A triad of retinal signs in Alport syndrome: The ‘stair-case’ fovea, choroidal thinning and peripheral schisis

Abstract

Background: Alport syndrome is an inherited Type IV collagenopathy characterised by renal failure, hearing loss and ophthalmic manifestations such as lenticonus and dot-and-fleck retinopathy. New signs have been described which can be useful both for diagnosis and for prognosticating the risk of complications. This study examines and describes a triad comprising the unusual ‘stair-case’ foveal sign, together with choroidal thinning and late-stage peripheral schisis in a patient with Alport syndrome. Case presentation: This is a case report of a 49-year-old Caucasian male with a background of X-linked Alport syndrome presenting with gradual and progressive diminution of vision in the left eye with a central blur. He had already undergone three renal allografts, was deaf and suffered from hypertension by the time of his first presentation to ophthalmology. On examination, corrected visual acuity was 6/9.5 in the right eye and 6/30 in the left eye. Optical coherence tomography imaging showed an unusual ‘stair-case’ sign of the fovea in both eyes, together with choroidal thinning. We postulate that an abnormal vitreomacular interface followed by vitreomacular traction and eventually separation, removing layers of the inner retina with the vitreous, led to this unusual appearance. Subsequently, this patient also developed schitic changes more peripherally in the retina which progressed over the following 5 years. Conclusion: The stair-case foveal sign, choroidal thinning and mid-peripheral schisis are three signs that clinicians might expect to encounter on optical coherence tomography imaging of patients with Alport syndrome. These findings can be attributed to unique mutations of collagen IV which lead to a variety of clinical phenotypes affecting basement membrane structures. Identification of these features may not only be useful diagnostically and in forecasting complications such as macular holes, but also predict mode of inheritance and likelihood of early-onset renal failure.

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

“…No treatment was reported in this case report. Ghadiri et al [ 35 ] reported a case in a middle-aged Caucasian male patient who presented with unusual symptoms in his left eye that was described as the same triad of features reported in Stanojcic et al: “stair-case” fovea, choroidal thinning, and peripheral retinoschisis. These signs were associated with unique mutations in COL4A5 .…”

“…AS ocular effects have yet to be proven to be alleviated by surgical approaches, such as vitrectomies, cataract surgeries, and IM peeling [ 29 , 32 , 35 , 37 , 38 , 47 ]. These techniques have been used to help target ocular findings and complications in non-AS patients.…”

“…Although some papers mentioned these surgical techniques in a general patient population, it must be noted that these surgical approaches for AS patients have not been shown to be effective in a large study. For example, one study explained that ophthalmologists should be cautious when considering a vitrectomy in AS patients due to a reduced retinal scaffold [ 35 ]. Vitrectomies are used to repair macular holes, which is a break in the macular region of the retina [ 51 ].…”

Quantitative Optical Coherence Tomography Angiography Biomarkers for Alport Syndrome

“…In AS, the embryonic collagen IV structure (α1α1α2) is not replaced by the mature one (α3α4α5), which results in an increased susceptibility to proteolysis and lesions in tissues rich in type IV collagen (glomerulus, cochlea, cornea, lens, and retina) [3,4]. This disease exhibits variability in its clinical and pathological manifestations and is genetically heterogeneous [5]. About 85% of the AS patients have X-linked inheritance due to mutations in COL4A5, on X chromosome [6].…”

“…Despite being considered a renal disease, 40% of patients present ocular defects as early signs, even preceding proteinuria [9]. The mutation in collagen IV α3α4α5 network caused basement membrane thinning, lamellation, and rarefaction, alongside the intraocular mechanical stresses [5]. Among the broad spectrum of possibilities for ocular manifestations, some could be highlighted, concerning the cornea, lens, and retina.…”