference = IOP of treated eye – IOP of untreated eye; AOD = angle opening distance; TISA = trabecular iris space area; 500 or 750 = distance in µm from the scleral spur; r s = Spearman correlation coefficient; p = p -value Given the similar behavior of all angle parameters in the association analysis (Table 3 ), AOD750 was selected as the representative parameter for multivariable regression, because it correlates most strongly with gonioscopic narrow angle [ 14 , 15 ]. Results showed that differences in AOD750 (ΔAOD750) between treated and untreated eyes were not significantly associated with the number of injections in either the nasal (B = 0.368, p = 0.253) or temporal (B = − 0.187, p = 0.633) quadrants. Similarly, diagnosis (AMD, RVO, DME) was not significantly associated with ΔAOD750 in either quadrant (all p > 0.05). Other clinical factors, including age and axial length, showed no significant associations (Table 4 ). Table 4 Multivariable linear regression analysis: predictors of inter-eye differences in nasal and temporal AOD750 (ΔAOD750) between treated and contralateral untreated eyes Predictor ΔAOD750 nasal B (SE) p-value ΔAOD750 temporal B (SE) p-value Number of injections 0.368 (0.320) 0.253 -0.187 (0.390) 0.633 Age (years) 0.053 (0.223) 0.811 -0.359 (0.272) 0.191 Gender (male) 3.226 (4.974) 0.518 -0.79 (6.021) 0.896 Axial length (mm) -0.027 (2.793) 0.992 -1.047 (3.391) 0.758 Diagnosis (ref: AMD) DME RVO -1.235 (7.915) -1.350 (5.277) 0.876 0.799 -13.268 (9.381) -0.698 (6.443) 0.161 0.309 AOD750 = angle opening distance at 750 µm from the scleral spur; ΔAOD750 = inter-eye percent difference in AOD750, calculated as: $$\:{\Delta\:}\text{A}\text{O}\text{D}500=\frac{Mean\:AOD500\:\left(treated\:eye\right)-\:Mean\:AOD500\:\left(untreated\:eye\right)}{\:Mean\:AOD500\:\left(untreated\:eye\right)\:}X100\%$$ AMD = age-related macular degeneration; RVO = retinal vein occlusion; DME = diabetic macular edema; mm = millimeters; B = regression coefficient; SE = standard error As a subgroup analysis, only the treated eyes were examined. The nasal and temporal quadrants were classified as occludable or non-occludable, using a TISA500 cut-off of 0.11 mm² [12.16]. Overall, 47% of nasal quadrants and 55% of temporal quadrants were classified as occludable. The number of injections did not differ significantly between occludable and non-occludable quadrants (z = − 0.719, p = 0.237). Discussion This study evaluated anterior chamber angle anatomy following multiple intravitreal anti-VEGF injections in non-glaucomatous patients with unilateral AMD, RVO, or DME. No clinically meaningful differences in angle anatomy were observed between treated and contralateral untreated eyes. Temporal quadrant angle parameters were comparable, while nasal quadrant parameters were statistically smaller in treated eyes; however, the magnitude of these differences (1.0–2.9%) was minimal and unlikely to be clinically relevant. Furthermore, no clinical characteristics were found to be related to differences in angle anatomy between treated and untreated eyes. Inter-eye differences in the angle parameters of the nasal and temporal quadrants were not associated with the number of injections or underlying diagnosis. There was also no correlation between inter-eye differences in IOP and differences in quadrant angle parameters (nasal or temporal) between eyes. Within treated eyes, the number of injections also did not differ between occludable and non-occludable quadrants. Clinically , the absence of an association between anterior chamber angle anatomy and either the number of anti-VEGF injections or the primary retinal diseases treated with this therapy (AMD, RVO, DME is highly relevant. These findings suggest that angle anatomy is unlikely to explain the sustained IOP elevation reported after multiple anti-VEGF injections in previous studies [ 1 – 5 ]. Furthermore, our results support the current clinical practice of not performing routine gonioscopic monitoring in patients receiving repeated intravitreal anti-VEGF injections. Although our study focused on non-glaucomatous patients, this represents the most clinically relevant group, as patients with glaucoma already undergo regular angle assessment as part of their routine management, making additional gonioscopic evaluation unnecessary. Our results complement the findings of O’Bryhim et al. [ 11 ], the only published study to date that has examined anterior chamber angle anatomy in patients receiving repeated anti-VEGF injections. In their cohort of 37 non-glaucomatous AMD patients (61 treated and untreated eyes, mean 9 injections), no association was found between the number of injections and angle width. Because their cohort included both phakic and pseudophakic eyes, and angle width appeared to differ between these groups, lens status may have influenced their results. In contrast, our study included only phakic non-glaucomatous patients, thereby eliminating this potential source of variability. In our larger and more heterogeneous cohort of 96 patients with AMD, RVO, and DME (96 treated and 96 untreated eyes, mean 9 injections), we likewise found that angle anatomy was not associated with the number of injections. Beyond this, we also examined associations with underlying diagnosis, directly compared treated and untreated eyes, and evaluated the number of injections within treated eyes — analyses that were not performed in the study by O’Bryhim et al. This study design provides robust support for our findings. Strengths of our study include the paired-eye design, which allowed direct comparison of angle parameters between treated and untreated eyes of the same patients, thereby strengthening the validity of our findings. In both nasal and temporal quadrants, each angle parameter was measured at three distinct locations, providing a comprehensive assessment of quadrant angle anatomy. All patients were phakic, avoiding confounding from lens status. Injections were uniformly performed with a fixed volume of 0.05 mL, minimizing procedural variability. Finally, inclusion of patients with AMD, RVO, and DME enhances the generalizability of our findings to major retinal diseases treated with anti-VEGF therapy. Several limitations should be acknowledged. The cross-sectional design precludes evaluation of longitudinal changes in angle anatomy over years of treatment. Only the nasal and temporal quadrants were assessed due to limited image quality in the superior and inferior sectors; therefore, potential changes in these quadrants may have been missed, and our study does not represent the entire 360° of the anterior chamber angle. Scleral spur identification was performed manually, although consistently by a single experienced ophthalmologist. While the mean inter-eye IOP difference was statistically significant, the magnitude of this difference was small and may have limited the ability to detect meaningful associations with inter-eye difference in angle parameters. Finally, the exclusion of patients with glaucoma limits the generalizability of our findings to this population; however, this limitation is clinically less relevant, since glaucoma patients routinely undergo gonioscopic evaluation as part of their disease monitoring and management. Conclusions In non-glaucomatous eyes, anterior chamber angle anatomy after multiple intravitreal anti-VEGF injections is not related to the number of injections or the primary retinal diseases managed with this therapy (AMD, RVO, DME).These findings suggest that angle anatomy is unlikely to explain the sustained IOP elevation reported after multiple anti-VEGF injections in previous studies, and that routine gonioscopic monitoring may not be necessary in patients receiving repeated anti-VEGF injections. Longitudinal studies are warranted to validate these results. Abbreviations AL Axial length AMD Age-related macular degeneration Anti-VEGF Anti–vascular endothelial growth factor AOD Angle opening distances AS-OCT Optical coherence tomography DME Diabetic macular edema IOP Intraocular pressure RVO Retinal vein occlusion TISA Trabecular iris space areas Declarations Ethics approval: Approval was obtained from the ethics committee of the Galilee Medical Center in Nahariya, Israel (0179-19-NHR). The procedures used in this study adhere to the tenets of the Declaration of Helsinki. Informed consent was obtained from all individual patients included in the study prior to study activities. Consent for publication: Not applicable. Availability of data and materials: The data sets used and analyzed during the current study are available from the corresponding author upon reasonable request. Competing interests (financial and non-financial): The authors declare that they have no competing interests. Funding: This study was funded by the Israel America Foundation, Inc. (I.A.F). Authors’ contributions : OG conceived and designed the study. KA, DC, and NA acquired the data. OG, ZS and VB analyzed and interpreted the data. OG wrote the manuscript, ZS, DC, and RO reviewed the manuscript critically. All authors read and approved the final manuscript. Acknowledgements: Ossie Sharon, a native English-speaker, reviewed the manuscript for language clarity. References Bakri SJ, McCannel CA, Edwards AO, Moshfeghi DM. Persistent ocular hypertension following intravitreal ranibizumab. Graefes Arch Clin Exp Ophthalmol. 2008;246(7):955–8. https://doi.org/10.1007/s00417-008-0819-2 . Adelman RA, Zheng Q, Mayer H. Persistent ocular hypertension following intravitreal bevacizumab and ranibizumab injections. J Ocul Pharmacol Ther. 2010;26(1):105–10. https://doi.org/10.1089/jop.2009.0076 . Good TJ, Kimura AE, Mandava N, Kahook MY. 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Center","correspondingAuthor":true,"prefix":"","firstName":"Orna","middleName":"","lastName":"Geyer","suffix":""}],"badges":[],"createdAt":"2025-10-19 08:23:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7897246/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7897246/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":96916672,"identity":"c8ae43b4-5eb1-4593-8829-a6dacaa048cc","added_by":"auto","created_at":"2025-11-27 14:08:49","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":76082,"visible":true,"origin":"","legend":"","description":"","filename":"SegalGeyeretal.Manuscript19Oct2025.docx","url":"https://assets-eu.researchsquare.com/files/rs-7897246/v1/de3e646dcd847acd4216eb43.docx"},{"id":96796531,"identity":"df7d707e-a674-4be1-a190-e72e7d85207b","added_by":"auto","created_at":"2025-11-26 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14:20:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":675124,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7897246/v1/c79d0d53-2d28-40c2-8b6a-1f30b7bfce04.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Anterior Chamber Angle Anatomy in Non-Glaucomatous Eyes Receiving Repeated Anti-VEGF Injections: A Paired-Eye Cross-Sectional Study","fulltext":[{"header":"Background","content":"\u003cp\u003eSustained elevation of intraocular pressure (IOP) has been reported following multiple intravitreal anti\u0026ndash;vascular endothelial growth factor (anti-VEGF) injections [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, the underlying mechanism remains unclear. Possible explanations include trabeculitis [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], blockade of the trabecular meshwork by anti-VEGF agents or silicone oil droplets from syringes [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], and injury to the trabecular meshwork from recurrent transient post-injection IOP elevations [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSingle intravitreal anti-VEGF injections have been shown to induce a transient rise in IOP and narrowing of the anterior chamber angle, likely due to increased vitreous pressure [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Repeated injections may cumulatively elevate vitreous pressure over time, potentially resulting in chronic angle narrowing and sustained IOP elevation. One prior study found no association between the number of anti-VEGF injections and iridocorneal angle width [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, further investigation is warranted to clarify the role of angle anatomy in eyes treated with multiple injections, which has important clinical implications for determining whether routine gonioscopic monitoring is necessary in patients managed with repeated anti-VEGF therapy. Therefore, in this study we assessed anterior chamber angle anatomy in non-glaucomatous patients receiving repeated anti-VEGF injections for treatment of age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO).\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis cross-sectional paired-eye study aimed to assess the anterior chamber angle anatomy after multiple intravitreal anti-VEGF injections. The study was conducted at the Department of Ophthalmology, Galilee Medical Center, Nahariya, Israel, between December 2022 and June 2023. Approval was obtained from the Institutional Ethics Committee (0179-19-NHR), and the study adhered to the tenets of the Declaration of Helsinki. Informed consent was obtained from all patients.\u003c/p\u003e\u003cp\u003eInclusion criteria required the presence of AMD, RVO, or DME in one eye treated with repeated intravitreal anti-VEGF injections, with the contralateral eye unaffected by these conditions and remaining untreated. Patients were eligible only if both eyes were phakic and if the treated eye had received its most recent intravitreal injection within six months prior to enrollment. Exclusion criteria for both eyes included a history of glaucoma, intraocular inflammation, intraocular surgery, trauma, or corneal pathologies that could impede AS-OCT imaging.\u003c/p\u003e\u003cp\u003eAfter recording demographic data, ocular diagnoses (AMD, RVO, DME), and the number of anti-VEGF injections received, all patients underwent anterior segment optical coherence tomography (AS-OCT) imaging followed by IOP measurement to minimize potential imaging artifacts. IOP was measured using Goldmann applanation tonometry, with the average of three readings used for analysis. The inter-eye IOP difference was defined as the IOP of the treated eye minus that of the untreated eye (mmHg).\u003c/p\u003e\u003cp\u003eAS-OCT imaging was performed with the ANTERION\u0026reg; system (Heidelberg Engineering Inc., Germany). The Cataract Application was used to measure axial length (AL). The Metrics Application was used to assess anterior chamber angle parameters under light room conditions without pupillary dilation. One ophthalmologist (KA) captured all images, and another (DC), blinded to clinical data, identified scleral spurs. The ANTERION algorithm then calculated the angle parameters. Multiple images were acquired per eye, with only artifact-free scans included for analysis. Angle parameters analyzed included angle opening distances (AOD) and trabecular iris space areas (TISA) at 500 \u0026micro;m and 750 \u0026micro;m from the scleral spur [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Due to poor image quality in the superior and inferior quadrants, the analysis focused on the nasal and temporal quadrants, using scan orientations of 0\u0026deg;\u0026ndash;180\u0026deg;, 30\u0026deg;\u0026ndash;210\u0026deg;, and 150\u0026deg;\u0026ndash;330\u0026deg;. In the right eye, AOD500, AOD750, TISA500 and TISA750 were measured at 0\u0026deg;, 30\u0026deg;, and 330\u0026deg; for the nasal quadrant, and at 150\u0026deg;, 180\u0026deg;, and 210\u0026deg; for the temporal quadrant. In the left eye, this classification was reversed. For each angle parameter, the mean of its values at three distinct locations within the quadrant was calculated and used as the representative value for that quadrant. The difference in angle parameters between eyes (inter-eye difference) was expressed as a percentage difference. For example, the inter-eye difference in AOD500 (ΔAOD500) was calculated as\u003c/p\u003e\u003cp\u003e[AOD500 (treated eye)- AOD500 (untreated eye) / AOD500 (untreated eye)] x 100\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eNo previous studies have compared AS-OCT angle parameters between both eyes of the same individual. Therefore, sample size estimation was based on a reference study evaluating pre- and post\u0026ndash;laser peripheral iridotomy measurements [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. That analysis indicated that 12 subjects would be required to detect a significant difference (paired t-test, α\u0026thinsp;=\u0026thinsp;0.05, power\u0026thinsp;=\u0026thinsp;90%, Cohen\u0026rsquo;s d\u0026thinsp;=\u0026thinsp;1.2). To account for potentially greater inter-eye variability in our study, we increased the target to 50 patients to ensure adequate statistical power.\u003c/p\u003e\u003cp\u003eCategorical variables were summarized as frequencies and percentages. Continuous and discrete numerical variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation with range. Paired t-tests were used to compare axial length, IOP, and quadrant angle parameters (AOD and TISA values) between treated and untreated eyes. Associations between inter-eye differences in quadrant angle parameters and both the number of intravitreal injections and the inter-eye IOP difference were assessed using the Spearman rank correlation coefficient, due to non-parametric data distribution. Multivariable linear regression analysis was performed to assess factors potentially associated with inter-eye differences in AOD750 (ΔAOD750). The Mann\u0026ndash;Whitney U test was used to compare the number of injections between occludable and non-occludable quadrants in treated eyes. Statistical analyses were performed using IBM SPSS Statistics (version 29.0), with p-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered statistically significant.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eLarge language model use\u003c/h3\u003e\n\u003cp\u003eTo ensure readability upon translation from a non-English-language source, preparation of this article was assisted by ChatGPT (version 5.0, OpenAI, United States), and the final version reviewed by a native English-speaker.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 96 patients (96 treated eyes and 96 contralateral untreated eyes) were included. Diagnoses in the treated eyes included AMD, RVO, and DME. The mean number of intravitreal injections in the treated eye was 8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;7.3 (range 3\u0026ndash;44). Baseline characteristics are detailed in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eClinical and ocular characteristics of patients (n\u0026thinsp;=\u0026thinsp;96)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAge (years), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e69.13\u0026thinsp;\u0026plusmn;\u0026thinsp;11.04 (39\u0026ndash;95)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale, n (%)\u003c/p\u003e\n \u003cp\u003eMale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38 (39.6)\u003c/p\u003e\n \u003cp\u003e58 (60.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTreated eyes\u003c/p\u003e\n \u003cp\u003eDiagnosis, n (%)\u003c/p\u003e\n \u003cp\u003eAMD\u003c/p\u003e\n \u003cp\u003eRVO\u003c/p\u003e\n \u003cp\u003eDME\u003c/p\u003e\n \u003cp\u003eNumber of injections, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD / median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e49 (51.04)\u003c/p\u003e\n \u003cp\u003e34 (35.42)\u003c/p\u003e\n \u003cp\u003e13 (13.54)\u003c/p\u003e\n \u003cp\u003e8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;7.3 / 6.5 (3\u0026ndash;44)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntra ocular pressure (mmHg), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003cp\u003eTreated eyes\u003c/p\u003e\n \u003cp\u003eContralateral untreated eyes\u003c/p\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e14.16\u0026thinsp;\u0026plusmn;\u0026thinsp;2.64\u003c/p\u003e\n \u003cp\u003e13.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e\n \u003cp\u003e0.031\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAxial length (mm), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003cp\u003eTreated eyes\u003c/p\u003e\n \u003cp\u003eContralateral untreated eyes\u003c/p\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e23.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e\n \u003cp\u003e23.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003c/p\u003e\n \u003cp\u003e0.590\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eAMD\u0026thinsp;=\u0026thinsp;age-related macular degeneration; RVO\u0026thinsp;=\u0026thinsp;retinal vein occlusion; DME\u0026thinsp;=\u0026thinsp;diabetic macular edema; SD\u0026thinsp;=\u0026thinsp;standard deviation; mm\u0026thinsp;=\u0026thinsp;millimeters; mmHg\u0026thinsp;=\u0026thinsp;millimeters of mercury.\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eThe injections received by the treated eyes included bevacizumab, ranibizumab, or aflibercept, with some eyes switching agents during the course of treatment. Each drug was injected via the pars plana using a 30-gauge needle, with a standard injection volume of 0.05 mL The injection site was determined according to the treating physician\u0026rsquo;s preference.\u003c/p\u003e\n\u003cp\u003eComparisons of AS-OCT angle parameters by quadrant between treated and untreated eyes were limited to quadrants with complete bilateral data, as a small number of nasal or temporal measurements were missing. In the temporal quadrants, all angle parameters did not differ significantly between treated and untreated eyes (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), with inter-eye percentage differences ranging from 1.2% to 5.4%. In the nasal quadrants, all angle parameters were statistically smaller in treated eyes (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), but the magnitude of inter-eye percentage differences was minimal, ranging from 1.0% to 2.9% (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAnterior chamber angle parameters in treated and contralateral untreated eyes (AS-OCT)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eParameter\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTreated eyes\u003c/p\u003e\n \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eUntreated eyes\u003c/p\u003e\n \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026Delta;\u003c/p\u003e\n \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAOD 500 nasal mm\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.321\u0026thinsp;\u0026plusmn;\u0026thinsp;0.138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.336\u0026thinsp;\u0026plusmn;\u0026thinsp;0.148\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.048*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;27.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAOD 750 nasal mm\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.429\u0026thinsp;\u0026plusmn;\u0026thinsp;0.168\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.182\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.013*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;20.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTISA 500 nasal mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.119\u0026thinsp;\u0026plusmn;\u0026thinsp;0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.126\u0026thinsp;\u0026plusmn;\u0026thinsp;0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.021*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;28.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTISA 750 nasal mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.210\u0026thinsp;\u0026plusmn;\u0026thinsp;0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.223\u0026thinsp;\u0026plusmn;\u0026thinsp;0.095\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.013*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;22.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAOD 500 temporal mm\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.307\u0026thinsp;\u0026plusmn;\u0026thinsp;0.135\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.317\u0026thinsp;\u0026plusmn;\u0026thinsp;0.166\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;36.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAOD 750 temporal mm\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.415\u0026thinsp;\u0026plusmn;\u0026thinsp;0.178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.211\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.098\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;25.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTISA 500 temporal mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.112\u0026thinsp;\u0026plusmn;\u0026thinsp;0.052\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.116\u0026thinsp;\u0026plusmn;\u0026thinsp;0.062\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.177\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;27.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTISA 750 temporal mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.201\u0026thinsp;\u0026plusmn;\u0026thinsp;0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.207\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.210\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.6\u0026thinsp;\u0026plusmn;\u0026thinsp;27.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eAOD\u0026thinsp;=\u0026thinsp;angle opening distance; TISA\u0026thinsp;=\u0026thinsp;trabecular iris space area; 500 or 750\u0026thinsp;=\u0026thinsp;distance in \u0026micro;m from the scleral spur; SD\u0026thinsp;=\u0026thinsp;standard deviation; mm\u0026thinsp;=\u0026thinsp;millimeters; mmHg\u0026thinsp;=\u0026thinsp;millimeters of mercury; \u0026Delta;\u0026thinsp;=\u0026thinsp;inter-eye percent difference, calculated as:\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\n \u003cdiv class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e$$\\:\\frac{Mean\\:treated\\:eye-\\:Mean\\:untreated\\:eye\\:}{\\:Mean\\:untreated\\:eye\\:}X100\\%$$\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eValues in parentheses indicate the number of angles compared.\u003c/p\u003e\n \u003cp\u003e* Indicate statistical significance in paired t-test (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05)\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e shows that neither the number of injections nor the inter-eye IOP difference were associated with differences in nasal or temporal quadrant angle parameters between treated and untreated eyes.\u003c/p\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCorrelations of number of injections and inter-eye IOP difference with differences in nasal and temporal angle parameters between treated and contralateral untreated eyes\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 18.7057%;\"\u003e\n \u003cp\u003eParameter\u003c/p\u003e\n \u003cp\u003eInter-eye difference (\u0026Delta;)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\" style=\"width: 16.9629%;\"\u003e\n \u003cp\u003eNumber of injections\u003c/p\u003e\n \u003cp\u003e\u003cem\u003er\u003c/em\u003e\u003csub\u003e\u003cem\u003es\u003c/em\u003e\u003c/sub\u003e \u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\" style=\"width: 18.3014%;\"\u003e\n \u003cp\u003eIOP\u003c/p\u003e\n \u003cp\u003eInter-eye difference (mmHg)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003er\u003c/em\u003e\u003csub\u003e\u003cem\u003es\u003c/em\u003e\u003c/sub\u003e \u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 18.7057%;\"\u003e\n \u003cp\u003e\u0026Delta;AOD 500 nasal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.8549%;\"\u003e\n \u003cp\u003e0.136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.8549%;\"\u003e\n \u003cp\u003e0.197\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 10.2242%;\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.5936%;\"\u003e\n \u003cp\u003e0.608\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 18.7057%;\"\u003e\n \u003cp\u003e\u0026Delta;AOD 750 nasal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.8549%;\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.8549%;\"\u003e\n \u003cp\u003e0.239\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 10.2242%;\"\u003e\n \u003cp\u003e0.175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.5936%;\"\u003e\n \u003cp\u003e0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 18.7057%;\"\u003e\n \u003cp\u003e\u0026Delta;TISA 500 nasal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.8549%;\"\u003e\n \u003cp\u003e0.060\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.8549%;\"\u003e\n \u003cp\u003e0.576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 10.2242%;\"\u003e\n \u003cp\u003e0.184\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.5936%;\"\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 18.7057%;\"\u003e\n \u003cp\u003e\u0026Delta;TISA 750 nasal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.8549%;\"\u003e\n \u003cp\u003e0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.8549%;\"\u003e\n \u003cp\u003e0.350\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 10.2242%;\"\u003e\n \u003cp\u003e0.195\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.5936%;\"\u003e\n \u003cp\u003e0.070\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 18.7057%;\"\u003e\n \u003cp\u003e\u0026Delta;AOD 500 temporal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.8549%;\"\u003e\n \u003cp\u003e0.182\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.8549%;\"\u003e\n \u003cp\u003e0.082\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 10.2242%;\"\u003e\n \u003cp\u003e0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.5936%;\"\u003e\n \u003cp\u003e0.616\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 18.7057%;\"\u003e\n \u003cp\u003e\u0026Delta;AOD 750 temporal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.8549%;\"\u003e\n \u003cp\u003e0.149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.8549%;\"\u003e\n \u003cp\u003e0.156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 10.2242%;\"\u003e\n \u003cp\u003e0.095\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.5936%;\"\u003e\n \u003cp\u003e0.375\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 18.7057%;\"\u003e\n \u003cp\u003e\u0026Delta;TISA 500 temporal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.8549%;\"\u003e\n \u003cp\u003e0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.8549%;\"\u003e\n \u003cp\u003e0.573\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 10.2242%;\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.5936%;\"\u003e\n \u003cp\u003e0.592\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 18.7057%;\"\u003e\n \u003cp\u003e\u0026Delta;TISA 750 temporal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.8549%;\"\u003e\n \u003cp\u003e0.143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.8549%;\"\u003e\n \u003cp\u003e0.171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 10.2242%;\"\u003e\n \u003cp\u003e0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.5936%;\"\u003e\n \u003cp\u003e0.348\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 58.7894%;\"\u003e\u0026Delta;\u0026thinsp;=\u0026thinsp;inter-eye percent difference in angle parameters, calculated as:\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cdiv id=\"Equb\" class=\"Equation\"\u003e\n \u003cdiv class=\"mathdisplay\" id=\"FileID_Equb\" name=\"EquationSource\"\u003e$$\\:\\frac{Mean\\:treated\\:eye-\\:Mean\\:untreated\\:eye\\:}{\\:Mean\\:untreated\\:eye\\:\\:}X100\\%$$\u003c/div\u003e\n\u003c/div\u003e\n\u003cp\u003eIOP\u0026thinsp;=\u0026thinsp;intraocular pressure; IOP inter-eye difference\u0026thinsp;=\u0026thinsp;IOP of treated eye \u0026ndash; IOP of untreated eye;\u003c/p\u003e\n\u003cp\u003eAOD\u0026thinsp;=\u0026thinsp;angle opening distance; TISA\u0026thinsp;=\u0026thinsp;trabecular iris space area; 500 or 750\u0026thinsp;=\u0026thinsp;distance in \u0026micro;m from the scleral spur; r\u003csub\u003es\u003c/sub\u003e = Spearman correlation coefficient; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\n\u003cp\u003eGiven the similar behavior of all angle parameters in the association analysis (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e), AOD750 was selected as the representative parameter for multivariable regression, because it correlates most strongly with gonioscopic narrow angle [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]. Results showed that differences in AOD750 (\u0026Delta;AOD750) between treated and untreated eyes were not significantly associated with the number of injections in either the nasal (B\u0026thinsp;=\u0026thinsp;0.368, p\u0026thinsp;=\u0026thinsp;0.253) or temporal (B = \u0026minus;\u0026thinsp;0.187, p\u0026thinsp;=\u0026thinsp;0.633) quadrants. Similarly, diagnosis (AMD, RVO, DME) was not significantly associated with \u0026Delta;AOD750 in either quadrant (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Other clinical factors, including age and axial length, showed no significant associations (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMultivariable linear regression analysis: predictors of inter-eye differences in nasal and temporal AOD750 (\u0026Delta;AOD750) between treated and contralateral untreated eyes\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePredictor\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026Delta;AOD750 nasal\u003c/p\u003e\n \u003cp\u003eB (SE) p-value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026Delta;AOD750 temporal\u003c/p\u003e\n \u003cp\u003eB (SE) p-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of injections\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.368 (0.320)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.253\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.187 (0.390)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.633\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.053 (0.223)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.811\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.359 (0.272)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.191\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender (male)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.226 (4.974)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.518\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.79 (6.021)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.896\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAxial length (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.027 (2.793)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.992\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.047 (3.391)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.758\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiagnosis (ref: AMD)\u003c/p\u003e\n \u003cp\u003eDME\u003c/p\u003e\n \u003cp\u003eRVO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.235 (7.915)\u003c/p\u003e\n \u003cp\u003e-1.350 (5.277)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.876\u003c/p\u003e\n \u003cp\u003e0.799\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-13.268 (9.381)\u003c/p\u003e\n \u003cp\u003e-0.698 (6.443)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.161\u003c/p\u003e\n \u003cp\u003e0.309\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eAOD750\u0026thinsp;=\u0026thinsp;angle opening distance at 750 \u0026micro;m from the scleral spur; \u0026Delta;AOD750\u0026thinsp;=\u0026thinsp;inter-eye percent difference in AOD750, calculated as:\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cdiv id=\"Equc\" class=\"Equation\"\u003e\n \u003cdiv class=\"mathdisplay\" id=\"FileID_Equc\" name=\"EquationSource\"\u003e$$\\:{\\Delta\\:}\\text{A}\\text{O}\\text{D}500=\\frac{Mean\\:AOD500\\:\\left(treated\\:eye\\right)-\\:Mean\\:AOD500\\:\\left(untreated\\:eye\\right)}{\\:Mean\\:AOD500\\:\\left(untreated\\:eye\\right)\\:}X100\\%$$\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eAMD\u0026thinsp;=\u0026thinsp;age-related macular degeneration; RVO\u0026thinsp;=\u0026thinsp;retinal vein occlusion; DME\u0026thinsp;=\u0026thinsp;diabetic macular edema; mm\u0026thinsp;=\u0026thinsp;millimeters; B\u0026thinsp;=\u0026thinsp;regression coefficient; SE\u0026thinsp;=\u0026thinsp;standard error\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eAs a subgroup analysis, only the treated eyes were examined. The nasal and temporal quadrants were classified as occludable or non-occludable, using a TISA500 cut-off of 0.11 mm\u0026sup2; [12.16]. Overall, 47% of nasal quadrants and 55% of temporal quadrants were classified as occludable. The number of injections did not differ significantly between occludable and non-occludable quadrants (z = \u0026minus;\u0026thinsp;0.719, p\u0026thinsp;=\u0026thinsp;0.237).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study evaluated anterior chamber angle anatomy following multiple intravitreal anti-VEGF injections in non-glaucomatous patients with unilateral AMD, RVO, or DME. No clinically meaningful differences in angle anatomy were observed between treated and contralateral untreated eyes. Temporal quadrant angle parameters were comparable, while nasal quadrant parameters were statistically smaller in treated eyes; however, the magnitude of these differences (1.0\u0026ndash;2.9%) was minimal and unlikely to be clinically relevant. Furthermore, no clinical characteristics were found to be related to differences in angle anatomy between treated and untreated eyes. Inter-eye differences in the angle parameters of the nasal and temporal quadrants were not associated with the number of injections or underlying diagnosis. There was also no correlation between inter-eye differences in IOP and differences in quadrant angle parameters (nasal or temporal) between eyes. Within treated eyes, the number of injections also did not differ between occludable and non-occludable quadrants.\u003c/p\u003e\u003cp\u003e\u003cb\u003eClinically\u003c/b\u003e, the absence of an association between anterior chamber angle anatomy and either the number of anti-VEGF injections or the primary retinal diseases treated with this therapy (AMD, RVO, DME is highly relevant. These findings suggest that angle anatomy is unlikely to explain the sustained IOP elevation reported after multiple anti-VEGF injections in previous studies [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Furthermore, our results support the current clinical practice of not performing routine gonioscopic monitoring in patients receiving repeated intravitreal anti-VEGF injections. Although our study focused on non-glaucomatous patients, this represents the most clinically relevant group, as patients with glaucoma already undergo regular angle assessment as part of their routine management, making additional gonioscopic evaluation unnecessary.\u003c/p\u003e\u003cp\u003eOur results complement the findings of O\u0026rsquo;Bryhim et al. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], the only published study to date that has examined anterior chamber angle anatomy in patients receiving repeated anti-VEGF injections. In their cohort of 37 non-glaucomatous AMD patients (61 treated and untreated eyes, mean 9 injections), no association was found between the number of injections and angle width. Because their cohort included both phakic and pseudophakic eyes, and angle width appeared to differ between these groups, lens status may have influenced their results. In contrast, our study included only phakic non-glaucomatous patients, thereby eliminating this potential source of variability. In our larger and more heterogeneous cohort of 96 patients with AMD, RVO, and DME (96 treated and 96 untreated eyes, mean 9 injections), we likewise found that angle anatomy was not associated with the number of injections. Beyond this, we also examined associations with underlying diagnosis, directly compared treated and untreated eyes, and evaluated the number of injections within treated eyes \u0026mdash; analyses that were not performed in the study by O\u0026rsquo;Bryhim et al. This study design provides robust support for our findings.\u003c/p\u003e\u003cp\u003eStrengths of our study include the paired-eye design, which allowed direct comparison of angle parameters between treated and untreated eyes of the same patients, thereby strengthening the validity of our findings. In both nasal and temporal quadrants, each angle parameter was measured at three distinct locations, providing a comprehensive assessment of quadrant angle anatomy. All patients were phakic, avoiding confounding from lens status. Injections were uniformly performed with a fixed volume of 0.05 mL, minimizing procedural variability. Finally, inclusion of patients with AMD, RVO, and DME enhances the generalizability of our findings to major retinal diseases treated with anti-VEGF therapy.\u003c/p\u003e\u003cp\u003eSeveral limitations should be acknowledged. The cross-sectional design precludes evaluation of longitudinal changes in angle anatomy over years of treatment. Only the nasal and temporal quadrants were assessed due to limited image quality in the superior and inferior sectors; therefore, potential changes in these quadrants may have been missed, and our study does not represent the entire 360\u0026deg; of the anterior chamber angle. Scleral spur identification was performed manually, although consistently by a single experienced ophthalmologist. While the mean inter-eye IOP difference was statistically significant, the magnitude of this difference was small and may have limited the ability to detect meaningful associations with inter-eye difference in angle parameters.\u003c/p\u003e\u003cp\u003eFinally, the exclusion of patients with glaucoma limits the generalizability of our findings to this population; however, this limitation is clinically less relevant, since glaucoma patients routinely undergo gonioscopic evaluation as part of their disease monitoring and management.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn non-glaucomatous eyes, anterior chamber angle anatomy after multiple intravitreal anti-VEGF injections is not related to the number of injections or the primary retinal diseases managed with this therapy (AMD, RVO, DME).These findings suggest that angle anatomy is unlikely to explain the sustained IOP elevation reported after multiple anti-VEGF injections in previous studies, and that routine gonioscopic monitoring may not be necessary in patients receiving repeated anti-VEGF injections. Longitudinal studies are warranted to validate these results.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAL Axial length\u003c/p\u003e\u003cp\u003eAMD Age-related macular degeneration\u003c/p\u003e\u003cp\u003eAnti-VEGF Anti\u0026ndash;vascular endothelial growth factor\u003c/p\u003e\u003cp\u003eAOD Angle opening distances\u003c/p\u003e\u003cp\u003eAS-OCT Optical coherence tomography\u003c/p\u003e\u003cp\u003eDME Diabetic macular edema\u003c/p\u003e\u003cp\u003eIOP Intraocular pressure\u003c/p\u003e\u003cp\u003eRVO Retinal vein occlusion\u003c/p\u003e\u003cp\u003eTISA Trabecular iris space areas\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval:\u0026nbsp;\u003c/strong\u003eApproval was obtained from the ethics committee of the Galilee Medical Center in Nahariya, Israel (0179-19-NHR). The procedures used in this study adhere to the tenets of the Declaration of \u0026nbsp;Helsinki. Informed consent was obtained from all individual patients included in the study prior to study activities.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e The data sets used and analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests (financial and non-financial):\u003c/strong\u003e The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This study was funded by\u0026nbsp;the Israel America Foundation, Inc. (I.A.F).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e: OG conceived and designed the study. KA, DC, and NA acquired the data. OG, ZS and VB analyzed and interpreted the data. OG\u0026nbsp;wrote the manuscript, ZS, DC, and RO reviewed the manuscript critically. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e Ossie Sharon, a native English-speaker, reviewed the manuscript for language clarity.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBakri SJ, McCannel CA, Edwards AO, Moshfeghi DM. Persistent ocular hypertension following intravitreal ranibizumab. Graefes Arch Clin Exp Ophthalmol. 2008;246(7):955\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00417-008-0819-2\u003c/span\u003e\u003cspan address=\"10.1007/s00417-008-0819-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAdelman RA, Zheng Q, Mayer H. 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BMC Ophthalmol. 2021;21:127. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12886-021-01874\u003c/span\u003e\u003cspan address=\"10.1186/s12886-021-01874\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"anti-vascular endothelial growth factor (anti-VEGF) injections, anterior segment optical coherence tomography (AS-OCT), anterior chamber angle, angle opening distances (AOD), trabecular iris space areas (TISA)","lastPublishedDoi":"10.21203/rs.3.rs-7897246/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7897246/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eThis study aimed to evaluate anterior chamber angle anatomy after multiple intravitreal anti-vascular endothelial growth factor (VEGF) injections for age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO), and to identify associated factors.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis cross-sectional paired-eye study included 96 non-glaucomatous patients with unilateral AMD, RVO, or DME receiving repeated intravitreal anti-VEGF injections. Anterior segment optical coherence tomography was used to measure angle parameters in the nasal and temporal quadrants of treated and contralateral untreated eyes. Intraocular pressure (IOP) was measured in both eyes. Quadrant angle parameters and IOP were compared between eyes. Inter-eye difference (treated minus untreated eye) was calculated for quadrant angle parameters and IOP. Associations of inter-eye differences in quadrant angle parameters with inter-eye IOP difference, number of injections, and diagnosis were evaluated using univariate and multivariable analyses. The number of injections in treated eyes was compared between occludable and non-occludable angles.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eTemporal quadrant angle parameters did not differ significantly between treated and untreated eyes (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Nasal quadrant angle parameters were statistically smaller in treated eyes (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), but the differences were minimal (1.0\u0026ndash;2.9%). Mean IOP was significantly higher in treated eyes (p\u0026thinsp;=\u0026thinsp;0.031). Inter-eye differences in nasal and temporal quadrant angle parameters were not associated with inter-eye IOP difference, number of injections, or diagnosis (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In treated eyes, the number of injections did not differ significantly between occludable and non-occludable angles (p\u0026thinsp;=\u0026thinsp;0.237).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eIn non-glaucomatous eyes, anterior chamber angle anatomy after multiple intravitreal anti-VEGF injections is not related to the number of injections or the primary retinal diseases managed with this therapy (AMD, RVO, DME).This finding suggests that angle anatomy is unlikely to explain the sustained IOP elevation reported after multiple anti-VEGF injections in previous studies, and that routine gonioscopic monitoring may not be necessary in patients receiving repeated intravitreal anti-VEGF injections.\u003c/p\u003e","manuscriptTitle":"Anterior Chamber Angle Anatomy in Non-Glaucomatous Eyes Receiving Repeated Anti-VEGF Injections: A Paired-Eye Cross-Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-26 07:40:42","doi":"10.21203/rs.3.rs-7897246/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2025-11-17T06:15:47+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-10-22T09:20:02+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-21T00:50:26+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-21T00:50:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2025-10-19T08:16:18+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4643e575-c762-4982-a77e-0d27a32103d0","owner":[],"postedDate":"November 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-26T07:40:42+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-26 07:40:42","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7897246","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7897246","identity":"rs-7897246","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}