Bilateral active chorioretinal lesions and fundus hemorrhage in a 23-month-old male with CYBB mutation: a case report
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Key findings
• Chorioretinal lesions in cases of chronic granulomatous disease (CGD) are mostly inactive and tend not to affect vision. We present a rare case of bilateral active chorioretinal lesions and fundus hemorrhage in a 23-month-old male with CYBB mutation.
What is known and what is new?
• Chorioretinal lesions in CGD are mostly inactive and tend not to affect vision, and they appear as “punched-out”, atrophic chorioretinal scars with pigment clumping around the vessels.
• Active chorioretinal lesions and fundus hemorrhage in CGD are rare, and vision loss may occur in severe cases.
What is the implication, and what should change now?
• When patients with CGD have decreased visual acuity, timely fundoscopic evaluation by an ophthalmologist is necessary.
Introduction
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disease caused by mutations in the CYBB, CYBA, NCF1, NCF2, and NCF4 genes, which impair NADPH oxidase activity in phagocytes. It is inherited through X-linked or autosomal recessive (AR) modes, with the X-linked CYBB mutation being the most common type (1). The clinical manifestations of CGD are recurrent bacterial and fungal infections, granuloma formation, and noninfectious inflammatory responses, which affect multiple organs, including the lung, skin, liver, and gastrointestinal tract; however, ocular involvement is rare (2). Ocular complications of CGD include uveitis, keratitis, conjunctivitis, optic atrophy, glaucoma, and, mostly commonly, chorioretinal granulomatous lesion (3,4). The frequency of ocular lesions may be due to a lack of awareness. Studies have suggested that chorioretinal lesions are mostly inactive and tend not to affect vision; they appear as “punched-out”, atrophic chorioretinal scars with pigment clumping around the vessels (3). Active lesions with fundus hemorrhage in CGD are rare, and vision loss may only occur in severe cases. We present this article in accordance with the CARE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0080/rc).
Case presentation
A 17-month-old male child was initially admitted to hospital due to fever lasting 1 week. There was no family history of immunodeficiency. Abdominal ultrasound (US) scan and computerized tomography (CT) both showed localized intestinal wall thickening (about 8 mm) in the right upper abdominal cavity, extensive lymphadenopathy, multiple abscesses of the liver and spleen, and ascites. Ascitic culture indicated the presence of Burkholderia cepacia, and subsequent genetic testing confirmed CGD (CYBB gene mutation, c.603C > A). Dihydrorhodamine functional assay showed a marked decrease in NADPH activity (139 F/µg; reference value 1,332–9,312 F/µg) and relative activity 3% of normal (reference value 31–216%).
At 23 months of age, the patient was rehospitalized due to a fever lasting 1 month and decreased visual acuity in both eyes. He had poor eye contact with his parents, needed help walking, and was unable to actively avoid obstacles. Physical examination revealed significant hepatomegaly and splenomegaly but no cardiopulmonary abnormalities. The findings from complete blood count were as follows: hemoglobin, 53 g/L; leukocyte, 16.12×109/L; neutrophil, 48%; lymphocyte, 47%; monocyte, 5%; and thrombocyte, 33×109/L. The findings from other tests were as follows: C-reactive protein, 12.72 mg/dL (normal value <0.8 mg/dL); procalcitonin, 1.14 ng/mL (normal value <0.05 ng/mL); alanine aminotransferase, 20 U/L (normal value 7–30 U/L); aspartate aminotransferase, 61 U/L (normal value 14–44 U/L); gamma-glutamyl transferase, 139 U/L (normal value 5–19 U/L); renal function, normal; serum immunoglobulins and lymphocyte subsets, normal. Interferon-gamma release assay and other pathogens tests (including those for cytomegalovirus, herpes simplex virus, and syphilis) were all negative. Abdominal US and CT scans indicated significant hepatomegaly and splenomegaly. Chest CT revealed scattered infection in the lungs. Orbital magnetic resonance imaging excluded mass lesions (Figure 1). The findings from ophthalmologic examination were as follows: clear cornea in both eyes, 2+ aqueous flare in the right eye, 1+ aqueous flare in the left eye, bilateral vitreous opacities, reduced light pursuit in the left eye, absent light pursuit in the right eye, bilateral chorioretinal lesions, and extensive fundus hemorrhage in the right eye (Figure 2). Subsequently, our patient received treatment with meropenem, linezolid, voriconazole, rifampicin, intravenous immunoglobulin (2 g/kg), dexamethasone (0.3 mg/kg.d), and transfusion of red blood cells to correct anemia. Extensive fundus hemorrhage made surgery infeasible, and no other treatment was provided by the ophthalmologist. Ten days later, the patient was discharged.
However, he missed the scheduled follow-up. He did not take oral drugs regularly to prevent infections, and he was rehospitalized occasionally due to fever. The patients is currently 6 years old; he lacks light perception in the right eye and has poor light perception in the left eye.
All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Ethics Committee of Tianjin Children’s Hospital (Tianjin University Children’s Hospital) (No. W-2025-050). Written informed consent was obtained from the patient’s parents for publication of this case report and accompanying images.
Discussion
Chorioretinal lesions in patients with CGD were first described in 1965, and the reported incidence in subsequent studies ranges from 12.5% to 35.3% (5-7). These lesions occur in patients with both with X-linked and AR-related disease, and there is no genotype-phenotype correlation. Cases of chorioretinal lesions in asymptomatic CGD carriers have been reported, which may be associated with skewed X-inactivation (8). Ocular lesions can occur in any stage of disease (9), and they can be the initial presentation of CGD (10).
The chorioretinal lesions in CGD are typically described as inactive, punched-out, atrophic chorioretinal scars and may remain inactive for long periods without impairing vision. The majority of patients are asymptomatic and are incidentally diagnosed during regular ophthalmic examinations; a portion of patients may experience vision loss due to fundus hemorrhage, retinal detachment, or retinal ischemia, and some severe cases require eye enucleation due to giant granuloma. Ophthalmoscopic examination of our patient showed extensive fundus hemorrhage in the right eye. There are few reports on patients with CGD and fundus hemorrhage (Table 1). The majority of such patients are male, and among them, three experienced improved vision after treatment, two patients underwent eye enucleation, and one male child had a similar profile to that of our patient: he had a history of recurrent infections and chest infection with Burkholderia cepacia, and he ultimately lost light perception ability.
Table 1
| Case | Sex (Ref.) | Age at CGD diagnosis | Age at ocular lesion emergence | Ocular symptoms | Ophthalmoscopic examination | Other clinical symptoms | Treatment | Prognosis |
|---|---|---|---|---|---|---|---|---|
| 1 | M (6) | 15 m | 7 y | Decreased visual acuity in the right eye | Multiple punched-out lesions, multiple small inflammatory lesions, neovascular membrane, and vitreous hemorrhage | Lymphadenitis and perianal abscesses | Vitrectomy and laser photocoagulation | Visual acuity 20/25 (right) |
| 2 | F (6) | 3 y | 11 y | Decreased visual acuity in both eyes | Multiple retinal inflammatory lesions and preretinal hemorrhage | Recurrent pneumonia | Steroid pulse therapy and laser photocoagulation | Visual acuity 20/25 in the right eye and 5/20 in the left eye |
| 3 | M (11) | NA | 10 y | Sudden loss of vision in the left eye | Vitreous hemorrhage and cystoid macula oedema | NA | Injection of 30 mg of triamcinolone | Decreased vision to 6/12 (left) |
| 4 | M (7) | 13 m | 3 y | New-onset strabismus in the right eye | Bilateral chorioretinal lesions, retinal detachment, vision loss, and uveitis | Skin, spleen abscess, chest infection (Burkholderia cepacia), and pulmonary aspergillosis | No treatment due to retinal detachment | Absence of light perception in the right eye and reduced light perception in the left eye |
| 5 | M (12) | 1 m | 3 y | Sudden onset of redness, pain, and photophobia in the left eye | Vitreous hemorrhage and retinal detachment | Recurrent lymphadenitis and pneumonia | Vitrectomy, lensectomy, and enucleation of the left eye | Enucleation of the left eye |
| 6 | M (12) | NA | 12 m | Intermittent esotropia in the left eye | Chorioretinal lesions, preretinal hemorrhage, and vitreous hemorrhage | NA | Enucleation of the left eye | Enucleation of the left eye |
CGD, chronic granulomatous disease; F, female; m, months; M, male; NA, not available; y, years.
The pathogenesis of chorioretinal lesions has not been fully clarified. CGD is caused by reduced activity of the NADPH oxidase complex and thus a failure to produce reactive oxygen species in phagocytes. The retinal pigment epithelium (RPE) has a macrophage-like function and may be involved in the emergence of chorioretinal lesions. A few ocular pathological studies have identified choroidal granulomatous lesions in ocular tissues to be sterile abscesses and have suggested that granulomatous inflammation likely occurs secondary to undigested intracellular bacterial debris resulting from recurrent infection (12-14). Our patient experienced visual impairment 6 months after the initial diagnosis of CGD. Recurrent infections (especially with Burkholderia cepacia) may be a trigger for chorioretinal lesions. Abnormality in RPE function causes the formation of local granulomatous lesions, and inflammatory responses may continue even after eradication of the initiating infectious agent.
Stem cell transplantation is currently the only curative treatment for CGD, with the alternative therapies being long-term antibiotic and antifungal prophylaxis—which can reduce the risk of severe infections—or recombinant human interferon gamma (15). There is no standard treatment for chorioretinal lesions. Vitreoretinal surgery may be indicated after ophthalmic evaluation, but in our patient, surgery was not recommended by the ophthalmologist due to extensive fundus hemorrhage. Ultimately, severe visual impairment occurred.
Conclusions
Chorioretinal lesions in patients with CGD are usually inactive and remain asymptomatic for an extended period of time. Although reports of active lesions complicated by fundus hemorrhage are rare, this condition can cause vision loss. Recurrent infections may be a trigger for the emergence chorioretinal lesions. When patients with CGD experience decreased visual acuity, timely fundoscopic evaluation by an ophthalmologist is necessary.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0080/rc
Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0080/prf
Funding: This study was supported by
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0080/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Ethics Committee of Tianjin Children’s Hospital (Tianjin University Children’s Hospital) (No. W-2025-050). Written informed consent was obtained from the patient’s parents for publication of this case report and accompanying images.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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(English Language Editor: J. Gray)
