Case of the Month

Edited by Robert N. Johnson, MD

June, 2017

Presented by Ananda Kalevar, MD

A 41-year-old woman presents with blurred vision in both eyes

Figures 1A and B: Wide-field color photographs of the right and left eye with detailed view of each macula. Note the punctate white flecks present through out the entire retina.

Case History

A 41-year-old woman presents with blurred central vision and nyctalopia in both eyes for several years.  Her past medical history was relevant for hypothyroidism and appendectomy.  Her past ocular history, family history, social history and medications were non-contributory.

On examination, best-corrected visual acuity was 20/25 in both eyes.  Intraocular pressure was normal in both eyes.  The anterior segment examination was unremarkable.  The posterior segment exam of both eyes was remarkable for extensive  deep, white, round retinal flecks (Figures 1A, 1B and insets).  Wide-field fluorescein angiography of both eyes reveals widespread punctate areas of hyperfluorescence and mild staining (Figures 2A, 2B).  Widefield fundus autofluorescence (not shown) of both eyes revealed mild hyperautoflourescence corresponding to the white lesions.  Spectral domain OCT (SD-OCT) of both macula reveal an unremarkable retinal contour with a few hyperreflective lesions in the outer retina, with some mild retinal pigment epithelium changes temporal to the fovea in the right eye (Figures 3A, 3B).  SD-OCT taken at the level of the vascular arcade in both eyes reveal numerous deep hyperreflective lesions (Figure 4A, 4B).  En-face structural SD-OCT at the level of the photoreceptors reveals widespread hyperreflective dots, sparing the fovea (Figures 5A, 5B).

Electroretinography (ERG) studies were performed to evaluate for congenital stationary night blindness.  The ERGs were performed initially in a dark-adapted eye previously occluded and then repeated after light exposure to assess for a significant change in tracings.  Comparing both settings, in the light adapted setting, severe abnormalities in the rod-specific tracings were present and combined rod and cone-specific tracings showed reduction in the A-waves.

Genetic sequencing revealed a mutation in the coding sequence of the RDH5 gene.

Figures 2A and B: Wide-field fluorescein angiography of the right and left eye. Wide spread area of punctate hyperfluorescence are present in each eye. Irregular fluorescence is noted in each macula due to retinal pigment epithelial alterations.

Figures 3A and B: SD-OCT of both macula. Note the presence of a few hyperreflective spots arising from the RPE and extending into the ellipsoid zone.

A

B

Figures 4A and B: SD-OCT of the right eye superior to the macula, and the left eye inferior to the macula. Note the multiple discrete hyperreflective protrusions extending from the RPE into the outer retina.

Figures 5A and B: En Face SD-OCT of the right and left macula shows the extensive flecks in both eyes.

What is your Diagnosis?

Differential diagnosis

Fundus flavimaculatus, familial dominant drusen, retinitis pigmentosa albescens, pattern dystrophy, Bietti’s crystalline dystrophy, fleck retina of Kandori, benign fleck retina, enhanced S cone, hyperoxaluria, cystinosis, tamoxifen retinopathy, talc retinopathy, Vitamin A deficiency.

 

Discussion

Fundus albipunctatus (FA) is a rare autosomal recessive form of congenital stationary night blindness, that is characterized by numerous white punctate lesions scattered throughout the retina, sparing the fovea.1-4  FA is part of a heterogenous group of flecked retina syndromes.  Patients may experience night blindness or remain asymptomatic until the striking clinical appearance is seen.

 Optical coherence tomography (OCT) studies demonstrated small dome-shaped hyperreflective deposits that originate from the retinal pigment epithelium (RPE) and project into the outer retina causing disruption to the outer layers.3  Fundus autofluorescence similarly revealed areas of hyperautoflourescence that corresponded to these lesions seen on OCT and fundus examination.3

 Electroretinogram studies demonstrate usually unremarkable photopic responses and scotopic responses are markedly affected but can have regeneration of responses after prolonged dark adaptation.1-3  This can help differentiate FA from retinitis punctata albescens and other entities.

 Fundus albipunctatus is primarily caused by mutations that affect 11-cis retinal dehydrogenase (RDH) which is located in the RPE.1  It is hypothesized that disruption of the production of 11-cis retinal causes accumulations of retinoids which can represent the white lesions seen on exam.  There have also been reports of FA occurring secondary to a mutation in RPE65.

 

Take Home Points

  • FA is a form of congenital stationary night blindness
  • FA is a rare member of the flecked retina differential
  • Majority of FA is caused by RDH mutations.

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References:

  1. Ryan S.  Retina, 5th ed.  2013:  904-906.
  2. Skorczyk-Werner A, Pawłowski P, Michalczuk M, Warowicka A, Wawrocka A, Wicher K, Bakunowicz-Łazarczyk A, Krawczyński MR. Fundus albipunctatus: review of the literature and report of a novel RDH5 gene mutation affecting the invariant tyrosine (p. Tyr175Phe). Journal of applied genetics. 2015 Aug 1;56(3):317-27.
  3. Genead MA, Fishman GA, Lindeman M. Spectral-domain optical coherence tomography and fundus autofluorescence characteristics in patients with fundus albipunctatus and retinitis punctata albescens. Ophthalmic genetics. 2010 Jun 1;31(2):66-72.
  4. Adel FA, Lopez I, Khan A, Koenekoop R, Racine J, Basheikh A. Fundus Albipunctatus: A Novel Mutation. Ann Clin Case Rep. 2016; 1.;1135.

Comments or Questions

Fundus albipunctatus (FA) is a rare autosomal recessive form of congenital stationary night blindness, that is characterized by numerous white punctate lesions scattered throughout the retina, sparing the fovea.  FA is part of a heterogenous group of flecked retina syndromes.  Patients may experience night blindness or remain asymptomatic until the striking clinical appearance is seen.

 Optical coherence tomography (OCT) studies demonstrated small dome-shaped hyperreflective deposits that originate from the retinal pigment epithelium (RPE) and project into the outer retina causing disruption to the outer layers.  Fundus autofluorescence similarly revealed areas of hyperautoflourescence that corresponded to these lesions seen on OCT and fundus examination.

 Electroretinogram studies demonstrate usually unremarkable photopic responses and scotopic responses are markedly affected but can have regeneration of responses after prolonged dark adaptation.  This can help differentiate FA from retinitis punctata albescens and other entities.

 Fundus albipunctatus is primarily caused by mutations that affect 11-cis retinal dehydrogenase (RDH) which is located in the RPE.  It is hypothesized that disruption of the production of 11-cis retinal causes accumulations of retinoids which can represent the white lesions seen on exam.  There have also been reports of FA occurring secondary to a mutation in RPE65.