Case Report
Isolated foveal hypoplasia in a diabetes patient: a case report
https://doi.org/10.21203/rs.3.rs-4835636/v1
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Isolated foveal hypoplasia is a rare cause of visual loss. Here, we report the unusual clinical presentation of a 61-year-old Chinese men who presented with hard exudates of low density in the temporal retina, absent foveal reflex, and foveal hypoplasia. The best corrected visual acuity (BCVA) was 0.9 and 0.7 (right and left eye respectively). This case highlights the importance of multicolour imaging to help distinguish or study isolated foveal hypoplasia.
Isolated foveal hypoplasia
OCTA
ERG
fundus photo
A 61-year-old Chinese men who was previously diagnosed with diabetes presented to Jiangning Traditional Chinese Medicine Hospital for evaluation of the ocular fundus. He was born at full term and had no significant family history of genetic eye disease. A slit-lamp examination revealed mild opacity of the lens in both eyes. Rest of the anterior segment was normal. Best corrected visual acuity (BCVA) was 0.9 and 0.7 (right and left eye respectively). No night vision difficulty was reported. His intraocular pressure was normal. Fundus examination revealed a bilateral flat retina with a healthy disc, normal retinal vessels, hard exudates of low density in the temporal retina, and an absent foveal reflex in the left eye (Fig. 1). OCT revealed foveal hypoplasia in the left eye with maintenance of all the inner retinal layers and outer plexiform layer in the typical foveal pit location (Fig. 2). OCT imaging revealed grade 1 foveal hypoplasia. Grade 1 foveal hypoplasia is characterized by shallower foveal pits, outer nuclear layer (ONL) widening, and the absence of lengthening of the outer segments of photoreceptors (OS)[1]. OCT-angiography (OCTA) imaging revealed the absence of a foveal avascular zone (FAZ) in the left eye. Full-field electroretinography (ERG) revealed that the patient had extinguished rod and cone responses in the left eye (Fig. 3). Ophthalmic examinations of the patient's only son and elder brother revealed no abnormalities. Taken together, a diagnosis of isolated foveal hypoplasia was given.
The normal development of the foveal depression in the human macula initiates at the 25th week of gestation and is completed between 15 and 45 months postnatally. The bidirectional movement of neurons within the inner and outer layers of the retina molds the formation of the foveal depression; inner retinal cells undergo centrifugal displacement to form the foveal pit, whereas cone cells shift centripetally, resulting in increased density of cone cells within the fovea[2]. During the late stages of pregnancy and after birth, ganglion cells and the cells of the inner nuclear layer continue to displace centrifugally away from the fovea. By the age of 4, the density of cone cells at the fovea can reach 108,000 cells/mm2[3]. The fovea is comprised of cone cells and Müller cells. Müller cells might produce molecules such as pigment epithelium-derived growth factor and brain natriuretic peptide, which inhibit astrocytes and angiogenic cells from migrating into the fovea, thus creating an astrocyte-free zone[4]. Moreover, astrocytes can induce the migration of retinal angiogenic cells, therefore the absence of astrocytes is important for the development of the foveal avascular zone (FAZ)[5]. The FAZ is an essential prerequisite for the development of the fovea, and the size of the FAZ dictates the structure of the fovea[2]. The appearance of the macular pigment at approximately 17 weeks of gestation contributes to the formation of the FAZ, and its spatial distribution is correlated with the size of the FAZ and the thickness of the fovea[6].
Foveal hypoplasia (FH) is mainly characterized by the reduction or absence of the foveal depression and the foveal avascular zone (FAZ), representing a retinal disorder that may occur in isolation or in conjunction with other ocular or systemic diseases[7]. The advancement of OCT imaging has provided new characteristics for foveal hypoplasia accompanying known retinal diseases. Thomas and colleagues[1] proposed a structural grading system for foveal hypoplasia based on OCT cross-sectional images: Grade 1 with shallow foveal pit, thickening of the outer nuclear layer (ONL) and elongation of the photoreceptor outer segments (OS); Grade 2 with absence of the foveal pit; Grade 3 without elongation of the OS; and Grade 4 without ONL thickening. Grades 1 and 2 represent the absence of pit formation with complete cone specialization, while Grades 3 and 4 indicate failure of cone specialization.
FH can be observed in conditions such as albinism, aniridia, retinopathy of prematurity, and isolated foveal hypoplasia. Oculocutaneous albinism is a group of autosomal recessive genetic disorders characterized by impaired melanin synthesis, leading to reduced pigmentation in the eyes, skin, and hair[8]. Ocular albinism is an X-linked recessive genetic disorder that affects only the eyes. The ocular symptoms of both oculocutaneous and ocular albinism include poor vision, nystagmus, strabismus, depigmentation of the uvea, and foveal hypoplasia. Patients with albinism lack the rod-free area crucial for the specialization of cones and also lack macular pigment deposition, which is thought to be related to poor vision[9]. Aniridia is caused by mutations in the PAX6 gene. The degree of foveal hypoplasia is related to the severity of iris defects[10]. Retinopathy of prematurity arises from retinal hypoxia due to halting the development of retinal blood vessels. The capillary network around the fovea forms in the late stages of pregnancy, and foveal development may be affected by prematurity [5]. Studies have found that children with retinopathy of prematurity have a smaller or absent FAZ, accompanied by increased retinal thickness at the macular center and increased density of the superficial retinal vascular network[11]. Isolated foveal hypoplasia is related to hypomorphic mutations of the PAX6 gene and mutations in the SLC38A8 gene, with autosomal dominant and autosomal recessive inheritance patterns, respectively[12, 13].Prior to the patient's consultation, there were no symptoms of eye discomfort or vision loss. However, OCT showed continuous changes from the retinal nerve fiber layer to the outer nuclear layer in the macular region of the left eye, with thickening of the outer nuclear layer and a shallow foveal pit, indicating Grade 1 foveal hypoplasia. Reports have demonstrated that FH does not have a clear structure-function correlation. Mota reported that the inhibited development of the fovea does not affect the prognosis of best-corrected visual acuity[14]. Marmor described the best-corrected visual acuity of four patients with foveal hypoplasia ranging from 20/20 to 20/50[15]. Even without a foveal pit, cone specialization in the fovea can be anatomically and functionally preserved[16]. This explains why the patient in this case, despite lacking a normal foveal depression, may still possess relatively good vision. The patient's son and elder brother did not exhibit foveal hypoplasia, and in the absence of genetic testing results, the etiology remains unclear.
Corresponding author: Xi Chen
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Authors and Affiliations
Department of ophthalmology，Jiangning TCM Hospital，Nanjing 211100，China
Yifan Wang , Zhaoyang Dong and Zhuojun Yin
The Affiliated Hospital of Nanjing University of Chinese Medicine，Jiangsu Province Hospital of Chinese Medicine，Nanjing 210029，China
Xi Chen
Contributions
YW and ZD drafted and edited the main manuscript text. XC reviewed the main manuscript text. The case was discovered by ZY. All the authors contributed to the article and approved the submitted version.
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Consent for publication
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
Competing interests
The authors declare no competing interests.
No competing interests reported.
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