Issue 5: Fundus Albipunctatus (December 2011)

Welcome

Professor Michael Kalloniatis, Director
We are delighted to tell you about a new five-year research project to take place at Centre for Eye Health (CFEH).

The National Health and Medical Research Council (NHMRC) has awarded $1.1 million to a multidisciplinary team of optometrists, ophthalmologists, visual scientists and public health experts who will utilise CFEH referral information and clinical data to explore the effectiveness of various models for managing glaucoma in the future.

The ultimate aim is more cohesive patient management, improved quality of life for people affected by glaucoma and a reduced economic burden of eye disease.

A partnership project with Guide Dogs NSW/ACT and The University of New South Wales (UNSW), the research team will investigate current glaucoma practices including the quality of clinical diagnosis and referrals, the appropriate utilisation of technology, and the integration of complementary facilities and services.

The NHMRC Glaucoma Guidelines highlight the need for appropriate and timely referral of patients at-risk of developing glaucoma. As optometrists, we are usually the primary eye-care provider, and as such are well-placed to help the overloaded health system by appropriately triaging patients – especially now that CFEH is here to provide extra resource capacity in the form of ocular imaging and clinical expertise. I look forward to sharing more about this research project with you in the future.

Prof. Michael Kalloniatis

Centre Director

CENTRE UPDATE

  • More than 8,700 referrals have been received to date.
  • Over 45,000 occasions of service (individual tests) have been performed.

In the last three months:

  • CFEH consultant ophthalmologists provided advice on 19% of clients;
  • 17% of clients were from Western Sydney;
  • 9% of clients were from regional areas.

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Case Report

Fundus Albipunctatus
Figure 1: Fine hard drusen are hardly noticeable with the fundus photo (left eye).
Figure 1: Fine hard drusen are hardly noticeable with the fundus photo (left eye).
Julie, a 52-year-old female, was referred to CFEH because of deteriorating central vision. She had previously been diagnosed with an inherent retinal condition causing abnormal dark adaptation, and it was thought that her progressive visual disturbance may be due to the condition fundus albipunctatus.

Issues to consider

1. What is fundus albipunctatus?

2. What initial clinical tests should be considered?

3. What additional tests can evaluate her retinal function?

4. How might the patient be counselled?

Results and Discussion

Julie has had poor night vision for some time, but has adapted and copes well. Her paracentral visual fields, however, have gradually worsened and she is now concerned about losing her central vision completely. Visual acuities were 6/6 in the right eye and 6/4.8 in the left eye.

On examination at CFEH, static visual field testing showed a paracentral scotoma extending from the blind spot and covering regions between five to 15 degrees from fixation (Figure 2A).

Similar visual loss was present in the other eye. Peripheral visual field using Goldman kinetic showed near-normal visual field in both eyes (Figure 2B). Fundus examination/photography and Optomap imaging revealed multiple pale dots, most notably in the paramacula and posterior pole regions, extending to the midperiphery (Figure 1). Denser dots were present in the superior fundus of each eye.

Figures 2A and 2B: Left eye visual fields show paracentral field loss (A) and full kinetic field (B).
Figures 2A and 2B: Left eye visual fields show paracentral field loss (A) and full kinetic field (B).
Figures 2A and 2B: Left eye visual fields show paracentral field loss (A) and full kinetic field (B).

Spectralis optical coherence tomography (OCT) imaging revealed a disorganised photoreceptor layer, and a relatively attenuated retinal pigment epithelium (RPE) layer with subretinal deposits between the two layers. OCT imaging through the pale patches suggested atrophy of the deeper retinal layers (Figure 3).

Figures 3A and 3B: OCT Spectralis scanning laser ophthalmoscope (SLO) imaging of the left eye showed discolouration of the retina (A) and the OCT image sho ws disruption of the photoreceptors invagination as circled in the cross-section (B).
Figures 3A and 3B: OCT Spectralis scanning laser ophthalmoscope (SLO) imaging of the left eye showed discolouration of the retina (A) and the OCT image sho ws disruption of the photoreceptors invagination as circled in the cross-section (B).
3A and 3B: OCT Spectralis scanning laser ophthalmoscope (SLO) imaging of the left eye showed discolouration of the retina (A) and the OCT image sho ws disruption of the photoreceptors invagination as circled in the cross-section (B).

To investigate Julie’s visual status further, CFEH undertook a number of electrophysiological tests. Both eyes were tested and similar results obtained, so the results from one eye are discussed here.

Full-field electroretinogram (ERG), was performed to investigate the rod photoreceptor response. After 20 minutes of dark-adaptation, there was minimal response after light stimulation (Figure 4).

After seven minutes of light-adaptation, a response was measured in the cone photoreceptors, although its amplitude was low relative to agematched data (Figure 5).

Figure 4: Full-field ERG, with 20-minute and 10-hour dark-adaptation, shows that rod photoreceptor response depends on the duration of dark-adaptation.
Figure 5: Full-field ERG, with seven minute lightadaptation and 30 Hz response, demonstrates reduced cone photoreceptor response.
Figure 4: Full-field ERG, with 20-minute and 10-hour dark-adaptation, shows that rod photoreceptor response depends on the duration of dark-adaptation.
Figure 5: Cirrus OCT results show a thinning of the RNFL in the superior quadrant of the left eye.

The pattern ERG showed minimal response to the contrast reversing stimulus, suggesting sub-optimal operation of the retinal ganglion cells (Figure 6).

Figure 6: Pattern ERG shows minimal retinal ganglionic response.
Figure 6: Pattern ERG shows minimal retinal ganglionic response.

The multifocal ERG of the left eye showed central as well as peripheral depression of response. This indicated that cone photoreceptors were operating at a sub-standard level (Figure 7).

Figures 7A and 7B: Multifocal ERG shows the patient’s cone photoreceptor response is reduced centrally (A) compared with a normal result (B).
Figures 7A and 7B: Multifocal ERG shows the patient’s cone photoreceptor response is reduced centrally (A) compared with a normal result (B).
Figures 7A and 7B: Multifocal ERG shows the patient’s cone photoreceptor response is reduced centrally (A) compared with a normal result (B).

After a prolonged dark-adaptation of more than 10 hours, the scotopic ERG was repeated for the left eye and the response was normal (Figure 4). This result indicates that rod photoreceptors are functional but require extensive periods of dark-adaptation, a trait which is characteristic of fundus albipunctatus.

Similar outcomes have been found in other patients with fundus albipunctatus, with one study(1) reporting that 38% of cases were associated with late onset cone dysfunction, suggesting that the loss of function may be progressive in both rod and cone photoreceptors.

Care should be taken in classifying congenital stationary night blindness as fundus albipunctatus because central vision is also affected in other conditions such as retinitis albescens or enhanced S-cone syndrome.

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Spotlight On: Fundus Albipunctatus and Congenital Stationary Night Blindness (CNBS)

Fundus albipunctatus, an autosomal recessive disorder, is a form of congenital stationary night blindness (CSNB)(1).

The condition has been attributed to a defect in the RDH5 gene, which is encoded with 11-cis retinol dehydrogenase, and is located in the retinal epithelia. The RDH5 gene is critical for regenerating visual pigment.

Patients with fundus albipunctatus often have a long-standing history of night blindness, presenting with white-yellow retinal deposits (though this can also be attributed to retinitis puntata albescens or enhanced S-cone syndrome).

Prolonged dark-adaptation of more than two hours will cause the retinal electrophysiological response of patients with fundus albipunctatus to reach normal levels. This is not the case in other forms of CSNB(2).

In addition to visual function and imaging of the retina, electrophysiology can assist in diagnosing fundus albipunctatus.

CSNB, the broader condition, is categorised into two groups. Group 1 has normal fundal appearance whilst Group 2 has abnormal white flecks and discolouration in the retina.

The associated pattern of inheritance of Group 1 can either be X-linked, autosomal recessive or autosomal dominant. Many of the genes responsible for the phenotype have been identified(3), enabling molecular testing to detect the gene.

Patients with CSNB may initially present with low visual acuity, nystagmus and poor night vision. When stimulated with a single flash of light during a dark-adapted state, the typical ERG response of CSNB with a normal fundus is a small b-wave and normal a-wave forming a negative b-wave configuration (see Electroretinogram Equipment Profile insert for more information). In some cases of CSNB, cone photoreceptors are also affected.

In animal models, light and Vitamin A have been shown to cause an accumulation of A2E, which is important for the regeneration of II-cis retinal. Defects in its transport, however, can lead to the production of lipofuscin and is also linked to aged-related macular degeneration (ARMD).

Currently, there is no effective treatment, although patients should be warned against excessive light exposure and vitamin A supplements, and informed that they may find comfort wearing sunglasses. Decreasing light levels during retinal examinations will also considerably increase patient comfort.

Effective communication is essential when managing patients with rod disorders associated with cone dysfunction.

Genetic counselling can also be of use, helping patients in family planning decisions, or to adapt and prepare for impending lifestyle or career changes*.

Patients are likely to experience deteriorating visual acuity over time, and may need to be eferred to a specialist provider of orientation and mobility support, such as Guide Dogs NSW/ACT (02) 9412 9300.

* www.genetics.edu.au/services/counsel

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TEST PROFILE

Full-field Electroretinogram (fERG)

Full-field ERG

Figure 8: Full-field Electroretinogram (fERG)
Since 1865, electrical activity has been recorded in response to light on the retina. Our understanding has expanded from full field electroretinography (Figure 1), to now include spatial electrical responses from the retina useful in assessing central vision.

Electroretinography has expanded our understanding of both normal and diseased visual systems, providing important diagnostic information. This profile focuses on full-field electroretinography, sometimes referred to as the flash electroretinogram (flash ERG).

The flash ERG is a gross electrical potential with the amplitude of the response dependent upon the number of functioning cells(2,3).

Click here for full profile >>

See entire equipment list for the Centre >>

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References

  1. Makoto N., Hotta Y., Tanikawa A., Terasaki H., and Miyake Y., A high association with cone dystrophy in fundus albipuntatus caused by mutations of the RDH5 gene. Invest Ophthalmol Vis Sci. 2000; 41:3925-3932
  2. Genead M., Fishman G., and Linderman M., Spectral-domain optical coherence tomography and fundus autoflourescence characteristics in patients with fundus albipuntatus and retinitis puntata albescens.Opthal Gen. 2010; 3(2): 66-72.
  3. Mata N., Weng J., and Travis G., Biosynthesis of major lipofuscin flourophore in mice and humans with ABCR-mediated retinal and macular degeneration. Proc Natl Acad Sci USA. 2000; 97(13): 7154-7159.
  4. Carr R. Congenital stationary nightblindness. Trans Am Ophthalmol Soc. 1974; 72:448-487
  5. Mamor M., Fulton A., Holder G., Miyake Y., and Brigell M., ISCEV standard for full-field clinical electroretinography (2008 update). Doc Ophthalmol 2009; 118: 69-77.
  6. Niwa Y., Kondo M., Ueno S., Nakamura M., Terasaki H., and Miyake Y., Cone and rod dysfunction in fundus albipuntatus with RDH5 mutation: an electrophysiological study. Invest Ophthalmol Vis Sci. 2005; 46(4):1480-1485.

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Disclaimer: This newsletter is not intended to provide or substitute advice through the appropriate health service providers. Although every care is taken by CFEH to ensure that this newsletter is free from any error or inaccuracy, CFEH does not make any representation or warranty regarding the currency, accuracy or completeness of this newsletter.

Copyright: © 2011, Centre for Eye Health Limited. All images and content in this letter are the property of Centre for Eye Health Limited and cannot be reproduced without prior written permission of the Director, Centre for Eye Health Limited.

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