Serial ERG monitoring of response to therapy in vitamin A deficiency related night blindness
- B Poornachandra ,
- Chaitra Jayadev ,
- Shama Sharief and
- Rohit Shetty
- Vitreoretina Services, Narayana Nethralaya Eye Institute, Bangalore, India
- Correspondence to Dr Chaitra Jayadev; drchaitra@hotmail.com
Abstract
Two male patients with known systemic disorders who presented with complaints of nyctalopia underwent a complete ophthalmic examination including electrophysiological evaluation and serum vitamin A (retinol) levels. A significant vitamin A deficiency was detected, supplementation started and repeat electroretinogram (ERG) testing was carried out to monitor the timeline of recovery. Restoration of rod and generalised cone function was rapid within the first week of receiving treatment and near normal recovery was seen after 1 month of supplementation. Serial monitoring of ERG changes in vitamin A deficiency (VAD) associated night blindness plays an important role to demonstrate functional recovery post-treatment. The different effects of VAD on rod and cone function, and their rate of recovery, may reflect differences in the visual cycle between the two photoreceptors. We report the serial ERG changes in VAD related night blindness secondary to intestinal lipofuscinosis and liver cirrhosis in two patients.
Background
Monitoring of electroretinogram (ERG) changes in case of vitamin A deficiency (VAD) associated night blindness pretreatment and post-treatment plays an important role to demonstrate functional recovery.
Case presentation
Both patients presented with complaints of difficulty in night vision. There was no history suggestive of hereditary retinal diseases in either of them. Patients underwent a comprehensive clinical ophthalmic examination followed by optical coherence tomography (OCT) and electrophysiological evaluation according to the International Society for Clinical Electrophysiology of Vision (ISCEV) standards at presentation. The ERG was repeated after 1 week, 1 month and 2 months of receiving vitamin A intramuscular injections, 100 000 units daily for 3 days followed by oral 50 000 units daily for 2 weeks.
Case 1
A man in his early 20s presented with visual complaints since a month. On systemic examination, he was malnourished and had a history of intestinal biopsy done with features suggestive of lipofuscinosis of the intestine (figure 1). Serum vitamin A levels were low at 0.02 mg/mL (normal: 0.3–0.6 mg/mL). On presentation, his corrected distance visual acuity was 20/30 in both eyes.
Histopathology slide-section from the small intestine showing lipofuschin deposition.
Case 2
A 50 plus man presented with complaints of blurred vision at night since a year. He was a known case of alcoholic liver disease. The serum vitamin A level was 0.02 mg/mL. At presentation his corrected distance visual acuity was 20/30 in both eyes. On slit lamp examination, the anterior segment showed grade 1 nuclear sclerosis in both eyes. On fundus examination, retinal pigment epithelium mottling was present with an altered foveal reflex in both eyes.
Investigations
Case 1
Anterior segment and fundus examination were unremarkable (figure 2). The OCT scans in both eyes were within normal limits (figure 3). At presentation, the ERG showed absent scotopic responses to dim flash dark adapted (DA) 0.01 and reduced A and B wave amplitudes for DA 3.0 and DA 10.0 tests (figure 4A). There was a significant reduction in oscillatory potential amplitudes. Reduced B wave amplitudes in light adapted (LA) 3.0 and 3.0 Hz flicker were also seen.
Fundus photo of both eyes of Case1 showing no obvious abnormalities.
Horizontal optical coherence tomography scan through the fovea of both eyes showing an intact retinal architecture (Case 1).
Electroretinogram (ERG) changes at presentation and after supplementation of vitamin A in Case 1.
Case 2
The OCT scan of both eyes showed intact retinal layers with focal changes in the retinal pigment epithelial layer in the left eye (figure 5). Full field ERG changes were similar to the first case with the ERG at presentation showing absent scotopic rod responses to dim flash DA 0.01 and reduced A and B wave amplitudes for DA 3.0 and DA 10.0 tests (figure 6A). Oscillatory amplitudes were significantly reduced with a mild delay and reduction in B wave amplitudes in LA 3.0 and 3.0 Hz flicker.
Multicolour fundus photograph and optical coherence tomography showing retinal pigment epithelium mottling (white rings) in both eyes (Case 2).
Electroretinogram changes at presentation and after supplementation of vitamin A in Case 2.
Treatment
Intramuscular vitamin A injection at 1 week, 1 month and 2 months.
Outcome and follow-up
Case 1
After 1 week of vitamin A supplementation, the ERG showed improved DA 0.01 to dim flash response reaching to almost normal levels at the end of 1 month (figure 4B,C). Both A and B wave amplitude responses in DA 3.0 and DA 10.0 were near normal at 1 month follow-up. Improvement in oscillatory potential amplitude and normal LA 3.0 and flicker amplitude was also seen after 1 month of vitamin A supplementation.
Case 2
Post-treatment, the scotopic rod response to DA 0.01 dim flash improved along with normal A and B wave responses in DA 3.0 and DA 10.0 tests within a week (figure 6B). Significant improvement in oscillatory potentials and LA 3.0 and flicker amplitude was also noted. Near normal recovery was noted at 1 month which was sustained with improvement of waveforms at 2 months (figure 6C,D).
Discussion
The ERG at presentation in our patients had the characteristic changes of vitamin A deficiency as reported in previous studies, with the cone ERG showing delayed latency.1 2 One-week post-treatment a significant improvement in the scotopic responses was noted and all ERG responses nearly normalised after 1 month. While one study describes normalisation of ERGs within 3 days of therapy,3 most other studies report a slower recovery.1 2 4 Katz et al report rhodopsin levels recovering to 30% of normal after just 1 day of supplementation in retinoid-deprived rats, which is more rapid than the normal rate of new opsin synthesis.5 In 1999, Smets and Waeben reported normalisation of all electrophysiological parameters in a patient with night blindness and optic neuropathy after biliopancreatic bypass when retested after 10 months. No cone dysfunction was reported despite the serum retinol concentration being well below normal.6
Rod involvement is seen earlier and is more extensive than cone dysfunction in vitamin A deficiency.7 The reasons for this remain obscure, although rods are known to be more dependent on the availability of vitamin A from the retinal pigment epithelium.8 Following vitamin A supplementation, some studies have reported the order of recovery of photoreceptors as cone function followed by peripheral rods and then perifoveal rods function.9 10 Cone visual pigments are more rapidly synthesised/metabolised than rod pigments, and thus with depleting supplies, cones may use available vitamin A at the expense of rods. Alternatively, cones may have better access to vitamin A stores than rods. Mata et al has recently demonstrated a novel pathway for opsin photopigment regeneration involving cone and Müller cells, which may explain the relative resistance of cones in VAD.11
Serial ERG monitoring performed in our cases gave evidence of the rate of electrophysiological and, therefore, functional recovery. We, however, did not perform pattern ERG and contrast sensitivity assessment. This rapid recovery of electrophysiological parameters possibly indicates early detection and treatment. In those with no palpable response at 1 week postsupplementation, the underlying cause may not be attributable to VAD alone. Treatment of VAD is simple and effective and should be considered for patients with a history of conditions leading to malabsorption of fat-soluble vitamins presenting with visual symptoms.
Learning points
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Serial monitoring of electroretinogram changes in case of vitamin A deficiency associated night blindness can play an important role to demonstrate functional recovery post-treatment.
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Rapid recovery of electrophysiological parameters possibly indicates early detection and appropriate treatment.
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If there is no detectable response or improvement at 1 week postsupplementation, the underlying cause needs to be reinvestigated.
Ethics statements
Patient consent for publication
Footnotes
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Contributors PBG and CJ contributed to planning, conducting and reporting of the work. SS and SGG contributed to conducting and reporting of the work. All coauthors have agreed to be listed as authors in the work and have agreed to the contributorship statement prepared by the corresponding author. PBG is the guarantor of this manuscript and accepts full responsibility for the finished work and/or the conduct of the study, has access to the data and controls the decision to publish.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.
References
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