Retinal Disease and Psychological Disorders: A Literature Review

A look at psychiatric medications that may yield unexpected ocular benefits, plus advice on how to spot depression in those with visual loss.

Robert Murphy, CONTRIBUTING EDITOR

Retinal disease and mental disorders, from mild to severe, have coexisted from the very beginning. Associations between the two, especially cases involving visual loss and depression, remain prevalent.

From a psychosocial perspective, impending vision loss with a concomitant decrease in quality of life may well occasion episodes of despair to the point of full-blown major depression and coexistent heightened anxiety. From a pharmacologic and toxicologic perspective, there remain the murky risks of ocular complications or, conversely, the hope and potential promise of therapeutic benefits from the use of systemic psychiatric and other psychotropic medications, both legitimate and illicit, which these days Americans consume in expanding numbers.

The two reports outlined below convey vivid portraits of the latter scenario. Other data compiled here make the case for attending not only to the ocular health of patient but also to their overall well-being and mental fitness, particularly those patients progressing into advanced years.

PSYCHIATRIC MEDS AND RETINAL DISEASE

Psychiatric medications normally prescribed for major depression or bipolar disorder, as well as other mental disorders, may provide therapeutic benefits for patients with certain refractory retinal diseases. Two such instances nicely exemplify a fortuitous psychopharmacologic/retinal-therapeutic dynamic.

• Aripiprazole (Abilify, Bristol-Myers Squibb) and Charles Bonnet syndrome. A 2011 case report in the journal Psychogeriatrics chronicles a 70-year-old female who suffered from complex hallucinations with left homonymous hemianopsia associated with right occipital lobe infarction, or Charles Bonnet syndrome.¹

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Named for the Swiss naturalist and philosopher who observed its symptoms in his 87-year-old grandfather and first described the condition in 1760,² Charles Bonnet syndrome is characterized by visual hallucinations without a change of consciousness or cognition.¹

Numerous causes may be responsible for the onset of Charles Bonnet syndrome, including central and peripheral nervous system lesions and ocular disorders. Most patients experience the hallucinations following acute visual loss, owing to deafferentation along the visual pathway in the acute period. Specifically, neurons of the visual-association cortices, located in the occipital and inferior-lateral temporal lobe, attempt to adapt through hypersensitivity to in coming stimuli, which is thought to trigger hallucinations.³

In this case, the patient presented with four key findings characteristic of Charles Bonnet : (1) recurrent, formed, complex visual hallucinations of people and animals; (2) awareness that the images were not real; (3) absence of delusional ideation and (4) no cognitive impairment.

In some patients, the hallucinations cease without intervention if the triggering cause, such as A cataract, is re solved.^4,5 For those deeply disturbed by the vivid hallucinations, however, neuroleptic medications may be indicated, not only promptly to reduce the hallucinations but also to relieve the anxiety that often accompanies such episodes.⁶ These have included antipsychotics such as risperidone, olanzapine, and haloperidol, all of which are available only as generics. Anti convulsants and certain antidepressants have also been used to bring about limited improvement.^4,6

In this case, aripiprazole, an antipsychotic agent approved in 2002, reduced immediately the patient's anxiety while the hallucinations faded progressively over four weeks. Aripiprazole works as a dopamine D2 partial agonist, a partial agonist at the serotonin 5-HT1A receptor, and an antagonist at the 5-HT2A receptor. A recent study found that its anxiolytic effect may be associated with its partial agonistic effect on the 5-HT1A receptor.⁷

Although first described 252 years ago, Charles Bonnet syndrome remains underdiagnosed.⁸ And because its symptoms are often self-limited, practitioners may downplay the need for treatment.^4,6 Even so, distressed patients may seek psychiatric, neurological or ophthalmological services. It's therefore important that ophthalmologists remain vigilant for the syndrome's characteristic features and be prepared to initiate a course of intervention perhaps involving off-label use of the antipsychotic medication aripiprazole.

• Valproic acid and retinitis pigmentosa. A 2011 retrospective chart review described the therapeutic potential of the anticonvulsant and mood stabilizer valproic acid prescribed off-label for patients with retinitis pigmentosa.⁹

The clinicians examined 13 eyes of seven patients before and after brief treatment (average: four months) with valproic acid at a dose roughly 60% lower than that typically used to treat epilepsy. Nine eyes of five patients achieved improvements of visual field, while two eyes exhibited no change. The overall increase in visual field was 11%. Given the typical visual field loss associated with retinitis pigmentosa, these gains were considered clinically significant.

Patients also experienced average improvements in Snellen visual acuity from 20/47 to 20/32; this too was considered clinically significant. The side effects were mild and well tolerated.⁹

Widely used as an anticonvulsant and mood stabilizer, valproic acid's efficacy for these indications is thought to come from its effect on gamma-aminobutyric acid (GABA) levels through glutamic acid decarboxylase and GABA transaminase modulation.^10,11 Elsewhere, clinicians have reported limited delays of photoreceptor loss in RP patients with the use of nutritional supplements such as vitamin A, as well as hyperbaric oxygen therapy.^12,15

Given that retinitis pigmentosa is a blinding disease with no optimal treatment options, the gains in visual field among five of the seven patients examined here following treatment with valproic acid is a promising development. Keep in mind that this chart review involved only seven patients with a relatively brief follow-up period, on average four months.

Still, it's hardly a stretch to speculate that valproic acid may offer an exciting new potential therapy for RP. The results of this preliminary study coupled with prior in vitro data suggest that valproic acid may effectively forestall photoreceptor loss associated with the disease.⁹

VISION LOSS AND DEPRESSION

The literature contains a wealth of data underscoring the association of visual loss and major depression. The psychosocial impact of visual loss associated with age-related macular degeneration and other blinding diseases takes a severe toll on patients' quality of life. Retinal specialists should be prepared to spot the signs and symptoms of major depression (see Table 1) and perhaps refer the patient for a psychiatric consult. Following is a brief literature review of the matter.

Visual loss has been associated with affective disorders such as lower morale, depression, and diminished emotional security.¹⁶ One study found that patients with visual impairment had a 2.3 times greater risk of depression than those without a visual problem.¹⁷

A separate study looked at the effect of 11 common chronic conditions on depressive symptoms among African Americans.¹⁸ The investigators found that visual loss was one of only three conditions — along with renal and circulatory disorders — that independently predicted depression. Not surprisingly, researchers elsewhere determined that the primary link between chronic illness and depression has to do with functional disability.¹⁹

The stigma long associated with depression and other mental disorders has largely, if not entirely, dissipated. Thus retinal physicians need not be reluctant to address the matter in the face of evident signs and symptoms. Since the FDA approval of fluoxetine in December 1987 and later other selective serotonin reuptake inhibitors, as well as the advent of medications that work on the do pa mine and norepinephrine channels, patients have an array of generally effective antidepressant treatment options. Psychotherapy (talk therapy) is also held to be widely, if not universally, effective for many depressed patients.

TAKE-AWAY MESSAGES

Retinal physicians wishing to stay abreast of innovative medical treatments for intractable or otherwise baffling retinal disorders are well advised not to rule out off-label use of psychiatric or neurologic medications, as illustrated here.

In the meantime, you may be in position to do a tremendous favor for visually impaired patients with concomitant psychological disturbance by initiating an appropriate referral. RP

REFERENCES

1. Chen CC, Liu HC. Low-dose aripiprazole resolved complex hallucinations in the left visual field after right occipital lobe infarction (Charles Bonnet syndrome). Psychogeriatrics. 2011; 11:116-118.
2. American Foundation for the Blind. Charles Bonnet syndrome: Why am I having these visual hallucinations? Available at: http://www.visionaware.org/charles_bonnet_syndrome_why_am_i_having_these_visual_hallucinations. Accessed February 24, 2012.
3. Kazui N, Ishii R, Yoshida T, et al. Neuroimaging studies in patients with Charles Bonnet syndrome. Psychogeriatrics. 2009; 9:77-84.
4. Kester E. Charles Bonnet syndrome: case presentation and literature review. Optometry. 2009; 80:360-366.
5. Tan C, Sabel B. Dynamic changes in visual acuity as the pathophysiologic mechanism in Charles Bonnet sydrome (visual hallucinations). Eur Arch Psychiatry Clin Neurosci. 2006; 256:62-63.
6. Jackson M, Ferencz J. Cases: Charlles Bonnet syndrome: visual loss and hallucinations. CMAJ. 2009; 181:175-6.
7. Pae C, Serretti A, Patkar A, Masand P. Aripiprazole in the treatment of depressive and anxiety disorders: a review of current evidence. CNS Drug. 2008; 22:367-388.
8. Teunisse R, Cruysberg J, Hoefnagels W, et al. Social and pyschological characteristics of elderly visually handicapped patients with the Charles Bonnet syndrome. Compr Psychiatry. 1999; 40:315-319.
9. Clemson CM, Tzekov R, Krebs M, Checchi JM, et al. Therapeutic potential of valproic acid for retinitis pigmentosa. Br J Ophthalmol. 2011; 95:89-93.
10. Chapman A, Keane PE, Meldrum BS, et al. Mechanism of action of valproate. Prog Neurobiol. 1982; 19:315-359.
11. Macdonald RL, Bergey GK. Valproic acid augments GABA-mediated postsynaptic inhibition in cultured mammalian neurons. Brain Res. 1979; 170:558-562.
12. Berson EL, Rosner B, Sandberg MA, et al. A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol 1993; 111:761-72.
13. Berson EL, Rosner B, Sandberg MA, et al. Vitamin A supplementation for retinitis pigmentosa. Arch Ophthalmol. 1993; 111:1456-9.
14. Li T, Sandberg MA, Pawlyk BS, et al. Effect of vitamin A supplementation on rhodopsin mutants threonine-17 —> methionine and proline-347 —> serine in transgenic mice and in cell cultures. Proc Natl Acad Sci U S A. 1998; 95:11933-11939.
15. Vingolo EM, Rocco M, Grenga P, et al. Slowing the degenerative process, long lasting effect of hyperbaric oxygen therapy in retinitis pigmentosa. Graefes Arch Clin Exp Ophthalmol. 2008; 246:93-98.
16. Branch LG, Horowitz A, Carr C. The implications for everyday life of incident self-reported visual decline among people over age 65 living in the community. Gerontologist. 1989; 29:359-365.
17. Caraballese C, Appollonio I, Rozzini R, et al. Sensory impairment and quality of life in a community elderly population. J Am Geriatric Soc 1993; 41:401-407.
18. Bazargan M, Hamm-Baugh VP. The relationship between chronic illness and depression in a community of urban black elderly persons. J Gerontol B Psychol Sci Soc Sci. 1995; 50:S119-S127.
19. Verbugge LM, Patrick DL. Seven chronic conditions: their impact on U.S. adults' activity levels and use of medical services. Am J Public Health 1995; 85:173-182.
20. AMD Alliance International. Vision loss and depression. Available at: http://www.amdalliance.org/living-with-AMD-depression-overview.htm. Accessed February 24, 2012.