The Role Of Ophthalmology On Early Detection of Alzheimer’s Disease

The Role Of Ophthalmology On Early Detection of Alzheimer’s Disease

September 23, 2021

Ophthalmology News - “The word ophthalmos, “οφθαλμος”  from which the term ophthalmology is derived, appears often in Homer’s epic poetry: “Athena aimed the arrow towards the nose, near the ophthalmos [eye] and pierced the white teeth” [Il 5.291].”

Diagnosing Alzheimer’s is a currently a challenge. Some techniques can detect signs of the disease but are impractical for screening millions of people.

Because the retina is connected to the brain by way of the optic nerve, researchers believe that the deterioration in the retina and its blood vessels may mirror the changes going on in the blood vessels and structures in the brain, thereby offering a window into the disease process

Optical coherence tomography angiography (OCTA) enables physicians to see the smallest veins in the back of the eye, including the red blood cells moving through the retina.  

The detection of the plaques in the retina early in the disease, before the onset of dementia or very early in the course of the disease, and examination with fundus autofluorescence (FAF) and OCT is extremely important and may be a valuable supplement to neurological testing.

Alzheimer’s disease (AD) is the most common cause of dementia. A recent meta-analysis showed that in AD patients, there was a significant RNFL thickness reduction compared with healthy subjects. Controversy exists about the correlation between RNFL measurements and the severity of the dementia.

In addition to RNFL thinning, choroid, macular and GCL thickness are also reduced even without visual failure.

Patients with Alzheimer's disease demonstrate severe deficits in memory with cortical features of language difficulty and visuomotor spatial deficits. They also may present with psychotic symptoms of delusions and hallucinations, and personality and behavioral changes.

Advancing age, genetics, and environmental risk factors are important in the development of Alzheimer's disease. Visual abnormalities have been described in Alzheimer's disease and may be related to the development of visual hallucinations.

Ophthalmic News -  Inflections of Vision-Illumination-Emanation! Intersection of the energies streaming from the infinite dimensions and intelligent infinity. 

Signs and symptoms of Alzheimer’s disease in the retina, optic nerve and the more posterior afferent visual system in the temporal and parietal lobes may point physicians to a diagnosis of Alzheimer’s disease earlier than previously realised.

The importance of being aware of the—often—subtle signs and symptoms in patients 55 years and older. With diseases such as Alzheimer’s and Parkinson’s, patients may present first to an ophthalmologist rather than a neurologist because of the associated visual disturbances.

A Case

Pearls gleaned from a case, a 68-year-old man who presented with progressive field constriction for 2 years and the inability to drive at night for approximately 1½ years.

The patient described seeing oncoming lights when driving as starbursts. Constricted visual fields may be an initial presentation of possible Alzheimer’s disease.

Ophthalmology News - Inflections of Vision-Illumination-Emanation! Intersection of the energies streaming from the infinite dimensions and intelligent infinity. 

However, the differential diagnosis is large and includes retinal degenerations; quinine toxicity; central retinal artery occlusion; end-stage glaucoma or papilloedema; confluent optic disc drusen; bilateral occipital lobe infarctions; non-physiological response; and cognitive impairment on automated perimetry.

The visual field constriction implicates a visual field defect in the retina, optic nerve or occipital lobe; the photophobia, a problem in the retina; and night blindness and depth perception, a retinal or cortical issue.

Consideration of the three locations suggests that there may be more of a retinal or a cortical problem, or both. Alzheimer disease affects them all: i.e., the retina, optic nerve and the visual system posterior to the lateral geniculate.

The patient’s history was positive for prostate cancer and basal and squamous cell cancers, without metastases; hypertension; and hyperlipidaemia.

Ophthalmology News - “The word ophthalmos, “οφθαλμος”  from which the term ophthalmology is derived, appears often in Homer’s epic poetry: “Athena aimed the arrow towards the nose, near the ophthalmos [eye] and pierced the white teeth” [Il 5.291].”

A rule to live by in neuro-ophthalmology is to determine if the patient’s problem at hand is caused by the cancer recurrence, especially with breast cancer, or cancer therapy.

The patient’s ocular examination was unremarkable, with 20/40 vision bilaterally. Interestingly, the patient could see only the test Ishihara plate, although he had no history of colour blindness. The acquired loss of colour vision could be in the cones, optic nerve or cortical system.

This provides a subtle hint of an afferent visual problem. Colour vision measures contrast sensitivity. Using low-contrast visual acuity [VA], a deficit worse than 20/40 might be identified.

Optical coherence tomography imaging was unremarkable but showed slight flattening, with the fovea-macular contour slightly broadened. Fundus autofluorescence also showed no striking abnormality suggestive of early Alzheimer’s disease.

Multifocal electroretinography (ERG), however, showed an almost isoelectric tracing in the right eye despite 20/40 vision. In the left eye, multifocal ERG abnormalities were present but was not as pronounced as in the right eye.

Cranial MRI showed both non-specific changes and that paraneoplastic autoantibodies and the lumbar puncture cerebrospinal fluid profile were negative.

Automated perimetry showed an inferior quadrantanopia in the left eye and a more subtle defect in the right eye. This localisation pattern was in the right parietal temporal lobe.

From this testing, we know that this patient has brain disease in the right parietal temporal lobe. The multifocal ERG results indicated the presence of retinal disease. This proved to be an extensive process in the visual system.

In addition to the constricted visual fields, colour vision deficit and abnormal ERG, the patient’s history showed dissatisfaction with the results of cataract surgery despite 20/40 bilateral VA and a depth perception of only 40 seconds of arc.

One reason for dissatisfaction postoperatively with a good Snellen VA may be Alzheimer’s disease. The root of the dissatisfaction may be subtle problems with difficulty reading and finding words and mild short-term memory loss.

Other clues are that the patient never arrived alone at appointments and often did not answer questions.

Ophthalmic News -  Inflections of Vision-Illumination-Emanation! Intersection of the energies streaming from the infinite dimensions and intelligent infinity. 

Potential Presentations

Patients who present with predominantly visual symptoms may have posterior cortical atrophy.

However, the patients who present with mildly disrupted memory and functioning may have a more global deficit of visual processing, e.g., a progressive decline in visuospatial, visual perception and literacy skills, which can appear in patients who are on average 50 to 65 years of age.

Experts disagree about whether posterior cortical atrophy is a pure form of Alzheimer’s disease or a separate entity. Lewy body dementia and prion disease may also have similar visual symptoms.

The presentations of Alzheimer’s disease include the unhappy patient with good VA after cataract surgery and, in patients who have not had recent cataract surgery, loss of colour vision, loss of depth perception and photoreceptor dysfunction manifesting as glare and night blindness.

Physicians should be alert to patients with visual field defects who have trouble with the automated perimetry test, especially with repeated attempts. Patients may also present with a homonymous hemianopsia but a normal MRI scan.

This clinical presentation should alert ophthalmologists and neurologists to the possibility of Alzheimer’s disease.

When such patients present, Alzheimer’s disease should be suspected. Hopefully, during 2022 some treatments will become available.

As with most treatments, they will work better the sooner they are instituted before the disease destroys most of the brain and a large segment of the retinal and optic nerve function.

Ophthalmologists may be the key to get the diagnostic process moving. The multifocal ERG may be the most sensitive test to identify retinal abnormalities in patients with dementia syndromes.

Ophthalmology News - Inflections of Vision-Illumination-Emanation! Intersection of the energies streaming from the infinite dimensions and intelligent infinity. 

Let's Check What Others Think & Say