International Journal Publication | Collaborative Team of Dr. Tong Wu, Dr. Zhihui Li, and Prof. Yong Tao Reports First Case of Purtscher-Like Retinopathy After CAR-T Bridging to Allo-HSCT

Summary: A collaborative team led by Dr. Tong Wu and Dr. Zhihui Li of Beijing GoBroad Boren Hospital and Prof. Yong Tao of Beijing Chaoyang Hospital, Capital Medical University, published a case report in Frontiers in Immunology describing, for the first time, a rare case of Purtscher-like retinopathy (PLR) in a child with relapsed B-ALL after CAR-T therapy bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT). The study details the retinal imaging features of PLR, the response to anti-VEGF treatment, and its potential mechanistic relationship with transplant-associated thrombotic microangiopathy (TA-TMA). The findings highlight the importance of recognizing atypical complications that may reflect broader systemic changes in patients receiving complex immunotherapy and transplantation.

As CAR-T cell therapy becomes more widely used for relapsed or refractory hematologic malignancies, more patients are achieving deep remissions and moving on to hematopoietic stem cell transplantation. At the same time, the use of multiple sequential immunotherapies can make post-transplant complications more complex. In this setting, recognizing atypical complications early and avoiding delays in intervention has become an increasingly important issue in clinical practice.

Recently, a collaborative team with Dr. Tong Wu of Beijing GoBroad Boren Hospital and Prof. Yong Tao of Beijing Chaoyang Hospital, Capital Medical University, as co-corresponding authors, and Dr. Zhihui Li of Beijing GoBroad Boren Hospital as first author, published a case report in Frontiers in Immunology. The team provided the first systematic report of a rare case of Purtscher-like retinopathy (PLR) occurring after CAR-T therapy bridging to allogeneic hematopoietic stem cell transplantation and explored its potential mechanistic association with transplant-associated thrombotic microangiopathy (TA-TMA).

Dr. Zhihui Li noted that, in clinical practice, some complications do not initially present with typical hematologic abnormalities. Instead, they may first appear as localized, nonspecific symptoms, making early recognition more difficult. Against this background, the team systematically reviewed and analyzed the rare ocular findings that developed after CAR-T therapy and transplantation in this case, with the aim of drawing attention to the possible systemic significance behind atypical manifestations in patients receiving complex immunotherapy.

Case Overview

From Multiple Lines of Immunotherapy to Transplantation: Reviewing a Complex Treatment Journey

The study describes a child with relapsed B-cell acute lymphoblastic leukemia (B-ALL). After the initial diagnosis, the patient received standard treatment and achieved remission, but experienced the first hematologic relapse approximately 2.5 years later. To regain disease control, the patient received CD19 CAR-T cell therapy and achieved remission, followed sequentially by CD22 CAR-T cell therapy to further consolidate disease control and reduce the risk of antigen escape.

In 2024, the disease progressed again and relapsed with extramedullary involvement. At this stage, the treatment strategy shifted toward antibody-based immunotherapy in an effort to achieve another remission. The patient received an anti-CD22 antibody-drug conjugate, inotuzumab ozogamicin, together with immunomodulatory therapy such as belimumab. Once an appropriate transplant window was achieved, the patient proceeded to allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Recognizing and Managing Sudden Vision Changes: Imaging Features of PLR and Response to Treatment

Approximately 160 days after transplantation, the patient developed sudden, painless loss of vision accompanied by visual distortion, with no history of trauma. A comprehensive ophthalmologic evaluation, including fundus photography (Figure 1A & B), optical coherence tomography (OCT; Figure 2A & B), and fluorescein fundus angiography, led to a diagnosis of Purtscher-like retinopathy (PLR).

The patient first received a 0.5 mg intravitreal injection of ranibizumab in the left eye, administered once monthly. Six days after the first injection, vision in the left eye improved markedly, with substantial reductions in optic disc edema and retinal hemorrhage (Figures 1D and 2D).

To further investigate the underlying mechanism, the research team performed a cytometric bead array (CBA) analysis of aqueous humor. Levels of basic fibroblast growth factor (bFGF) and vascular cell adhesion molecule-1 (VCAM-1) were significantly elevated, suggesting disruption of the blood-retinal barrier.

During this period, vision in the right eye deteriorated rapidly, accompanied by increased retinal hemorrhage and cotton-wool spots, as well as worsening optic disc edema (Figures 1C and 2F). The team subsequently initiated a 0.5 mg intravitreal ranibizumab injection in the right eye.

Eight days after the first injection in the right eye, vision in the left eye continued to improve. Although vision in the right eye did not improve further, fundus examinations of both eyes showed marked reductions in retinal hemorrhage, cotton-wool spots, and optic disc edema (Figures 1E, F; Figures 2E, F), suggesting that anti-VEGF therapy had a positive effect on controlling retinal microvascular lesions.

Figure 1. Fundus photographs of both eyes

(A, B) Multiple retinal hemorrhages, cotton-wool spots, and yellow-white Purtscher flecken are visible in the posterior poles of both eyes, with more extensive involvement in the left eye.

(C) Compared with the earlier examination, retinal hemorrhage, cotton-wool spots, and Purtscher flecken are markedly increased in the right eye.

(D) Six days after intravitreal ranibizumab injection in the left eye, retinal hemorrhage is partially absorbed, while the cotton-wool spots and Purtscher flecken show little change.

(E) Eight days after intravitreal ranibizumab injection in the right eye, retinal hemorrhage, cotton-wool spots, and Purtscher flecken are markedly reduced compared with the previous examination.

(F) Fifteen days after intravitreal ranibizumab injection in the left eye, retinal hemorrhage shows further absorption, with additional reductions in cotton-wool spots and Purtscher flecken.

Figure 2. OCT images of both eyes

(A) Right eye (February 19): Edema and thickening of the inner retina with cystoid macular edema measuring approximately 249 μm.

(B) Left eye (February 19): Marked edema and thickening of the inner retina, with cystoid macular edema measuring approximately 885 μm and multiple focal hyperreflective lesions.

(C) Right eye (March 3): Further worsening of inner retinal edema and thickening, with cystoid macular edema measuring approximately 822 μm, markedly increased from the previous examination.

(D) Left eye (March 3): Reduced inner retinal edema and thickening, with cystoid macular edema measuring approximately 358 μm, markedly decreased from the previous examination.

(E) Right eye (March 12): Marked improvement in inner retinal edema and thickening, with cystoid macular edema measuring approximately 253 μm, substantially reduced from prior examinations.

(F) Left eye (March 12): Cystoid macular edema measures approximately 260 μm, with little change compared with the previous image.

From Retinal Findings to Systemic Assessment: Recognition and Management of TA-TMA

While evaluating and treating the ocular lesions, the research team also carried out a systemic assessment. On post-transplant day 179, lymphocyte subset analysis showed a CD4/CD8 ratio of 0.22, B cells at 5.05%, and NK cells at 21.68%, indicating limited immune reconstitution.

By post-transplant day 194, the patient had developed severe thrombocytopenia, with a nadir platelet count of 40 × 10^9/L, marked proteinuria (24-hour urinary protein, 2,400 mg), renal impairment (serum creatinine, 133.9 μmol/L), and complement activation (C5b-9, 298 ng/mL), together with serous effusions in multiple body cavities.

Following a systematic evaluation, graft-versus-host disease (GVHD), calcineurin inhibitor toxicity, and other potential causes were excluded. Together with an increased proportion of schistocytes in peripheral blood (0.8%), the findings led to a diagnosis of transplant-associated thrombotic microangiopathy (TA-TMA).

For TA-TMA, the patient received defibrotide and eculizumab, together with supportive treatment including diuretics, antihypertensive therapy, and management of capillary leak. The patient's overall condition subsequently stabilized.

Summary and Outlook

Dr. Zhihui Li noted that this study provides the first systematic report of Purtscher-like retinopathy occurring in a child with relapsed B-ALL after CAR-T therapy bridging to allogeneic hematopoietic stem cell transplantation. Importantly, in this case, the retinal manifestations appeared before some of the systemic abnormalities, offering a new perspective on how post-transplant microvascular complications may evolve. As immunotherapy and transplantation are increasingly integrated, clinicians need to pay closer attention to atypical symptoms such as sudden vision changes. Combining imaging evaluation with systemic assessment may help identify underlying microvascular injury or complement-related abnormalities at an earlier stage and allow timely management. Multidisciplinary collaboration and careful, individualized assessment may further improve the recognition and management of post-transplant complications, enhancing overall treatment safety and outcomes.

Prof. Yong Tao commented: “As patients with hematologic diseases increasingly survive intensive treatment, protecting quality of life becomes equally important. Vision accounts for more than 90% of the information people take in from the world, and irreversible vision loss can place a heavy burden on the patient's daily life, work, and family. This report describes Purtscher-like retinopathy in a child with relapsed B-ALL after CAR-T therapy bridging to allogeneic hematopoietic stem cell transplantation. Although active treatment reduced retinal edema and gradually improved ischemic changes, the patient was still left with severe, irreversible visual impairment. We hope this case encourages clinicians to move screening earlier in the care pathway by considering routine fundus examinations for high-risk patients, using AI-assisted screening where appropriate, identifying retinal abnormalities as early as possible, and intervening promptly.”