5. Quinolines
Antimalarial agents now used in the treatment of
autoimmune diseases, (RA) and (SLE).
Both medications have been shown to bind melanin and to
concentrate in the iris, ciliary body and retinal pigment
epithelium, altering normal physiologic function.
Early: asymptomatic, with only blunting of the foveal
reflex and RPE granular pigmentary changes.
With progression, symptoms can include blurred vision,
scotomas and photopsias.
Bilateral bulls-eye maculopathy .
6.
In late-stage disease, optic disc pallor.
Retinal toxicity has been shown in patients taking
greater than 3 mg/kg/day of chloroquine or 6.5
mg/kg/day of hydroxychloroquine.
Patients should be monitored annually, as toxicity can be
irreversible and even progress after drug cessation.
8. Thioridazine
Thioridazine (Mellaril) is a piperadine antipsychotic agent
Ocular toxicity was first described in 1980 and has been shown
in both short- and long-term treatment.
Bind to melanin in RPE and alter retinal enzyme kinetics
loss of photoreceptor ,RPE and CC.
Symptoms of toxicity include decreased vision and
dyschromatopsia.
Macular pigmentary changes can develop into a "salt-andpepper" pattern.
Long-term use can cause significant optic nerve atrophy and
destruction of both the RPE and choriocapillaris.
10. Chlorpromazine
Similar to thioridazine
Binds to melanin and can cause hyperpigentation of skin ,
conjunctiva, cornea, lens and retina.
Dose : 40-75 mg/day
2400 mg/day for 12 months: pigmentary changes, retinal
vessel attenuation, optic nerve pallor.
12. Deferoxamine
Deferoxamine is an iron-chelating agent used to treat
conditions with excessive serum iron levels, including
hemochromatosis.
1g IM initially and then 500mg Q4hr for 2 doses Maximum
dose: 6g in 24 hours
MO toxicity : due to removal of cu from RPE( crucial for the
normal functioning of antioxidant enzymes)
Vision loss, scotomas, dyschromatopsia, and nyctalopia.
RPE mottling may develop over time.
May cause diminished ERG amplitudes and late-phase
vascular leakage on FA.
Deferoxamine toxicity is reversible with drug cessation,
with full recovery of visual function.
13.
14. Clofazimine
Red phenazine dye antimycobacterial agent
Capsule 50 mg, 100 mg
Used for leprosy, psoriasis, pyoderma
gangrenosum, DLE , mycobact.avium complex
infection in HIV pt.
50 mg daily for at least 2 years
Clofazimine crystal deposition in cornea.
Bulls eye maculopathy.
Retinopathy with 200-300 mg/day and
irreversible.
15. Cisplatin
Used in Malignant glioma ,metastatic breast cancer, testicular
cancer.
1st change: Pigmentary retinopathy in macula with abnomal
ERG
2nd : CWS, hemorrhages , macular exudates , optic
neuropathy with disc swelling.
3rd : Arterial occlusion , vasculitis , papilitis
MO toxicity: Due to platinum toxicity to retina
Begins 6 weeks after drug initiation.
Others : pain, chemosis,secondary glaucoma, internal
ophthalmoplegia,cavernos sinus syndrome.
Progressive ..no treatment.
16. Quinine sulphate
Treatment for Nocturnal muscle cramps or restless leg
syndrome
Recommended dose : less than 2 g/day.
Toxicity wt >4 g and fatal dose is 8 gm.
Mechanism of toxicity is not known: disruption of
cholinergic transmission and it is vascular in origin.
Cinchonism ( syndrome due to overdose): nausea, vomiting
,headache, tremor, LOC, blindness.
Fundus : venous dilatation with retinal oedema
VA returns with field defect and optic disc pallor after few
weeks to months.
18. Talc
Talc, an inert filler used in oral powdered medications.
Talc retinopathy inevitably indicates a history of intravenous
drug abuse.
The talc deposits range from 5 to 10 µm.
Refractile yellow opacities in the macula.
Lodge in the macular arterial vasculature, causing a
granulomatous reaction with focal occlusion, leading to
eventual macular ischemia.
Ischemic sequelae include peripheral retinal or optic disk
neovascularization, vitreous hemorrhage and arteriovenous
anastomosis.
FA imaging will show capillary nonperfusion, enlargement of
the foveal avascular zone and vascular leakage.
21. Oral contraceptive
The synthetic estrogen and progesteron effect
coagulation factors
hypercoagulable state
theomembolic complicaton.eg CRVO, CRAO.
22. Aminoglycoside
Gentamicin, tobramycin, amiikacin
Massive doses :retinal hemorrhages,retinal
oedema,CWS, arteriolar narrowing, venous
beading.
Rubiosis iridis, NVG,pigmentary retinopathy, optic
atrophy.
FFA: severe vascular nonperfusion in acute stage
Preservative ( methylparaben,
propylparaben,edetate disodium) play an additive
role in its toxicity.
23.
Retinal toxicity enhanced by :
a) Intravitreal injection bevel end pointing towards retina
b) Increased rate of injection
100 -400 ug can still produce toxicity
Gentamicin small doses cause formation of abnormal
lamellar lysosomal inclusions in the RPE.
large doses cause retinal necrosis.
Pt should be placed upright as soon as possible after surgery
as gravity produces toxicity to the macula.
25. Interferon
Interferon (Betaseron) is a recombinant DNA-based protein
used in the treatment of hepatitis C, leukemia, lymphoma
and multiple sclerosis.
Toxicity is due to deposition of immune complex, activated
complement C5a wt leukocyte infiltration.
Retinopathy : Cotton-wool spots, intraretinal and pre-retinal
hemorrhage, and macular edema.
Signs develop within two weeks to three months of
treatment onset.
High risk for diabetic and/or hypertensive patirnts.
Disc oedema, CRVO, BRVO, AION, CME.
Resolve spontaneously when discontinued,
28. Epinephrine
Sympathomimetic agent
It acts to lower IOP by decreasing aqueous production
Patients complain of blurred or decreased vision within
weeks to months of initiating therapy.
Topical epinephrine may produce cystoid changes by
reducing blood flow in the retina and choroid.
Two points : one is the stimulation of PG synthesis ,the
other is the dysfunction, in some aphakic eyes, of the
active transport system which is responsible for the
removal of PGs from intraocular fluids
CME will resolve with drug cessation.
29. Latanoprost (Xalatan)
Latanoprost (Xalatan) is a prostaglandin analog
used to lower IOP by increasing uveoscleral
outflow.
Should not exceed once daily.
Toxicity occures if used > 6 months.
Conjunctival hyperemia, darkening of eyelashes
and iris heterochromia ,reversible cystoid macular
edema
As a PG analog, latanaprost is thought to
contribute to the disruption of the blood–aqueous
barrier and angiographic CME formation in early
postoperative pseudophakes.
The CME is reversible on discontinuation of the
latanoprost
32. Niacin
Niacin, or vitamin B3, is used to treat pellagra,
hyperlipidemia and hypercholesterolemia.
Initial dose: 100 mg orally 3 times a day,.
Maintenance dose: 1 to 2 g orally 3 times a day
The maximum recommended dose is 6 g/day.
Niacin has direct toxic effects on Müller cells, without
disruption of the blood-retinal-barrier.
Systemic side effect: facial flushing
Visual complaints: blurred vision/decreased vision and
metamorphopsia.
33.
Macula appears edematous
FA is silent without leakage, which is thought to
indicate that the edema is secondary to fluid
accumulation inside retinal cells, as opposed to an
extracellular location.
While OCT imaging exhibits classic cystic space in
the inner nuclear and outer plexiform layers.
The discontinuation of niacin will gradually reduce
CME and improve visual acuity.
34. Pactitaxel /docetaxel
Antineoplastic agent /antimicrotubule agent
Treats different kinds of cancer, including cancer
in the lungs, ovary, or breast.
Also may be used to treat Kaposi's sarcoma.
Angiographically negative CME.
Toxic dose:135mg/m2 infusion every 3 wks
36. Tamoxifen
Tamoxifen is a selective estrogen receptor modulator
used in the management of breast cancer.
It is an amphiphilic agent that can accumulate in
lysosomes and cause oxidative damage.
The mechanism of ocular toxicity : has been postulated
that the cationic amphiphilic nature of tamoxifen allows
binding with polar lipids, interfering with their
catabolism.
Patients may be asymptomatic at onset but may
complain of decreased vision and dyschromatopsia.
Ocular symptoms: doses greater than 60-100 mg/day
over 1 year.
Clinically, fundus examination will show refractile
intraretinal crystalline deposits concentrated primarily
in the perifoveal macula,Optic neuropathy,CME.
38. Canthaxanthine
Canthaxanthine is a vitamin A derivative used in the
treatment of psoriasis, eczema, vitiligo.
Toxicity has been shown after high-dose oral therapy
of greater than 0.5 mg/kg/day over 2 years.
Patients are primarily asymptomatic
On fundus exam, a doughnut-shaped ring of golden
intraretinal deposits surrounds the fovea.
FA, ERG and color vision are typically normal;
however OCT demonstrates crystalline deposition
within the inner retinal layers.
Visual field testing shows a dose-dependent decrease
in retinal sensitivity
39.
Patients should be monitored with regular
ophthalmologic examination.
With drug cessation, the retinal crystals may take
years to disappear, while patients often remain
asymptomatic.
Canthaxanthine crystals are localised in the
degeneration neutrophil and associated with atrophy
of muller cells.
Vacuolization of RPE and disruption of
phagolysosome.
41. Methoxyflurane
Inhalational anaesthetic agente
Specially used in patients with renal insufficiency,
Biodegradation product inorganic flouride and
dichloroacetic acid is responsible for the toxicity.
Metabolized to oxalic acid
combine with Ca
Ca oxalate salt
deposited in RPE
Each 3 milliliter dose lasts approximately
30 minutes
Pain relief begins after 6–8 breaths and continues
for several minutes after stopping inhalation.
The maximum recommended dose is 6 milliliters
per day or 15 milliliters per week.
Yellow white punctate lesion in posterior pole and
periarterially.
44.
Cause a syndrome of transient
acute myopia and anterior chamber
shallowing.
This is due to ciliary body swelling,
choroidal effusion or lens swelling
with forward rotation of lens iris
diaphragm.
Folds develop due to vitreous
traction on the macula that is
caused by forward shift of the lens
and iris.
Chlorthalidone-induced retinal folds
45. Miscellaneous Medications
Sildenafil: Sildenafil (Viagra) is a selective inhibitor of
cGMP-specific phosphodiesterase type 5 (PDE5) that causes
smooth muscle relaxation.
Sildenafil also acts on the retina to alter cGMP levels by
inhibiting retina-specific PDE6
depolarization of the
rod cell & influences the phototransduction cascade and
increased light sensitivity.
Patients may present with visual disturbances, complaining
of cyanopsia, photophobia and blurred vision.
Typically, visual acuity is unchanged and there are no fundus
changes.
Case reports have also described NAAION, CSR, cilioretinal
arterial occlusion et.
Symptoms resolve over four to six hours after medication
ingestion.
46. Digoxin
Digoxin (Lanoxin) is a cardiac glycoside: used in
atrial fibrillation, atrial flutter and congestive
heart failure.
Systemic toxicity is rare when plasma digoxin
concentration is less than 0.8 µg/L.
Ocular side effects are common with high doses,
Decreased vision to photopsias, xanthopsia and
scotomas.
Digoxin acts on retinal cells by inhibiting the
sodium-potassium ATPase pump and altering
potassium levels.
When digoxin is stopped, both the visual symptoms
and prolonged ERG b-wave will resolve over weeks
as the medication is metabolized
47. Methanol
Visual blurring and field defect within 18 hrs.
Toxicity is mediated by formic acid which affects
the inner retina and optic nerve.
Vision loss is thought to be caused by interruption
of mitochondrial function in the optic nerve.
Optic nerve demyelination has been reported to
be due to formic acid destruction of myelin
resulting in hyperemia, edema, and optic nerve
atrophy.
48. Carbamazepine
Carbamazepine is an anticonvulsant
200 mg orally twice a day.
Maintenance dose: 800 to 1200 mg/day
Dosage generally should not exceed 1200 mg/day
Might cause damage of the retinal pigment epithelium in
long-term treatment.
Fundus : Extensive lesions of the retinal pigment epithelium
in the posterior poles of the eyes including the macular
regions.
Discontinuation of carbamazepine lead to improvement of
visual function.
49. Conclusion
The exact mechanisms of pathogenesis for many
of these drugs remain unknown.
Early detection and prompt treatment are often
crucial in reversing these adverse ocular effects.
The associated clinical presentations, colour
vision, contrast sensitivity, FFA, OCT, perimetry ,
Electrophysiological tests are important aids for
diagnosis.
