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A Young Boy With Changes in the Retinal Pigment Epithelium

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 9-year-old boy was referred to a pediatric retina specialist for evaluation of changes in the peripheral retinal pigment epithelium. Ocular history included high hyperopia and amblyopia, and abnormal foveal contour was discovered when he was aged 3 years. Family history was noncontributory. Best-corrected visual acuity was 20/50 in the right eye and 20/30 in the left. Pupils were round and reactive to light, and intraocular pressure and anterior segment examination were within normal limits. Dilated fundus examination revealed blunted foveal reflexes and abnormal vasculature in the inferonasal quadrant of the right eye. Fluorescein angiography displayed symmetric bilateral circular areas of hypofluorescence around the macula and irregular fovea with no leakage (Figure 1A). Color fundus photography showed symmetric bilateral mottling of the retinal pigment epithelium in the periphery (Figure 1B). Spectral-domain optical coherence tomography on initial examination showed an abnormal foveal contour with loss of the foveal pit and intraretinal cystoid cavities within the inner nuclear layer.

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Congenital nanophthalmos

B. Genetic testing to assess for ocular diseases

Nanophthalmos, which affects ocular development, is the most prevalent genetic congenital ocular disorder.1,2 It is characterized phenotypically by small eyes and normally presents without associated structural defects1 and with high hyperopia secondary to severely decreased axial length.3 Mean best-corrected visual acuity ranges from 20/25 to 20/50.4 Posterior involvement can lead to an irregular fovea (Figure 1), papillomacular folds, abnormal foveal contour, and uveal effusions. Patients with nanophthalmos have an increased risk of developing acute angle-closure glaucoma, retinal detachment, and intraretinal cysts (Figure 2).2 The schisislike cystoid thickening of the retina has been proposed to arise from crowding of the retina and uveal tissues and poor outflow through the characteristically thickened sclera. Although literature on the angiographic characterization of this phenomenon is limited, fundus autofluorescence is not expected to show leakage surrounding these spaces.5,6

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Article Information

Corresponding Author: Audina M. Berrocal, MD, Bascom Palmer Eye Institute, 900 NW 17th St, 2nd Floor, Miami, FL 33136 (aberrocal@med.miami.edu).

Published Online: July 21, 2022. doi:10.1001/jamaophthalmol.2022.1653

Conflict of Interest Disclosures: Dr Berrocal has financial interests in Aerie Pharmaceuticals, ProQR Therapeutics, Oculus Surgical, Alcon, Allergan, Bayer, Dutch Ophthalmic Research Center, Phoenix Clinical, Vizunex Medical Systems, Zeiss, and Novartis. No other disclosures were reported.

Funding/Support: This work was supported by National Institutes of Health Center Core grant P30EY014801, Research to Prevent Blindness unrestricted grant GR004596, and US Department of Defense grant W81XWH-13-1-0048.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank the patient’s family for granting permission to publish this information.

Sundin  OH , Dharmaraj  S , Bhutto  IA ,  et al.  Developmental basis of nanophthalmos: MFRP is required for both prenatal ocular growth and postnatal emmetropization.   Ophthalmic Genet. 2008;29(1):1-9."https://pubmed.ncbi.nlm.nih.gov/18363166" doi:10.1080/13816810701651241PubMedGoogle Scholar
Almoallem  B , Arno  G , De Zaeytijd  J ,  et al.  The majority of autosomal recessive nanophthalmos and posterior microphthalmia can be attributed to biallelic sequence and structural variants in MFRP and PRSS56.   Sci Rep. 2020;10(1):1289. doi:10.1038/s41598-019-57338-2Google ScholarCrossref
Sundin  OH , Leppert  GS , Silva  ED ,  et al.  Extreme hyperopia is the result of null mutations in MFRP, which encodes a Frizzled-related protein.   Proc Natl Acad Sci U S A. 2005;102(27):9553-9558. doi:10.1073/pnas.0501451102PubMedGoogle ScholarCrossref
Okumichi  H , Itakura  K , Yuasa  Y , Fukuto  A , Kiuchi  Y .  Foveal structure in nanophthalmos and visual acuity.   Int Ophthalmol. 2021;41(3):805-813. doi:10.1007/s10792-020-01633-9PubMedGoogle ScholarCrossref
Dhrami-Gavazi  E , Schiff  WM , Barile  GR .  Nanophthalmos and acquired retinoschisis.   Am J Ophthalmol. 2009;147(1):108-110.e1. doi:10.1016/j.ajo.2008.07.045PubMedGoogle ScholarCrossref
Yu  S , Gao  Y , Liang  X , Huang  Y .  Acquired retinoschisis resolved after 23Gage pars plana vitrectomy in posterior microphthalmos.   BMC Ophthalmol. 2014;14:65. doi:10.1186/1471-2415-14-65Google ScholarCrossref
Godinho  G , Madeira  C , Grangeia  A ,  et al.  A novel MFRP gene variant in a family with posterior microphthalmos, retinitis pigmentosa, foveoschisis, and foveal hypoplasia.   Ophthalmic Genet. 2020;41(5):474-479. doi:10.1080/13816810.2020.1795888PubMedGoogle ScholarCrossref
Carricondo  PC , Andrade  T , Prasov  L , Ayres  BM , Moroi  SE .  Nanophthalmos: a review of the clinical spectrum and genetics.   J Ophthalmol. 2018;2018:2735465. doi:10.1155/2018/2735465PubMedGoogle ScholarCrossref
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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