Retinal and Optic-Disc Changes Associated With ¹³¹I Therapy in Papillary Thyroid Carcinoma and Their Determinants

Authors: Yan-Jie Li, Ding Hu, Hai-Tao Feng, Zeng-Yu Zhang, Zi-Ai Yang, Yi-Xin Wang, Tian-Yue Liu, Si-Jin Li, Hai-Yan Liu

Abstract

Purpose

This study aimed to evaluate retinal and optic-disc changes in papillary thyroid carcinoma (PTC) following post-surgical radioactive iodine (¹³¹I) therapy and identify the factors influencing these changes.

Methods

This study enrolled 60 patients (120 eyes) who received ¹³¹I therapy after surgical removal of PTC. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) were used to evaluate the macular and optic-disc structures, and macular microcirculation before and 1 month after ¹³¹I therapy. The effects of ¹³¹I dose and pretreatment lymphocyte-subset levels on the differences were analyzed.

Results

The superior outer ring of the macular region was thinner after ¹³¹I therapy than before (P < 0.05). The cup-to-disc ratio (CDR) was slightly increased (P < 0.001), whereas the thicknesses of the ganglion cell layer and retinal nerve fiber layer showed no significant changes (P > 0.05). Vessel density (VD) and perfusion density (PD) in the superficial choroidal vascular plexus were decreased (P < 0.05), especially in patients with high B-lymphocyte levels (P < 0.05). The VD and PD of the inner ring, outer ring, whole circle, and several sectoral regions decreased more in the 150 to 200 millicurie (mCi) group than in the <150 and >200 mCi groups. No significant linear associations were found among ¹³¹I dosage, baseline B-lymphocyte levels, age, or body mass index (BMI) and retinal microvascular changes (all P > 0.05).

Conclusions

After initial ¹³¹I therapy, patients with PTC exhibit short-term macular thinning, reduced blood flow, and a slight CDR increase, highlighting the need to monitor optic-disc changes. The ¹³¹I dosage and pretreatment B-lymphocyte levels may be associated with post-therapy retinal microcirculation; however, the relationship does not appear to follow a simple linear pattern.

Over the past few decades, the global incidence of thyroid cancer has shown a consistent upward trend,^1^^,^^2^ with papillary thyroid carcinoma (PTC) being the most common type.^3^ In particular, the incidence of PTC in China has rapidly risen in recent years.^3^ As research advances, increasing evidence suggests that thyroid cancer affects the retinal structure.^4^ The standard treatment, radioactive iodine (¹³¹I) therapy, produces favorable outcomes in most patients with PTC.^5^ However, ¹³¹I therapy can destroy residual thyroid tissue, triggering an inflammatory response accompanied by the release of inflammation-related serum biomarkers.^6^^–^^8^ These inflammatory mediators may subsequently damage retinal vascular endothelial cells, disrupting retinal vascular homeostasis.^9^ Therefore, investigating changes in retinal structure and microcirculation before and after ¹³¹I therapy is essential for understanding the potential ocular side effects of this treatment.

Inflammatory mediators, oxidative damage, and metabolic dysregulation are increasingly recognized as major risk factors for damage to ocular structures, including the retina, optic nerve, and optic disc.^10^^,^^11^ These tissue structures are highly sensitive to microvascular regulatory disorders and metabolic imbalances.^12^^,^^13^ Previous studies suggest that ¹³¹I can increase the expression of NADPH oxidase (NOX)1 in thyroid tissue, leading to the production of a large amount of reactive oxygen species (ROS) and inducing systemic oxidative stress. In addition, thinning of the retinal inner and photoreceptor layers, along with alterations in the optic disc cup-to-disc ratio (CDR), may be closely associated with the inflammatory response, oxidative damage, and metabolic dysregulation induced by ¹³¹I therapy.^14^^,^^15^ These systemic reactions may have sustained effects on ocular tissues, leading to progressive damage to the retina and optic disc. The ocular implications of thyroid diseases have attracted considerable research attention, including studies on thyroid-associated ophthalmopathy, Graves’ ophthalmopathy, and the potential link between thyroid cancer and age-related macular degeneration.^16^^–^^18^ However, quantitative analyses of retinal and optic disc structure and blood flow following ¹³¹I therapy for PTC remain limited. In particular, there is currently a lack of systematic evaluation on whether ¹³¹I treatment can induce subclinical changes in the structure and blood flow of the retina or optic disc. Therefore, further investigation is needed to determine whether ¹³¹I therapy affects the retina and optic disc in patients with PTC.

Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) are advanced, noninvasive in vivo retinal imaging techniques. Through computer-assisted analysis, these technologies enable layered visualization of retinal anatomical structures, such as the photoreceptor tissue, and simultaneously capture dynamic blood-perfusion information. This capability provides critical support for the early diagnosis, follow-up, and prognostic assessment of retinal disorders. Therefore, this study aimed to quantitatively evaluate the structural changes in the retina and optic disc, as well as alterations in microcirculatory blood flow, in patients with PTC following ¹³¹I therapy using OCT and OCTA. Furthermore, it sought to examine the relationship between these changes and both the administered ¹³¹I dose and pretreatment lymphocyte-subset levels.

Methods

Study Cohort

This prospective study was conducted from April 2024 to July 2025 in the Departments of Ophthalmology and Nuclear Medicine at the First Hospital of Shanxi Medical University. The study adhered to the principles of the Declaration of Helsinki for research involving human subjects and was approved by the Ethics Committee of the First Hospital of Shanxi Medical University (No: KYLL-2023-198).

Inclusion criteria were as (1) pathologically confirmed PTC following thyroid cancer surgery, (2) no prior ¹³¹I therapy, and (3) blood pressure and fasting blood-glucose levels within physiological ranges (systolic <120 millimeters of mercury [mm Hg], diastolic <80 mm Hg; fasting glucose, 3.9–6.1 mmol/L).

Exclusion criteria were (1) inability to undergo examination due to poor vision, nystagmus, or refractive media opacity, (2) optic nerve or vitreoretinal disease, (3) history of ocular trauma or surgery, (4) history of uveitis, (5) use of medications affecting retinal microcirculation, such as hydroxychloroquine, (6) autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus, and (7) history of smoking and drinking.

The patient selection process is illustrated in Figure 1^2^. A total of 60 patients (120 eyes) were enrolled, comprising 12 men (24 eyes) and 48 women (96 eyes).

General Examination

• (1)Collection of personal information, including information about gender, age, alcohol and smoking habits, and history of diabetes or hypertension.
• (2)Measurement of best-corrected visual acuity (BCVA) using the international standard logarithmic visual acuity chart (converted to logMAR) and intraocular pressure (IOP). Examination with a slit-lamp microscope was conducted to rule out cataract surgery, ocular trauma, uveitis, and other potential ocular diseases.

Laboratory Measurements

Thyroid function tests include free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), anti-thyroid peroxidase antibodies (TPOAb), anti-thyroglobulin antibodies (TgAb), parathyroid hormone (PTH), and 25-(OH)VD. All tests are performed using automated biochemical analyzers in our institution’s clinical laboratory. Blood samples are collected at two time prior to ¹³¹I therapy and 1-month post-treatment.

Lymphocyte Subset Analysis

Peripheral blood lymphocyte subsets were measured before ¹³¹I therapy using flow cytometry as part of routine pretreatment assessment. The analyzed subsets included total lymphocytes, T lymphocytes, B lymphocytes, natural killer (NK) cells, CD4^+^ T cells, and CD8^+^ T cells.

Based on the reference ranges provided by the clinical laboratory of our institution, patients were categorized into low, normal, or high groups for each lymphocyte subset. All lymphocyte measurements used for grouping were obtained before ¹³¹I therapy. These predefined groupings were applied for subsequent subgroup analyses of retinal structural and microcirculatory changes.

Pathological Biopsy Results

Following PTC surgery, biopsy was performed to determine tumor type, lymph node metastasis, and invasion of peripheral tissues (including the fibrous capsule, adipose tissue, intravascular cancer thrombus, nerves, and muscles) to guide the selection of ¹³¹I dosage.

OCT and OCTA Imaging

All the participants underwent OCT and OCTA imaging using the Cirrus HD-OCT 5000 Review Software V.10 (Carl Zeiss Meditec GmbH, Jena, Germany) both before and 1 month after ¹³¹I therapy.(1)The macula was segmented according to the Early Treatment Diabetic Retinopathy Study protocol into the central circle (0–1 mm), inner ring (1–3 mm), outer ring (3–6 mm), and entire circle (0–6 mm). The inner and outer rings were further subdivided into four superior, inferior, nasal, and temporal (Fig. 2).(2)The retinal nerve fiber layer (RNFL) was divided into the following four superior, inferior, nasal, and temporal. RNFL thickness was measured using the Optic Disc Cube 200 × 200 program, and the CDR was calculated.(3)Macular thickness (inner limiting membrane [ILM] to retinal pigment epithelium [RPE]) and ganglion cell layer (GCL) thickness were measured using the Macular Cube 512 × 128 program. Final calculations were performed using the OU analysis mode.(4)OCTA examination of the macular region was performed using the Angiography 6 × 6 mm program. Vessel density (VD) and perfusion density (PD) were calculated using the built-in angiography analysis mode (FORUM platform, Carl Zeiss Meditec Inc.) and the Optical Micro-angiography algorithm. Macular thickness was defined as ILM–RPE thickness.

OCTA measurements in this study were limited to the superficial retinal vascular plexus. Parameters of the deep retinal vascular plexus were not included in the analysis.

Statistical Analysis

All the statistical analyses were performed using IBM SPSS Statistics 27 (IBM Corporation, Armonk, NY, USA). Baseline characteristics are presented as mean ± SD for continuous variables and as frequency and percentage for categorical variables. Continuous variables were assessed for normality. Variables meeting normality assumptions were analyzed using independent samples t-tests or ANOVA, whereas non-normally distributed variables were analyzed using nonparametric tests.

For ophthalmic parameters, post-treatment changes were calculated as the difference between measurements obtained after and before ¹³¹I therapy (Δ = before - after). Because both eyes from the same participant were included in the analysis, generalized estimating equation (GEE) models account for inter-eye correlation. In addition, multivariate analysis using GEE was performed to assess the association between clinical variables and retinal microvascular changes. P < 0.05 was considered to indicate statistical significance.

Results

Baseline Characteristics of the Participants

This study included 60 patients (120 eyes), with a mean age of 40.94 ± 12.27 years (range = 17–75 years) and a mean body mass index (BMI) of 25.06 ± 3.81. The cohort included 12 men (20.00%) and 48 women (80.00%). The ¹³¹I therapy dose was <150 millicurie (mCi) in 22 patients (36.67%), 150 to 200 mCi in 24 patients (40.00%), and ≥200 mCi in 14 patients (23.33%; Table 1).

Changes in BCVA and IOP in Patients With PTC Following ^131^I Therapy

BCVA and IOP did not significantly change in patients with PTC following ¹³¹I therapy (P > 0.05; Table 2).

Changes in Thyroid-Hormone Levels in Patients With PTC Following ^131^I Therapy

Patients exhibited upregulation of free triiodothyronine and free thyroxine (P < 0.001), and downregulation of thyroid-stimulating hormone following ¹³¹I therapy, compared with pretherapy levels (P < 0.001; Table 3).

Ophthalmic Changes in Patients With PTC Following ^131^I Therapy

Macular thickness in the area above the outer ring was lower following ¹³¹I therapy, compared with pretherapy levels (P < 0.05), whereas GCL thickness showed no statistically significant change (P > 0.05) (Table 4; Figs. 3a, 3b, 4a).

Parameters of macular blood flow showed a decreasing trend following ¹³¹I therapy, compared with pretherapy levels. Significant reductions in PD and VD were observed in the inner ring, outer ring, and whole circle (P < 0.05; Table 5; Figs. 3c, 3d, 4d, 4e). Quadrant analysis revealed significant decreases in VD in the inferior and temporal quadrants of the macular inner ring, the superior, nasal, and temporal quadrants of the macular outer ring, as well as in the PD in the inferior of the macular inner ring, and the superior, nasal, and temporal quadrants of the macular outer ring (P < 0.05; see Table 5; Figs. 3c, 3d, 4b, 4c).

Following ¹³¹I therapy, patients exhibited a slight but statistically significant increase in the CDR, compared with pretherapy levels (P < 0.05). No significant difference was observed in RNFL thickness across any quadrant (P > 0.05; Table 6; Figs. 3e, 3f).

Effects of ^131^I Dose on Ophthalmic Parameters in Patients With PTC

VD differed significantly across dose groups in the macular inner ring, outer ring, whole circle, and several sectoral regions, including the temporal quadrant of the macular inner ring, the superior, inferior, and temporal quadrants of the macular outer ring (P < 0.05). Similarly, PD showed significant dose-group differences in the macular outer ring, whole circle, and selected inner and outer ring sectors, including the temporal of the macular inner ring, the superior, inferior, and temporal quadrants of the macular outer ring (P < 0.05). In contrast, no significant differences were detected in macular thickness, GCL, optic-disc parameters, or RNFL thickness among the different ¹³¹I dose groups (P > 0.05; Supplementary Table S1).

Influences of Lymphocyte Subsets on Ophthalmic Changes Induced by ^131^I Therapy

Before ¹³¹I therapy, levels of total lymphocytes and lymphocyte subsets (natural killer, T and B cells, as well as CD4⁺ T and CD8⁺ T subsets) of the patients were categorized as low, normal, or high based on their respective normal ranges. Subsequently, the retinal and optic-disc structures and macular microcirculation of each patient were assessed.

Results showed that, compared with patients with normal lymphocyte levels, those with low lymphocyte levels exhibited more pronounced thinning of the fovea, the superior, the inferior macular thickness in the inner ring and the inferior macular thickness in the outer ring following ¹³¹I therapy (P < 0.05). Additionally, patients with low CD4⁺ T lymphocyte levels showed greater thinning of the inferior and nasal macular thickness in the inner ring (P < 0.05; Supplementary Table S2).

The impact of B-lymphocyte levels on macular blood flow parameters was particularly notable. Compared with patients with low B-lymphocyte levels, those with high levels showed significantly greater reductions in VD in the superior, inferior, nasal, and outer regions of the macular outer ring, the nasal of the macular inner ring, as well as across the entire macular circle following ¹³¹I therapy (P < 0.05; see Supplementary Table S2; Fig. 5a). Additionally, patients with high B-lymphocyte levels experienced more pronounced decreases in PD in the outer, and entire arcades after ¹³¹I therapy (P < 0.05; Supplementary Table S3; Fig. 5b).

Multivariate Analysis of Factors Associated With Retinal Microvascular Changes

Multivariate GEE analysis, including ¹³¹I dosage, age, baseline B-lymphocyte levels, and BMI, did not identify significant independent associations with ΔVD or ΔPD in the whole macular region (all P > 0.05; Supplementary Table S4). These findings suggest that no simple linear relationships were observed, despite the group-based differences described above.

Discussion

To date, few studies have investigated the effects of ¹³¹I therapy on retinal structure and microcirculation in patients with PTC. Most prior studies have focused on the impact of ¹³¹I on thyroid or lacrimal gland function.^19^^–^^22^ In this context, the present study evaluated changes in retinal and optic-disc structures and macular microcirculation in patients with PTC following ¹³¹I therapy, aiming to identify potential effects of ¹³¹I on retinal architecture and microcirculation.

Although no significant changes in BCVA or IOP were observed following ¹³¹I therapy, the lack of difference likely reflects the longer time frame required for alterations in visual function. Nevertheless, retinal thickness in the region above the outer macular ring decreased following ¹³¹I therapy compared with pretreatment measurements. Previous studies have shown that ¹³¹I therapy can induce systemic inflammatory responses. Demir et al.^7^ have reported significant increases in the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with differentiated thyroid carcinoma after ¹³¹I therapy. Other studies have demonstrated a negative correlation between platelet-to-lymphocyte ratio and retinal thickness.^4^ These findings support the hypothesis that the thinning of macular thickness in patients with PTC following ¹³¹I therapy may result from systemic inflammation, with the persistent inflammatory response progressively damaging the retina.^9^^,^^11^^,^^23^

In the present study, retinal microvascular changes appeared to be more prominent than structural alterations during the short-term follow-up after ¹³¹I therapy. VD and PD in the superficial macular vascular plexus showed a decreasing trend, particularly in the inner and outer macular rings, whereas structural changes were more limited. Among the structural parameters, only the superior outer macular thickness showed a significant reduction after therapy, whereas no consistent changes were observed in GCL thickness or RNFL thickness. This pattern is biologically plausible, as OCTA is highly sensitive to early microcirculatory impairment and may detect vascular dysfunction before more widespread structural damage becomes evident.^24^ From a pathophysiological perspective, these findings are more likely related to indirect systemic effects of ^131^I therapy. Radioiodine treatment has been reported to induce inflammatory activation and immune alterations,^6^^–^^8^ as well as oxidative stress responses that may impair vascular endothelial function and disrupt retinal microvascular homeostasis.^23^ In addition, rapid endocrine fluctuations following therapy may further influence retinal metabolism and vascular autoregulation may further influence retinal metabolism and vascular autoregulation, likely through transient alterations in endothelial function and microvascular regulation associated with thyroid hormone imbalance.^25^^–^^27^ Under these conditions, the retinal microvasculature may be affected earlier and more diffusely, whereas structural changes may remain subtle and regionally restricted in the short term.

When evaluating the relationship between ¹³¹I dosage and retinal changes, group-based analyses revealed significant differences in VD and PD across dose categories in multiple macular regions, whereas multivariate and correlation analyses did not demonstrate significant linear associations. These findings suggest that the dose–response relationship may not follow a simple monotonic pattern. This apparent discrepancy likely reflects the complexity of systemic radioiodine effects. Unlike localized ocular radiotherapy, systemic ¹³¹I therapy does not result in uniform or directly quantifiable radiation delivery to retinal tissue. Instead, retinal responses may be influenced by multiple interacting factors, including individual immune-inflammatory status, systemic metabolic changes, and regional retinal susceptibility, leading to heterogeneous and nonlinear microvascular responses. Some indirect contextual evidence may be drawn from studies of radiation-related ocular changes in other settings. OCTA studies in eyes treated with ^125^I plaque brachytherapy for uveal melanoma have demonstrated reduced macular and peripapillary capillary perfusion and vascular density, particularly in association with radiation retinopathy or macular lesions.^28^ Longitudinal studies further suggest that microvascular alterations may precede clinically detectable structural changes.^29^ However, these findings should be interpreted with caution. Unlike ^125^I plaque brachytherapy, which delivers high-dose focal radiation directly to ocular tissues, systemic ¹³¹I therapy results in relatively low and diffuse radiation exposure to the eye. Therefore, findings from localized ocular radiotherapy cannot be directly extrapolated to systemic ¹³¹I therapy. Nevertheless, these studies may provide useful conceptual insights into the early vulnerability of retinal microvasculature in radiation-related injury.

In addition to indirect systemic effects, a potential contribution of direct retinal toxicity from ¹³¹I cannot be entirely excluded, although direct clinical evidence remains limited. Experimental and clinical observations suggest that iodine-related compounds may accumulate in ocular tissues, particularly in the RPE and choroid,^30^^,^^31^ where they may induce cellular stress and structural damage. Case reports have described retinal abnormalities and choroidal hemorrhage following excessive iodine exposure, with imaging findings indicating disruption at the RPE level.^32^ Animal studies further support this notion, demonstrating the presence of ¹³¹I within ocular tissues after systemic administration, along with structural damage to photoreceptor and RPE cells.^33^^,^^34^ Experimental models have also shown that iodate-induced retinal injury involves multiple pathways, including oxidative stress and both caspase-dependent and caspase-independent cell death mechanisms.^35^^,^^36^ However, it is important to note that most of these findings are derived from conditions involving high-dose or direct iodine exposure, which differ substantially from the relatively low and diffuse radiation exposure associated with systemic ¹³¹I therapy. Therefore, whereas direct retinal toxicity may represent a possible contributory mechanism, the retinal changes observed in the present study are more likely to be primarily driven by indirect systemic processes. This interpretation is also consistent with the nonlinear dose–response pattern observed in this study.

We also incorporated lymphocyte subsets into our analysis, revealing that baseline lymphocyte status correlates with macular structural changes following ¹³¹I therapy. Specifically, patients with lower lymphocyte levels exhibited significantly reduced macular thickness compared with those in the healthy lymphocyte group. Furthermore, individuals with low CD4⁺ T cell levels demonstrated more pronounced thinning in the inferior of the macular inner ring relative to those with normal CD4⁺ T cell levels. These findings suggest that pretreatment immune status may be associated with early subclinical macular thinning following ^131^I therapy. This interpretation is supported by prior evidence linking lymphocyte subsets to retinal structure and microcirculation. For instance, Li et al.^4^ reported correlations between lymphocyte counts (including CD4⁺ T cells) and retinal thickness, indicating that reduced lymphocyte levels may accompany retinal measurements of thinning. Adina et al.^37^ indicated that ¹³¹I therapy is also associated with decreased peripheral lymphocyte levels, suggesting potential immune dysregulation before and after treatment. Therefore, we propose that patients with lower baseline lymphocyte levels may be more susceptible to treatment-related systemic stressors—such as inflammatory or oxidative responses—which could lead to early macular structural alterations.

In the analysis of lymphocyte subsets, B lymphocyte levels appear to be closely associated with VD and PD. Patients with elevated B lymphocyte levels exhibited significantly reduced macular vascular density and perfusion density across multiple regions, particularly in the outer macular ring and the entire macular area. These findings suggest that pretreatment B lymphocyte levels may influence retinal microcirculation following ¹³¹I therapy. Previous studies support the association between B lymphocyte-mediated immune activity and retinal microcirculation. Rheumatoid arthritis, a prototypical autoimmune disease characterized by elevated B-cell levels during inflammatory progression,^38^^,^^39^ is associated with markedly reduced superficial retinal vascular density and capillary perfusion compared with healthy controls.^40^^,^^41^ Similarly, studies in patients with uveitis demonstrate enhanced B-cell immune responses in peripheral blood and ocular fluids, accompanied by widespread reductions in retinal capillary density and vascular complexity.^42^^,^^43^ Mechanistically, B lymphocytes may exacerbate retinal microvascular injury through multiple pathways, including promoting T-cell activation, increasing immunoglobulin and proinflammatory cytokine production. Experimental evidence further supports this notion, as animal models of ocular inflammation demonstrate that reducing B cells via intravitreal injection of anti-CD20 antibodies attenuates retinal inflammation and microvascular damage.^42^ Collectively, these findings suggest that elevated B-lymphocyte levels may reflect an immune environment predisposing retinal microvasculature to greater susceptibility following ¹³¹I therapy. Although this study cannot establish causality, our results highlight baseline B-lymphocyte levels as a potential modulator of retinal microcirculatory changes in patients with PTC undergoing ¹³¹I treatment.

This study examined optic-disc structures. The results revealed a slight increase in the CDR in patients with PTC following ¹³¹I therapy. Notably, this change occurred without significant alterations in IOP or RNFL thickness, suggesting subtle changes in the optic disc rather than overt glaucomatous damage.^44^ Previous studies have suggested that hypothyroidism elevates IOP by altering the structure of the trabecular meshwork, a key site regulating aqueous humor outflow. In hypothyroid conditions, reduced triiodothyronine levels have been associated with abnormal accumulation of hyaluronic acid within the trabecular meshwork, which may increase outflow resistance and consequently raise IOP.^45^^,^^46^ In this study, patients with PTC exhibited subnormal free thyroxine levels before ¹³¹I therapy and remained in a hypothyroid state. Therefore, the observed increase in CDR may be associated with thyroid hormone imbalance. Epidemiological evidence further supports this interpretation, suggesting an increased glaucoma incidence among individuals with thyroid hormone disorders.^47^ However, given the short follow-up duration and the absence of concomitant RNFL thinning or sustained IOP elevation, the clinical significance of the observed CDR changes remain uncertain. Currently, evidence directly linking ¹³¹I therapy to optic disc structural alterations is limited. Consequently, longitudinal studies with extended follow-up and ophthalmic monitoring are needed to clarify whether these disc changes represent transient adaptive responses.

In summary, this systematic evaluation demonstrates that patients with PTC undergoing ¹³¹I therapy exhibit potential alterations in macular and optic-disc structures, as well as changes in macular microcirculation, characterized by reduced macular thickness and decreased superficial vascular plexus density. These changes may be closely associated with the direct retinal toxicity of radioactive iodine, the systemic inflammatory response induced by ¹³¹I therapy and the pretherapy immune status of the patient, particularly B-lymphocyte levels. Additionally, no clear linear relationship was identified between the therapeutic dose of ¹³¹I and macular thickness. Overall, this study is the first to comprehensively employ OCT and OCTA technologies to characterize the potential ocular effects of ¹³¹I therapy in patients with PTC, thereby providing new insights for clinical monitoring and management.

Conclusions

Following ¹³¹I therapy, patients with PTC exhibit a short-term trend of reduced macular thickness and blood flow. The ¹³¹I dosage and pretreatment B-lymphocyte levels may be associated with post-therapy retinal microcirculation, however, the relationship does not appear to follow a simple linear pattern. Additionally, a slight increase in the CDR is observed after ¹³¹I therapy. These findings highlight the importance of close fundus monitoring in patients with PTC undergoing ¹³¹I therapy.

Study Limitations and Future Directions

Several limitations of this study should be noted. First, the follow-up period focused on short-term changes after ¹³¹I therapy, and longer-term ocular effects could not be evaluated. Second, although appropriate statistical methods were applied to account for inter-eye correlation, the sample size was relatively limited, particularly in subgroup analyses, which may reduce statistical power. Third, OCTA analyses in this study were restricted to the superficial retinal vascular plexus, and potential alterations in the deep retinal capillary plexus were not assessed. Future studies with larger cohorts, extended follow-up durations, and comprehensive OCTA evaluation of both superficial and deep retinal vascular layers are warranted to further clarify the long-term ocular effects of ¹³¹I therapy.

Supplementary Material