Ocular Manifestations and Potential Treatments of Alport Syndrome: A Systematic Review

Abstract

Objectives. Alport syndrome (AS) is a severe, rare hereditary disorder that can lead to end-stage renal disease, auditory degeneration, and ocular abnormalities. Despite extensive research on AS in relation to auditory and renal disorders, more research is needed on the ocular presentations of AS. This systematic review aims to summarize the common ocular abnormalities in patients with AS and to explore the potential treatment options for these irregularities. Methods. The PubMed, MEDLINE, and EMBASE databases were systematically searched from January 1977 to April 2022. Only papers that were published in the English language and explored the ocular abnormalities in AS patients were selected. We manually searched reference lists of included papers for additional studies. Results. A total of 23 articles involving 195 patients were included in this review. The common ocular manifestations in AS patients are lenticonus, macular holes, fleck retinopathy, and thinning of the macula. Although published literature has described the use of cataract surgeries and vitrectomies as standard surgical techniques to alleviate ocular abnormalities in non-AS patients, it must be noted that surgical techniques have not been evaluated in a large research study as a solution for AS abnormalities. Another prospective treatment for AS is gene therapy through the reversion of causative COL4 variants to wild type or exon-skipping therapy for X-linked AS with COL4A5 truncating mutations. Gene therapy, however, remains unable to treat alterations that occur in the fetal and early development phase of the disease. Conclusions. The review found no definitive conclusions regarding the efficacy and safety of surgical techniques and gene therapy in AS patients. Recognition of ocular abnormalities through an ophthalmic examination with an optical coherence tomography (OCT) and slit-lamp examination is critical to the medical field, as ophthalmologists can aid nephrologists and other physicians in diagnosing AS. Early diagnosis and care can minimize the risk of detrimental ocular outcomes, such as blindness and retinal detachment.

Multimodal Imaging in Unusual Alport Retinopathy

“…Ocular complications in Alport syndrome commonly include dot-and-fleck retinopathy, characterised by white or yellow granulations around the macula [ 3 , 4 ]. Patients may also exhibit anterior lenticonus, in which the lens surface protrudes through a thinned capsule [ 3 , 5 ]. Thinning of the retina is also prevalent and may predispose to symptoms and retinopathy in more extensive disease [ 3 ].…”

Characterization of Ocular Morphology in Col4a3−/− Mice as a Murine Model for Alport Syndrome

“… 1 , 4 , 5 In recent years, ocular manifestations of AS have been increasingly reported. 6 – 8 However, it is difficult to obtain ocular tissue from patients, especially retina and cornea samples; thus, associated research on AS tissue is limited. Studies on ocular changes in patients with AS have focused mainly on clinical manifestations, and few of them have used histologic or molecular research.…”