FP856 : Retinal Structural and Metabolic Alterations in Parkinson’s Disease.

Dr. Karen Sharma, S17101, Dr. Ashwin Mohan, Dr. Rohit Shetty

Introduction

Parkinson’s disease is a progressive neurodegenerative disorder. It affects people in the elderly age group with a prevalence of seven to 10 million individuals worldwide ¹. It is characterized by loss of dopaminergic neurons in the nigrostriatal pathway in the brain leading to  motor impairments and deficits like bradykinesia, postural rigidity and  non-motor symptoms like  depression, memory loss, visual hallucinations. ² There is evidence that  dysfunction occurs at various levels in the visual pathway in addition to disorders of cortical visual processing. The disruption of retinal structure and function could present as pscyhophysical, electrophysiological and morphological changes.³   

Oximetry is a non invasive method of determining the oxygen saturation in the retinal vessels. It is based on the principle of differential absorption of light by haemoglobin at different wavelengths which is determined using photospectrometry. ⁴

 Aim

To investigate the association of retinal structural (peripapillary retinal nerve fiber layer (PRNFL) and macular thickness) and functional parameters (vascular oxygen saturation) with clinical scores and medication dosage in patients with Parkinson’s disease.

Methods

A cross sectional observational study of 22 eyes of 11 MRI confirmed patients with Parkinson’s Disease(PD) on treatment was undertaken in a tertiary care hospital in South India.  The study protocol and consent forms were approved by the institutional review board. Written informed consent was obtained from each subject in accordance with the Helsinki Protocol.. Study specific procedures included PD severity assessments, comprehensive ophthalmological examinations, and performance of OCT and retinal Oximetry.

Parkinson’s Disease  –

The patients underwent a neurological evaluation to categorize the severity of PD, using the Motor Subscale (Part 3) of the Unified Parkinson’s disease rating scale (UPDRS III) and modified Hoehn and Yahr scale (HY). a measure of both impairment and disability that ranges from 0 (no visible symptoms of PD) to 5 (wheelchair bound or bedridden unless aided)^5,6

These assessments were made without knowledge of the ophthalmological findings.

Duration of the disease and use of medications including the equivalent daily dosage of levodopa was recorded.

EYE –

Patients with corrected distance visual acuity less than 6/9, unclear media like corneal opacity or cataract,  glaucoma, primary retinal pathology like diabetic or hypertensive retinopathy or uveitis were excluded.

The examination consisted of –

• corrected distance visual acuity was measured in Snellen’s and the converted to ETDRS letters.
• Intraocular pressure was measured using applanation tonometry.
• A slit lamp biomicroscopy examination was performed by a trained ophthalmologist.
• Fundus evaluation was performed after full pupillary dilataion following instillation of tropicamide with phenylephrine; using 90D slit lamp biomicroscopy and 20 D indirect ophthalmoscopy.

 

Additional tests performed were –

• Optical coherence tomography to measure peripapillary nerve fibre layer thickness (PRNFL) and macular thickness (Spectralis, Heidelberg, Germany)
• Retinal oximetry (Oxymap T1, Oxymap HF, Reykjavik Iceland) to measure the diameter of the arteries & veins, the oxygen saturation and the difference in oxygen saturation.

STATISTICAL ANALYSIS

RESULTS

Demographics –

• The average age of the patients was 2years (95% CI – 53.4-59.0), age of onset of disease was 50.8 years (95% CI – 47.7-53.9), duration of disease was 5.1 years (95% CI – 3.7-6.5),

Parkinson’s Disease related parameters – drug/clinical scores-

• UPDRS III score was 9(95% CI – 25.1-30.7), H&Y score was 2.2 (95% CI – 2.1-2.4) and Levodopa equivalent dosage per day was 626(95% CI – 532.8-719.2)

Oximetry –

• The arteriolar diameter was 3µm (95% CI – 107.9-118.7), venous diameter 152.4 µm (95% CI – 147.7-157.1)
• The arterial saturation was 5% (95% CI – 94.3-100.9), venous saturation 60.1% (95% CI – 58.2-61.9), AVSD was 37.5% (95% CI – 34.4-40.6)

Correlations –

• The H&Y score correlated negatively with the age of onset (r=-459, p=0.048), positively with the UPDRS score (r=0.623,p=0.002), and Levodopa dosage (r=0.671,p=0.001)
• The arteriolar saturation correlated inversely with Levodopa dosage (r=554,p=0.011) while positively with AVSD (r=0.840,p<0.001)

DISCUSSION

The retina is a neuroectodermal tissue. There are embroyological and anatomical similarities in the vasculature of the eye and brain. The retina is the only tissue in the body where non invasive visualization of  vasculature is possible.The possibility of predicting cerebral pathology with respect to alterations in the vascular functioning of the retina has been explored.⁷

Dopaminergic neurons are present in the inner nuclear layer of the retina. They are a type of amacrine cells called A18. ⁸ They are depolarized by light onset – under both scotopic and photopic conditions, implying input from depolarizing bipolars of both rod and cone varieties.

1. Harnios et al examined the levels of dopamine in the retinae of Parkinson’s patients after death. Three patients who had not received dopamine till five days before death had lesser dopamine levels as compared to the five patients who had received dopamine 12 -15 hours before death. They concluded that retinal dopamine levels were in direct correlation with systemic dopamine levels.⁹

The possibility of retinal vascular functioning acting as an indicator of systemic control in patients with Parkinson’s disease is a new avenue and needs further research.

REFERENCES

1. de Lau LM et al Epidemiology of Parkinson’s disease. Lancet Neurol 2006; 5: 525–35
2. Fenelon G et al Hallucinations in Parkinson’s disease: prevalence, phenomenology and risk factors. Brain 2000; 123: 733–45.
3. Archibald NK et al. The retina in Parkinson’s disease. Brain. 2009 Mar 31;132(5):1128-45.
4. (Hardarson SH, Harris A, Karlsson RA, Halldorsson GH, Kagemann L, Rechtman E, et al. Automatic Retinal Oximetry. Invest Ophthalmol Vis Sci 2006; 47: 5011–5016.
5. Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations.
6. Goetz CG et al, Movement Disorder Society Task Force on Rating Scales for Parkinson’s Disease
7. (London A., Benhar I., Schwartz M. The retina as a window to the brain from eye research to CNS disorders. Nat Rev Neurol. 2011;9:44–53.).
8. Frederick JM, Rayborn ME, Laties AM, Lam DM, Hollyfield JG. Dopaminergic neurons in the human retina. J Comp Neurol 1982; 210: 65–79
9. Harnois C, Di Paolo T. Decreased dopamine in the retinas of patients with Parkinson’s disease. Investigative ophthalmology & visual science. 1990 Nov 1;31(11):2473-5.