ADDICTION AND VISION ADDICTION AND VISION LOSSLOSS

Bruce Kastner, M.S., O.D.,Bruce Kastner, M.S., O.D.,

Clinical Coordinator, Clinical Coordinator,

CBVICBVI

ACKNOWLEDGMENTSACKNOWLEDGMENTS

Spalton, Atlas of Clinical Ophthalmology, 3Spalton, Atlas of Clinical Ophthalmology, 3rdrd Edition, Edition, 20052005Onofrey, Ocular Therapeutics Handbook, 2Onofrey, Ocular Therapeutics Handbook, 2ndnd Edition, Edition, 20052005Kunimoto, Danitkar, and Makar, The Wills Eye Manual, Kunimoto, Danitkar, and Makar, The Wills Eye Manual, 44thth Edition, 2004 Edition, 2004EyeRounds.orgEyeRounds.orghttp://www.opt.indiana.edu/ce/syspharm/part2.htm http://www.kellogg.umich.edu/theeyeshaveit/side-effects/chloroquine.htmlSteel, JR, Cockcroft, JR an Ritter, JM, “Blind drunk: Steel, JR, Cockcroft, JR an Ritter, JM, “Blind drunk: alcoholic pancreatitis and loss of vision.” alcoholic pancreatitis and loss of vision.” Postgrad Med J Postgrad Med J (1993) 69, 151-152.(1993) 69, 151-152.

OCULAR STRUCTURESOCULAR STRUCTURES

Cornea – clear, anterior-mostCornea – clear, anterior-most

Iris – Colored, contains pupilIris – Colored, contains pupil

Anterior chamber – between cornea and lensAnterior chamber – between cornea and lens

Lens – focuses light onto retinaLens – focuses light onto retina

Posterior chamber – between lens and retinaPosterior chamber – between lens and retina

Retina – photoreceptors; converge to form optic Retina – photoreceptors; converge to form optic nervenerve

Optic Nerve – sends signal to brain for Optic Nerve – sends signal to brain for perceptionperception

OCULAR STRUCTURESOCULAR STRUCTURES

Retina – 10 layers Retina – 10 layers – Macula – most sensitive part of retina – Macula – most sensitive part of retina –

Responsible for best resolution (20/20, color vision Responsible for best resolution (20/20, color vision and central vision)and central vision)

– PhotoreceptorsPhotoreceptorsRods = peripheral vision, black and white, 20/400Rods = peripheral vision, black and white, 20/400

Cones = central vision, color, 20/20Cones = central vision, color, 20/20

NORMAL RETINANORMAL RETINA

RETINAL STRUCTURESRETINAL STRUCTURES

VISION LOSS DUE TO TOXICITYVISION LOSS DUE TO TOXICITY

Toxic optic neuropathy – differential Toxic optic neuropathy – differential diagnosisdiagnosis– Tobacco/alcohol abuseTobacco/alcohol abuse– Severe malnutrition (thiamine deficiency) – Severe malnutrition (thiamine deficiency) –

Vitamin B1 deficiencyVitamin B1 deficiency– Pernicious anemia (problem with B12 Pernicious anemia (problem with B12

absorption)absorption)– Toxic (cloramphenicol, ethambutol, isoniazid, Toxic (cloramphenicol, ethambutol, isoniazid,

digitalis, chloroquine, streptomycin, lead, etc)digitalis, chloroquine, streptomycin, lead, etc)

TESTING FOR TOXICITYTESTING FOR TOXICITY

CBC (rule out macrocytic anemia CBC (rule out macrocytic anemia associated with alcoholism)associated with alcoholism)

Serum vitamin B12 Serum vitamin B12

Serum folateSerum folate

Screening for metal toxicity (lead)Screening for metal toxicity (lead)

OPTIC NEUROPATHYOPTIC NEUROPATHY

Damage to the optic nerve due to any causeDamage to the optic nerve due to any causeMost recognized cause: methanol intoxication.Most recognized cause: methanol intoxication.– Victim usually mistakes or substitutes methanol for ethyl alcohol.Victim usually mistakes or substitutes methanol for ethyl alcohol.– Blindness occurs with drinking as little as one ounceBlindness occurs with drinking as little as one ounce– Initial nausea and vomiting followed by respiratory distress, Initial nausea and vomiting followed by respiratory distress,

headache and vision loss starting 12 hours after consumptionheadache and vision loss starting 12 hours after consumption– Ethylene glycol (component of antifreeze) is toxic to the entire Ethylene glycol (component of antifreeze) is toxic to the entire

body causing permanent neurological and ophthalmic lossbody causing permanent neurological and ophthalmic lossIncreased intracranial pressure causes swelling of the optic Increased intracranial pressure causes swelling of the optic nerve and cerebral edemanerve and cerebral edemaTREATMENT FOR METHANOL AND ANTIFREEZE TREATMENT FOR METHANOL AND ANTIFREEZE TOXICITY IS ETHANOL CONSUMPTIONTOXICITY IS ETHANOL CONSUMPTION

METHANOL TOXICITYMETHANOL TOXICITY

Edema secondary to increased pressureEdema secondary to increased pressure

METHANOL TOXICITYMETHANOL TOXICITY

MRI on day 15 after methanol intoxication. (a) T2-MRI on day 15 after methanol intoxication. (a) T2-weighted image showed high signal abnormalities in weighted image showed high signal abnormalities in bilateral basal ganglia (arrows), frontal, and occipital bilateral basal ganglia (arrows), frontal, and occipital subcortical white matter (arrowheads), consistent with subcortical white matter (arrowheads), consistent with oedematous changeoedematous change. (b) T2-weighted image showed . (b) T2-weighted image showed oedematousoedematous change involving bilateral optic tracts and change involving bilateral optic tracts and optic radiations (arrows). High signal optic radiations (arrows). High signal oedematousoedematous change was also noted in the optic disc of left eye change was also noted in the optic disc of left eye (arrowheads). (c) T1-weighted image showed slightly (arrowheads). (c) T1-weighted image showed slightly high signal component in bilateral basal ganglia, high signal component in bilateral basal ganglia, indicating the indicating the haemorrhagehaemorrhage (arrows). (d) T1-weighted (arrows). (d) T1-weighted image with gadolinium administration showed marginal image with gadolinium administration showed marginal enhancement in bilateral putamen, indicating enhancement in bilateral putamen, indicating breakdown breakdown of the blood−brain barrierof the blood−brain barrier..

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

Methanol is metabolized in the liver and Methanol is metabolized in the liver and converted to formic acid (toxic) resulting in converted to formic acid (toxic) resulting in systemic systemic metabolic acidosismetabolic acidosisOnset of vision loss and central nervous system Onset of vision loss and central nervous system effects are delayed for 12-24 hours, effects are delayed for 12-24 hours, corresponding to the time for methanol to be corresponding to the time for methanol to be converted to its toxic metabolitesconverted to its toxic metabolitesLaboratory testing can take one day to complete, Laboratory testing can take one day to complete, so toxicity is not usually diagnosed in the ERso toxicity is not usually diagnosed in the ERBest treatment: gastric lavage, treatment of the Best treatment: gastric lavage, treatment of the metabolic acidosis and competitive inhibition of metabolic acidosis and competitive inhibition of methanol oxidation by ethanol or methypyrazolemethanol oxidation by ethanol or methypyrazole

PATHOPHYSIOLOGY – CASE STUDYPATHOPHYSIOLOGY – CASE STUDY

Alcoholic pancreatitis with deliriumAlcoholic pancreatitis with delirium– Treatment with parenteral vitaminsTreatment with parenteral vitamins– Sedated with intravenous chlormethiazoleSedated with intravenous chlormethiazole– Rehydrated with physiological salineRehydrated with physiological saline– BP 140/80BP 140/80

– Next day: delirium resolvedNext day: delirium resolved– Normal temperatureNormal temperature– BP stabileBP stabile– Oriented and rationalOriented and rational– ““completely blind”completely blind”

PATHOPHYSIOLOGY – CASE STUDYPATHOPHYSIOLOGY – CASE STUDY

Reason for original visit – “blurred vision”Reason for original visit – “blurred vision”– Denied drinking methylated spiritsDenied drinking methylated spirits– Normal pupillary reflexNormal pupillary reflex– Ophthalmoscopy revealed cotton wool spots (infarcts Ophthalmoscopy revealed cotton wool spots (infarcts

– similar to that associated with hypertension) with a – similar to that associated with hypertension) with a cherry red spot in the macula OD (evidence of toxicity cherry red spot in the macula OD (evidence of toxicity and loss of macular function)and loss of macular function)

– Admitted to abusing drugs up to 2 years previously Admitted to abusing drugs up to 2 years previously and shared needles and shared needles

– Blood work: (-) HIV; (-) lupus erythematosusBlood work: (-) HIV; (-) lupus erythematosus– Ultrasound of abdomen: Ultrasound of abdomen: enlarged pancreasenlarged pancreas

PATHOPHYSIOLOGY – CASE STUDYPATHOPHYSIOLOGY – CASE STUDY

Minimal improvement in vision one month Minimal improvement in vision one month after diagnosisafter diagnosisEtiology of pancreatic retinopathy Etiology of pancreatic retinopathy uncertain: granulocyte aggregates uncertain: granulocyte aggregates (activated by the complement system) (activated by the complement system) versus fat emboli result in vascular versus fat emboli result in vascular occlusionsocclusionsRetinal treatment is conservative – limited Retinal treatment is conservative – limited to observation and supportive careto observation and supportive care

MACULAR TESTINGMACULAR TESTING

Color testing – Color testing – Ishihara platesIshihara plates

Automated visual Automated visual fieldsfields

ADDITIONAL TESTINGADDITIONAL TESTING

TESTS TO DETERMINE TYPE OF TESTS TO DETERMINE TYPE OF TOXICITYTOXICITY

Color visionColor visionElectrodiagnostic testingElectrodiagnostic testing– ERG – electroretinogram (tests layers of ERG – electroretinogram (tests layers of

retina)retina)– VEP – tests entire visual pathway to occipital VEP – tests entire visual pathway to occipital

lobelobe

Visual fieldVisual field– Amsler (specific for macula – central)Amsler (specific for macula – central)– Automated fieldAutomated field

DRUG TOXICITYDRUG TOXICITY

44 y/o female with acute onset of paracentral scotomas (visual 44 y/o female with acute onset of paracentral scotomas (visual field loss around the central field) in right eye (corresponded field loss around the central field) in right eye (corresponded directly to Amsler grid findings) – What should be tested?directly to Amsler grid findings) – What should be tested?

TAMOXIFEN MACULOPATHY Tamoxifen (Nolvadex, Emblon, Noltam, Tamofen) is an anti-estrogen used to treat breast carcinoma. It has few systemic side-effects at a traditional normal dose of 20 to 40mg/day. Current dosages prescribed today may be even less, reducing the prevalence of side-effects. Vortex keratopathy and optic neuritis can rarely occur, which usually is reversible on cessation of therapy. Retinotoxicity presents as multiple superficial yellow crystalline ring-like deposits at the macula, that can cause visual acuity loss (Figure 29).

(Source: http://www.opt.indiana.edu/ce/syspharm/part2.htm http://www.opt.indiana.edu/ce/syspharm/part2.htm)

ANTIMALARIAL TOXICITY

Chloroquine (Nivaquine, Avlocor) and Hydroxychloroquine (Plaquenil) are used in treating malaria and rheumatological disorders (i.e. rheumatoid arthritis, lupus). Excess of 300g cumulative oral dose(250mg/day for 3 years) significantly increases risk of maculopathy. Hydroxychloroquine has less maculopathy risk than chloroquine, and as such is typically the preferred medication to prescribe (Figure 26).

Source: http://www.kellogg.umich.edu/theeyeshaveit/side-effects/chloroquine.html)

TALC RETINOPATHYTALC RETINOPATHY

TALC RETINOPATHYTALC RETINOPATHY

CONCLUSIONSCONCLUSIONS

IV drug users are susceptible to emboli which IV drug users are susceptible to emboli which deprive retinal structures of oxygen secondary to deprive retinal structures of oxygen secondary to talc which is added to “cut” the drug. Cortical talc which is added to “cut” the drug. Cortical damage can also occur, but the emboli tend to damage can also occur, but the emboli tend to travel downstream to the smaller vessels where travel downstream to the smaller vessels where they lodgethey lodgeAlcohol abuse results in death of retinal Alcohol abuse results in death of retinal structures – structures – – Loss may be sudden and irreversible if methanol is Loss may be sudden and irreversible if methanol is

ingestedingested– Loss may be gradual, permanent with sustained Loss may be gradual, permanent with sustained

nutritional amblyopia secondary to ethanol abuse. nutritional amblyopia secondary to ethanol abuse. This is generally caused by lack of vitaminsThis is generally caused by lack of vitamins