Progressive Retinal Degeneration and Juvenile Nephronophthisis in a Patient with Autosomal Recessive Ciliopathy: A Case Report

Inherited retinal diseases (IRDs) encompass diverse genetic disorders characterized by progressive retinal degeneration leading to irreversible vision loss [1]. Among these, ciliopathies – a subset of IRDs caused by dysfunction of cilia – are particularly complex due to their multi-systemic involvement, often presenting with concurrent conditions such as nephronophthisis [2, 3]. The intricate pathophysiology of ciliopathies, involving photoreceptor cell death and renal impairment, poses significant challenges in patient management and treatment development.

Recent advancements in genetic testing have facilitated the identification of specific genetic variants responsible for IRDs, enabling personalized therapeutic approaches [4]. Despite these advancements, treatment options remain limited, predominantly focusing on supportive care and symptom management [5]. Nutritional interventions have emerged as a promising supplementary strategy to potentially slow disease progression and improve the quality of life in patients with IRDs. Nutrients such as antioxidants and specific vitamins have demonstrated roles in supporting retinal health and mitigating oxidative stress [6‒9]. Additionally, tailored dietary modifications are essential for patients with concurrent renal impairment to manage both ocular and systemic health effectively.

This case report details a 30-year-old male patient with progressive retinal degeneration and juvenile nephronophthisis associated with variants in CEP83, PCARE, and VPS13B genes. The report emphasizes the role of nutritional strategies in managing complex multi-systemic conditions and discusses the broader policy implications for integrating nutritional education and support in the care of patients with ciliopathies. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000543419).

A 30-year-old male presented with a long history of gradual vision loss and photophobia in both eyes. His corrected distance visual acuity was 20/70 in the right eye (OD) and 20/100 in the left eye (OS). Intraocular pressure and anterior segment examinations were within normal limits. Fundus examination revealed cup-to-disc ratios of 0.1 in both eyes, vascular changes indicative of hypertensive retinopathy, and stable outer retinal atrophy with retinal pigment epithelium alterations in the parafoveal region (Fig. 1). Optical coherence tomography confirmed the thinning of the outer retina and disruption of the retinal pigment epithelium in both eyes (Fig. 2).

The patient’s medical history included medically managed hypertension and end-stage renal disease secondary to juvenile nephronophthisis. He is currently on the waiting list for a kidney transplant. The patient reported poor vision starting at age 8, with gradual deterioration over the years. He denied any family history of ocular or genetic diseases.

Comprehensive genetic testing identified pathogenic variants in three genes classified based on ACMG guidelines considering in silico predictions, population frequencies, and published literature. Two likely pathogenic variants in CEP83 (compound heterozygous), associated with autosomal recessive nephronophthisis [10]; and two likely pathogenic variants in PCARE (compound heterozygous), linked to autosomal recessive retinal degeneration [11], were identified. Additionally, a heterozygous variant of uncertain significance in VPS13B, implicated in autosomal recessive Cohen syndrome, characterized by retinal dystrophy and developmental delay [12], was noted. No other relevant variants were found. These genetic findings confirmed the diagnosis of the ciliopathy autosomal recessive retinitis pigmentosa.

In this patient with variant CEP83, PCARE, and VPS13B genes, a tailored nutritional intervention was implemented to support both ocular and renal functions. Given the patient’s end-stage renal disease, dietary adjustments were essential to manage nutrient absorption and metabolism, which directly affect ocular health. Although some preliminary reports suggest anti-inflammatory and neuroprotective roles of omega-3 fatty acids and antioxidants, the evidence for slowing retinal degeneration remains limited. Therefore, these supplements were offered to the patient with the understanding that they were adjunctive and not a definitive therapy. Additionally, renal-specific dietary modifications such as protein restriction, phosphorous control, and electrolyte balance maintenance were offered.

Moreover, the management of systemic hypertension was optimized through dietary sodium and potassium regulation, thereby mitigating further vascular damage to the retina associated with hypertensive retinopathy. The integration of these nutritional strategies with standard medical treatments contributed to the stabilization of retinal degeneration and improved overall management of the patient’s multi-systemic condition.

IRDs represent a significant cause of blindness globally, with ciliopathies being particularly challenging due to their multi-systemic manifestations [1, 2]. This case underscores the critical need for a holistic management approach that transcends traditional ocular-focused treatments, incorporating nutritional strategies to address the complex interplay between retinal and renal health in ciliopathies.

The identification of pathogenic variants in CEP83, PCARE, and VPS13B genes in this patient not only elucidates the genetic underpinnings of his autosomal recessive retinitis pigmentosa and juvenile nephronophthisis but also provides actionable targets for personalized therapeutic interventions [10‒12]. Nutritional interventions, as implemented in this case, offer a promising adjunct to standard care by potentially slowing the progression of retinal degeneration and supporting renal function.

Antioxidants have been extensively studied for their roles in retinal health, demonstrating protective effects against oxidative stress and photoreceptor cell death [5, 7]. Similarly, tailored dietary modifications for renal impairment, such as protein restriction and electrolyte management, are critical in preventing further systemic complications [8, 13]. The concurrent management of hypertension through dietary sodium and potassium regulation further exemplifies the multifaceted benefits of integrated nutritional strategies.

This case also highlights broader policy implications, advocating for the inclusion of nutritional education and support within clinical guidelines for managing ciliopathies. Establishing standardized nutritional protocols can enhance patient outcomes and reduce the burden of multi-systemic complications. Moreover, advocating for insurance coverage of nutritional counseling and necessary supplements is imperative to ensure equitable access to comprehensive care.

Despite the promising outcomes observed in this case, limitations exist, including the inherent constraints of a single-case report and the need for longitudinal studies to substantiate the efficacy of nutritional interventions in ciliopathies. Future research should aim to delineate the precise mechanisms by which specific nutrients influence retinal and renal pathology, and to optimize dietary regimens tailored to individual genetic profiles.

In conclusion, the integration of personalized nutritional interventions alongside conventional medical therapies presents a viable strategy for improving outcomes in patients with IRDs, particularly those with ciliopathies. This holistic approach not only addresses the ocular manifestations but also mitigates systemic complications, thereby enhancing overall patient quality of life. Collaborative efforts among healthcare providers, researchers, and policymakers are essential to advance comprehensive care models for individuals with inherited ciliopathies.

This case report was conducted in accordance with the Declaration of Helsinki. The collection and evaluation of all protected patient health information were performed in a HIPAA (Health Insurance Portability and Accountability Act)-compliant manner. Ethical approval is not required for this study in accordance with local or national guidelines. The patient provided informed consent for diagnosis, genetic testing, treatment, and follow-up, as per the standard of care in the USA. Written informed consent for the publication of details was obtained from the patient.

D.A. has received financial support in the form of research grants, funding, and materials from Alumis, Acylerin, Alcon, Alimera Sciences, Allergan/AbbVie, Bausch + Lomb, Bayer, Boehringer Ingelheim, Dutch Ophthalmics, Eyepoint Pharmaceuticals, Genentech, Gyro-scope Therapeutics, Novartis, Ocugen, Opthea, Regeneron, Regenxbio, Roche, and Samsara Vision. D.A. also holds equity and leadership positions in organizations including Citrus Therapeutics, Erie Retina Research, Erie Dry Eye Research, ELEMENT: Reading Center @ Erie, KPeye, REACT: Research in Advanced Technologies, and ACT: Applied Clinical Technologies, and serves as a consultant for Alimera Sciences, Allergan/AbbVie, Alumis, Boehringer Ingelheim, Genentech, and Regeneron. E.C. has received research support and served as a co-investigator for Kyowa Kirin, Janssen Bio-logics, Kodiak, OnPoint Vision, Genentech, Oculis, Bayer, Clearside Biomedical, Valo Health, Inc., and Opthea. E.C. is a co-founder of Citrus Therapeutics and a shareholder in Apellis. J.P. declares no conflicts of interest.

This study was not supported by any sponsor or funder.

Conceptualization and validation: D.A. and E.C.; methodology, investigation, supervision, project administration, and resources: writing – original draft preparation, J.P.; writing – review and editing: J.P., E.C., and D.A.; visualization: J.P., D.A., D.A.

The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from the corresponding author D.A.