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ERA’S JOURNAL OF MEDICAL RESEARCH VOL.6 NO.1 Review Article

OCULAR SIDE EFFECTS OF SYSTEMIC DRUGS

Pragati Garg, Swati Yadav Department of Era's Lucknow Medical College & Hospital, Sarfarazganj Lucknow, U.P., India-226003

Received on : 06-03-2019 Accepted on : 28-06-2019 ABSTRACT Systemic drugs are frequently administered in persons of all age group Address for correspondence ranging from children to the elderly for various disorders. There has been Dr. Pragati Garg increased reporting of ocular side effects of various systemic drugs in the Department of Ophthalmology past two decades. Some offenders well known are α -2-adrenergic agonists, Era’s Lucknow Medical College & quinine derivatives, β- adrenergic antagonists and antituberculosis drugs. Hospital, Lucknow-226003 Newer systemic drugs causing ocular side effects are being reported in Email: [email protected] available literature. Knowledge regarding these is expected to aid Contact no: +91-9415396506 clinicians in identifying these side effects and the offending drug, thereby, prescribing the appropriate treatment for the condition the patient maybe suffering from without any ocular disturbances. KEYWORDS: Ocular side effects, Systemic drugs. Introduction This article will briefly cover how systemic drugs can Many common systemic medications can affect ocular affect the various ocular structures. tissues and visual function to varying degrees. When a Factors Affecting The Production Of Ocular Side systemic medication is taken to treat another part of the Effects By A Drug body, the eyes frequently are affected. Systemic A) Drug related factors medications can have adverse effects on the eyes that range from , and to (1) The nature of the drug: Absorption of drug in blinding complications of toxic and optic body and its pharmacological effects on the body's neuropathy (1). Some of these side-effects, though metabolism is effected by nature of drug. The ease undesirable, have to be accepted as unavoidable. The with which a drug passes into the general circulation discovery of serious ocular defects arising in and into the eye determines the ability of systemically association with the long-term use in high dosage of administered drugs to affect the eye directly. certain drugs has indicated the need for all prescribers (2) The amount of the drug consumed: The daily to be aware of the risks involved. Particularly this is consumption of high doses of drugs reaches toxic important since some of the toxic effects have seriously levels to effect the eye. In addition, prolonged impaired vision and proved to be irreversible. consumption of drugs whose detoxification and When patients present with ocular symptoms that have excretion is low determines the effect on eyes. no apparent cause, it is important to consider whether (3) The route of its administration:Drugs the condition could be caused by a systemic areadministered locally, orally or through parenteral medication they are taking. Patients often neglect to route. Topical application of drugs, allows sufficient mention the maintenance drugs that they take every absorption to risk ocular side effects. day, so ophthalmologists may need to ask specifically (4) Pathological condition of patient: Liver and about theseEJMR types of medication. One of the most renal diseases frequently affect the detoxication and important aspect is obtaining a thorough medical excretion of drugs, allowing them to accumulate to history which includes specific medication dosage and toxic levels. In some instances, it is difficult to duration of treatment (2). Patient safety is essential determine whether an ocular defect has arisen as a during treatment for a particular disorder. result of involvement with the general disease or as a There is much awareness of systemic effects of ocular toxic manifestation of a drug used in therapy. eye drops due to absorption through nasal mucosa. It is (5) Effect of drug combination: Certain drugs much needed to be aware of the ocular side effects of consumed in combination with other substances have systemic drugs also for better patient compliance and potentiated toxic effects. satisfaction . ERA’S JOURNAL OF MEDICAL RESEARCH, VOL.6 NO.1 Page: 1 OCULAR SIDE EFFECTS OF SYSTEMIC DRUGS

(6) Previous exposure to the drug: The ability of the non pigmentedciliary epithelium, which causes non-protein drugs to act as haptens sensitize the reduction in aqueous formation by the (5). patient and are thus, responsible for iatrogenic disease, Topical β2 blockers produce little additional IOP particularly where drugs are applied topically over reduction with concomitant administration of a non- long periods. selective (β1 and β2) systemic beta-blocker. Some (7) Drug metabolism: The body's ability to patients may be misdiagnosed as normal tension metabolize a drug directly correlates with toxicity. In because the IOP is artificially reduced, patients with liver and kidney disease, there is a appearing within normal limits. decreased rate of excretion, which allows drug 2. Diuretics molecules to accumulate to toxic levels (3). Also, toxic Hydrochlorothiazide (HCTZ) is a diuretic metabolites formed elsewhere like the liver, can reach commonly used to treat congestive heart failure, and the eye through systemic circulation or can be sometimes causes dry eye by changing the tear film. It produced locally in ocular tissues. reduces lysozyme levels and immunoglobulin A, and B) Ocular factors also causes a decrease in aqueous production and. The The eyes are generally affected when a systemic tear potassium is found decreased significantly in medication is taken to treat some other part of the body. subjects taking hydrochlorothiazide (6). Myopic shift Following systemic administration, the and band keratopathyhave been reported, however, blood–aqueous barrier and blood–retinal barrier are occurrence is not common (6). Exact mechanism the major barriers for anterior segment and posterior producing acute is not very clear even though segment ocular drug delivery, respectively4. The it has been postulated to be due to ciliary body effusion, (7) peripheral uveal effusion (8) and ciliary , and ciliary body have thin, fenestrated 9 walls for drug molecules to pass through. Small, lipid spasm and swelling. Oral sulphonamides cause soluble molecules, which pass freely into the aqueous transient myopia as a result of forward displacement of humor,can further diffuse into a circulation .The drug the lens due to allergic ciliary body oedema and molecules can enter the eye and contact various ocular rotation (9-10). tissues, and eventually accumulate in ocular tissues or 3. Angiotensin Converting Enzyme (ACE) exit the eye. There are three major accumulation sites Inhibitors including the , lens and vitreous. The duration These are commonly used as antihypertensive drugs of action of drug in the eye is prolonged if it is which can cause decreased vision, photosensitivity, deposited, increasing chances for toxicity (4). , lid edema and discoloration and The cornea has a permeable endothelium, and . Enzyme activities of ACE have been thestomaglycosaminoglycans (GAGs) which can reported further in production of aqueous humour, bindto drug molecules, leading to edema and vitreous humour and tear fluid, also in , and decreased transparency. Drug molecules can also bind ciliary body, which are inhibited by these drugs (11). to lens proteins and photosensitize the lens to 4. Antiarrhythmics ultraviolet (UV) radiation. Lastly, drug molecules tend to accumulate in the vitreous due to the slow rate of a) Amiodarone: It is used to treat various cardiac fluid exchange in the lens, cornea, and trabecular arrhythmias like atrial fibrillation and meshwork (2). ventriculartachycardia, which causes certain ocular side effects. Studies have found the presence of List Of Ocular Side Effects Of Some Common amiodarone in all ocular tissues when systematically Systemic Drugs administered. Keratopathy is the mostcommon ocular A) Antihypertensive drugs adverse effect of amiodarone found in almost all 1. Beta-blockers: Beta- blockers,used to treat patients (70-100%) (12). It most commonly appears EJMRafter 1-4 months of therapy. Involvement is bilateral hypertension, reduce tear lysozyme levels and immunoglobulin A(IgA) which leads to reduction in but is often asymmetric. Toxicityincreases with higher tear secretion, and patients complain of ocular doses and longer therapy. irritation, dry eye symptoms, and contact lens Amiodarone tends to cause whorl-like corneal intolerance (5). deposits in as early as six days of treatment butmore Artificial tear supplementation and refitting the patient commonly in one to three months of treatment. The with softcontact lenses should be done as deposits appear whorl-like because epithelial cells management. Beta blockers also decrease intraocular migrate centripetally from limbus. pressure (IOP) by blocking the beta-2 (β2) receptors on ERA’S JOURNAL OF MEDICAL RESEARCH, VOL.6 NO.1 Page: 2 Jan - Jun 2019 ERA’S JOURNAL OF MEDICAL RESEARCH VOL.6 NO.1

sodium, necessary for aqueous secretion. It inhibits the transport of Na+necessary for aqueous secretion and thus causes reduced aqueous secretion and IOP2. Along with the ocular side effects, there are numerous systemic side effects associated with this drug precluding its use in a b c glaucoma treatments (15). Other ocular side effects reported regularly with use of digoxin are blurred vision and peri-central (16). d e f g b) Anti-anginal drugs Fig 1:(a) Blue-grey Discoloration On The Nose And · Nitroglycerin: leads to decreased vision and Central Cheeks. Amiodarone - Induced Corneal coloured halos, variations in intraocular pressure, Opacities; (b) Horizontal Line In The Inferior Third pseudotumor cerebri, Ocular side effects observed Of The Cornea In The Right Eye, (c) Whorl-Like with other antianginal drug include photosensitivity, Pattern Of Powdery, White, Yellow Or Brown , periorbital edema, lacrimation, Corneal Deposits Of The Left Eye. In Vivo Confocal subconjunctival and retinal hemorrhages (15). Microscopic Images Of Hyperreflective Intracellular c) Antithyperlipidemics Inclusions Of Amiodarone Keratopathy (d) In Patients with high cholesterol are often treated with Epithelial Cells, (e) In Basal Epithelial Cells, (f) In anti-hyperlipidemicdrugs.One of the earlier Stroma, (g) No Deposits In The Endothelium (13). investigations of lovastatin showed high rate of lens Severity of keratopathy appears to significantly opacities (14) Statins inhibit lens epithelial cell death. correlate with total drug dosage and duration of therapy. This supports the theory that oxidative damage to the Patients taking higher doses >400mg/day demonstrate lens epithelium may cause proteins to coagulate and more advanced keratopathydepending on the duration form . Perhaps statins scavenge the free of treatment. Keratopathy remains relatively stationary radicals that damage the lens with light and until the drug dosage is reduced. Keratopathy resolves oxygen.Anti-hyperlipidemics lead to dry eye and within 3-20 months of discontinuation of the cystoid (11). Symptoms of lid edema medication. corneal changes associated with and blurred vision may also occur (2). amiodarone therapy are benign and special follow up of G) Hypoglycemic drugs affected patients is not needed (12). · Chlorpropamide is used less often with the advent of second generation sulphonylureas.However, certain ocular side effect are worthy of note. It can result in central or centrocaecalscotoma. This effect is acute and bilateral, but reduces if the drug is Grade 1 Grade 2 Grade 3 Grade 4 discontinued. Visual loss due tochlorpropamide- induced was also reported (17) Fig 2: Grades of Amiodarone Keratopathy · Sulphonylureas like glibenclamide and Being photosensitizing agent, amiodarone can also gliclazidehave been used to treat diabetes (3).These causes anterior and posterior sub-capsular lens have shown to inhibit the vasoconstriction of retinal changes. It also has tendency oflipid storage in cornea and ciliary arteries induced by prostaglandins. This and lens (2). There have been recent cases of optic may have the result of increasing blood flow in the neuropathy with vision loss as well as reports of diabetic retina as an extra beneficial effect. On the other Pseudotumorcerebri, however these were also hand, the protective effect on retina is blocked by observed toEJMR be reversible with the discontinuation of another sulphonylurea, tolbutamide (18). Some amiodarone therapy (14). glycation end products (AGEs) promote the expression of vascular endothelial growth. Gliclazide has been Reduction of IOP in glaucomatous and non- shown to inhibit this process. This action can be glaucomatouseyes is also reported (2). attributed to the antioxidant properties of this drug (19). a) Cardiac glycosides- Digitalis/digoxin Gliclazide in particular has also been shown very Digoxin has been known for a very long time to cause recently (20) to inhibit retinal leukostasis. (Early visual effects, photoreceptor color vision phenomena. leukocyte entrapment in the retinal microvasculature is Itinhibits Na+-K+ATPase in the ciliary epithelium (10). regarded as one of the pathogenetic mechanisms of This enzyme is responsible for the active transport of .)Lightman (21) reported in

ERA’S JOURNAL OF MEDICAL RESEARCH, VOL.6 NO.1 Page: 3 OCULAR SIDE EFFECTS OF SYSTEMIC DRUGS patients on glyburide, a second generation Lupron leads to ocular side effects of temporary sulphonylurea, development of crystalline lens blurred vision for several hours up to three weeks. This changes and shifts in the absence of is also known to cause pseudotumor cerebri and retinal variations in blood glucose level. This drug is a more vascular occlusions owing to its thromboembolic potent osmotic agent than its predecessors. property (2, 26). 3) Thiazolidinediones ( TZDs) - The more recently 5) Tamsulosin(Flomax)- The most critical ocular introduced but yet widely prescribed agents, side effect of this medication is known as pioglitazone and rosiglitazone, have been intraoperative Floppy syndrome (IFIS), which can demonstrated in animal models to inhibit the causecomplications to occur during cataract surgery p r o g r e s s i o n o f r e t i n a l a n d c h o r o i d a l (27). Although the precise mechanism by which neovascularization, both in diabetes mellitus and tamsulosin can lead to IFIS remains unknown, Chang . This is achieved via inhibition et al. (28) suggest that tamsulosin has a high affinity of vascular endothelial growth factor/VEGF induced and specificity for the α1A adrenergic receptor, which proliferation migration and tube formation of retinal is thought to be the dominant receptor in the iris It is endothelial cells(RECs) (22). Association of macular important for the patient to inform their eye surgeon edema with use of a TZD has been reported in some that they are on this medication prior to cataract case reports and review articles but the overall surgery, to allow the surgeon to take additional evidence either proving or disproving it is fair at best. measures during surgery including using iris hooks, However, most experts in the field believe that TZDs iris dilator rings or viscoelastic substances to help keep probably exacerbate macular edema and that with the iris from intra operative or iris prolapsing discontinuation of TZDs, macular edema may into the phacoemulsification incisions (2). decrease or abate completely (23). 6) Sildenafil (Viagra) - It is a potent drug for D) Hormones Erectile Dysfunction which can cause a bluish tinge to 1) Levothyroxine: Longterm use of Levothyroxine objects, blurred vision and hypersensitivity to light. have been found to lead to visual hallucinations, Thesesymptoms are reversible and last a few minutes hyperemia and pseudotumorcerebri (PTC), which to several hours. Few cases of anterior ischemic optic disappear with discontinuation of the drug (3). Some neuropathy and non-arteritic ischemic optic patients have noticed visual hallucinations with this neuropathy have been reported which can cause drug. Use of oral contraceptive is commonly known to permanent vision loss 2. This has been attributed to cause dry eye and contact lens intolerance from inhibition of PDE6 mediated photo-transduction reduced tear secretion (2). process (29). 2) Hormone Replacement Therapy (HRT) with E) Central nervous system (CNS) agents Estrogen-Ocular adverse reaction observed with this Central nervous system (CNS) agents are becoming drug include retinal vascular thrombosis, dry eye, the most commonly prescribed class of medication in migraines and pseudotumor cerebri (24).The exact the world.In general, may be cause has not been proven, but may be associated with inexplicably reduced, color vision altered, pigmented steepening of the corneal curvature, corneal edema deposits may be found on the endothelium or less fromhypoxia, and decreased aqueous component of capsule and may occur (30). the pre-corneal tear film that leads to dry eye (5) 1) Antipsychotics- Use of these drugs leads to Micro-vascular complications may be related to blurred vision decreasedaccommodation and changes in retinal vasculature, enhanced platelet (2). These symptoms are transient and dose- adhesiveness, or increase in fibrinogen and clotting dependent. Reduced tearing and dry eye may also factors (5). result from the anticholinergic effects. 3) HormoneEJMR replacement therapy (HRT) with a) Chlorpromazine- Chlorpromazine, at high Progesterone- Hormone receptor sites are located on dosages, can commonly cause abnormal pigmentation meibomianglands. Physiological changes can cause of the , inter-palpebral and cornea. alterations in the tear film, causing dry eye and contact It can also cause a more worrisome but rare visual lens intolerance, which are common side effects of this impairment, namely corneal oedema (31) medication. Abnormal vision, visual disturbances and are generally the effects observed with this Fig 4: No corneal endothelial deposits seen associated drug (25). with lenticular deposits (32). 4) Leuprolide acetate(Lupron) -Administration of Pigment deposits can occur on areas of the bulbar conjunctiva that are exposed to UV radiations. ERA’S JOURNAL OF MEDICAL RESEARCH, VOL.6 NO.1 Page: 4 Jan - Jun 2019 ERA’S JOURNAL OF MEDICAL RESEARCH VOL.6 NO.1

UVprotection was found unsuccessful to reduce the 2) Antianxiety drugs prevalence and these patients should simply be Ocular side effect like blurred vision and diploma are monitored on a yearly basis. Also, retinal and macular usually rare and revesiblewith antianxiety drugs (24). damage have been reported in higher doses (24). This can Use of diazepam (Valium) sometimes produces lead to permanent visual acuity and loss if not mydriasis. may onset after 30 closely monitored. However, some of these changes may minutes due to antigenic factors in the drug (2). be reversible if detected early, with discontinuation of drugs or giving symptomatic medication. 3) Antidepressants It can cause transient and reversible symptoms of blurred visionmainly due to the anticholinergic effect of these medications and is usually a consequence of both and mydriasis (30, 33). Clinicians should use caution with sympatho-mimetics along with tricyclics and also with monoamine oxidase (MAO) inhibitors. TCAs can induce glaucomatous attacks in predisposed individuals. This is mainly due tothe anti-cholinergic action of these medications, and to the subsequent mydriasis and cycloplegia (34). SSRIs have been associated with mydriasis,increased IOP and angle-closure glaucoma (35,36). The explanation for these adverse effectscould be derived from the multiple action of SSRIs, with inter- individual variations, culminatingin a pupillary dilatation and a relative blockade of the angle of the anterior chamber viaanticholinergic or noradrenergic effects, and serotonergic effects (37). SSRIs may cause mydriasis via at least two mechanisms: 1. noradrenergic or anti-cholinergic effects resulting in pupillary dilatation; 2. stimulation of the 5-HT7 Fig 3: Stellate Pattern of Lenticular Deposits (21) receptors located within the iris musculature and the subsequent relaxation of the sphincter muscle of the a) Lithium- Lithium has been reported to cause (33). downbeat jerk which may not even be reversed when the drug is stopped (4). Blurred vision 4) Sedatives sometimes occurs due to cortical involvement. Other In patients using barbiturates, , diplopia and ocular complications include, keratitis sicca, contact lens nystagmus are commonly noticed (38). intolerance and diplopia. One bothersome potential 5) Anticonvulsants adverse effect of lithium is eye irritation, usually noted Phenytoinand carbamazepine are very commonly during the first few weeks of treatment (16). The prescribed as anticonvulsant, which may cause explanation behind this uncommon finding could be the abnormal colour , nystagmus (39). increased sodium content of the lacrimal fluid, a Carbamazepine works by inhibiting voltage- phenomenon probably related to the presence of sodium- dependent sodium channels (40). It commonly chloride co-transport in human lens epithelial cells, as induces diplopia and gaze-evoked nystagmus, but it recently demonstrated by Lauf et al. (18) This problem is rarely leads to gaze palsies, downbeat or periodic usually shortlived and can be resolved even faster if the alternating nystagmus (41-42). patient usesEJMR over-the-counter artificial tears as needed. 6) CNS Stimulants are reported to cause b) Phenothiazines: The most commonly accommodative dysfunctions and blurred vision due documented retinal lesion secondary to to mydriasis (43). phenothiazines is pigmentary retinopathy. Phototoxic processes are believed to be involved in both 7) Antimigraine Agents pigmentary retinopathy and retinal degeneration. it is Not many side effects have been found with postulated that antipsychotics, by their anti- antimigraine agents. However corneal opacities were dopaminergic actions, tend to prevent the beneficial reported in dogs with newer drugs. Thus, it is best to effect of dopaminergic mechanisms on the life- take a careful history and monitor any changes (2). regulatory functions of retinal tissues (30). ERA’S JOURNAL OF MEDICAL RESEARCH, VOL.6 NO.1 Page: 5 OCULAR SIDE EFFECTS OF SYSTEMIC DRUGS

Topiramate is a drug used for epilepsy and migraine opacitiesresembling chloroquine keratopathy and prophylaxis. It causes acute transient myopia with blurred vision, especially when used long term. shallowing of the anterior chamber which is a rare Symptoms associated with the corneal opacities can idiosyncratic response (44). range from mild light sensitivity to frank . The dystonic effects of certain psychotropic These corneal changes diminish or disappear within 6 medications (antipsychotics, carbamazepine, months of discontinuing indomethacin (47). topiramate and possibly escitalopram) are of common H) PulmonaryDisease Drugs concern in psychiatry. More often than not, they are of 1) Steroids- acute onset, but cases of tardive dystonia are also well documented in the literature (45). Acute dystonias Inhalers have been linked to posterior and sub capsular have a complex aetiology; they can be secondary cataracts, delays corneal healing, increased intraocular pressure and exacerbation of glaucoma in susceptible todopamine receptor blockade, but other mechanisms 7 are likely to play a role as well. individuals. Glucocorticoid-induced gene transcription events in lens epithelial cells, and also other intraocular or F) Anti-Malaria medications systemic cells, likely interact to generate steroid cataracts Antimalarial drugs like Chloroquine and (8). It causes stabilization of lysosomal membranes and Hydroxyxhloroquine have visual side effects of accumulation of polymerized glycosamino-glycans decreased , corneal whorls and (GAGs) in the trabecular meshwork, they become scotomas. Ocular side effects include a “bull's-eye” hydrated, producing "biologic edema" and increased with attenuated retinal vessels. Patients outflow resistance, leading to increased intraocular may have a yellow, green or blue tinge to their visual pressure and glaucoma (9-10). 2 field with colored halos around light The pathogenesis of steroid-induced cataract may Hydroxychloroquine binds to melanin, accumulates in involve multiple mechanisms. One mechanism that is the RPE, and remains there for long periods of time. It proposed for the corticosteroid-induced PSC is the is directly toxic to the RPE, causing cellular damage formation of covalent adducts of the steroid molecule and atrophy. This occurs due to disruption of RPE with the lysine residues of lens particles resulting in metabolism, specifically from lysosomal damage, and lens opacities (48). Another proposed mechanism is reduced phagocytic activity toward shed the inhibition of the sodium–potassium pump in the photoreceptor outer segments. Accumulation of lens epithelium, leading to an accumulation of water photoreceptor outer segments leads to RPE within the lens fibres and agglutination of lens degeneration, migration into the outer retina, and proteins. Other theories postulate that PSC finally photoreceptor loss (46). development secondary to corticosteroid use involves Transients and reversible corneal changes occur elevation of glucose in the plasma and aqueous humor, typically when patient receives more than 250g daily increased cation permeability, inhibition of glucose-6- (31). It is important for all patients on this medication phosphate dehydrogenase, inhibition of ribonucleic to get a baseline visual field and fundus examination acid synthesis, and loss of lens ATP. It is therefore with routine follow ups. plausible that multiple mechanisms are responsible for G) Rheumatological drugs the development of PSC in patients treated with corticosteroids (47). NSAIDS like ibuprofen and indomethacin have visual side effects that include vision changes, , 2) Mast Cell Stabilizers- photophobia, diplopia, color vision changes and rarely · Nedochromyln sodium (Inhaler Tilade) has been toxic optic neuropathy. Adverse ocular reactions associated with conjunctivitis (49). include corneal vortex keratopathy(indomethacin), 3) Antituberculosis Medications pseudotumour cerbri, optic neuritis and macular edema.6CasesEJMR of retinopathy have been associated An uncommon but serious complications of anti with NSAIDs and especially indomethacin due to tuberculosis drug therapy is acquired optic neuropathy (24). pigmentary changes of the macula and other areas of a) Isoniazid and Ethambutol can cause retro-bulbar the retina causing symptoms of blurred vision. optic neuritis (43)causing blurred vision, decreased Depending on the amount of retinal involvement, the visual acuity, central scotomas, and loss of red-green electroretinogram (ERG) and electrooculogram color vision (50). Although uncommon at standard (EOG) can be normal or abnormal (47). doses, optic neuritis is the most important potential Indomethacin is one of the most potent NSAIDs that side effect of thambutol. Retrobulbar neuritis is the has been associated with cases of corneal most common, with involvement of either the axial

ERA’S JOURNAL OF MEDICAL RESEARCH, VOL.6 NO.1 Page: 6 Jan - Jun 2019 ERA’S JOURNAL OF MEDICAL RESEARCH VOL.6 NO.1 fibers or less commonly peri-axial fibers, and a mixed 5. Bartlett JD. Ophthalmic toxicity by systemic pattern on occasion (48,51). Mitochondrial drugs. In : GCYChiou,ed Ophthalmic dysfunction leading to optic neuropathies is getting Toxicology, 2nd ed. Michigan:Taylor and Francis, recognized a lot more as a spectrum of conditions that 1999:225-83. reach a similar end point (48,52). 6. Maus M. Ocular manifestations of systemic b) Ethambutol (Myambutol), Rifampicin disease. Curr Opin Ophthalmol. 1998;9(6):61-63. (Rifadin), Isoniazid( Nydrazid), which has been 7. Fan D. Ocular-Hypertensive and Anti- associated with complaints of transient and reversible inflammatory Response to Rimexolone Therapy accommodation impairments (53). i n C h i l d r e n . A r c h . O p h t h a l m o l . c) Rifampicin: produce conjunctivitisand orange 2003;121(12):1716. staining of contact lenses (54). Thesediscolorations 8. James ER. The Etiology of Steroid Cataract. J may be bothersome to the patient butdo not require Ocul Pharmacol Ther. 2007;23(5):403–20. medical attention. 9. Francois J. Tissue culture of ocular fibroblast. I) Decongestants Ann Ophthalmol. 1975 Dec;7(12):1551–1554. · Phenylephrine- may cause rebound miosis and 10. F r a n c o i s J , Vi c t o r i a - T r o n c o s o V. decrease mydriasis (54) Mucopolysaccharides and pathogenesis of J) Bisphosphonates cortisoneglaucoma. Klin Monatsbl Augenheilkd. Fosamax,a bisphosphonate that is prescribe for post 1974 Jul;165(1):5–10. menopausal women to prevent calcium bone loss,can 11. Peponis V, Kyttaris VC, Chalkiadakis SE, cause orbital inflammation, and (55). Bonovas S, Sitaras NM. Ocular side effects of The proposed mechanism of ocular inflammation is an anti-rheumatic medications: what a idiosyncratic γΔ T cell cytokine release involving IL-1 rheumatologist should know. Lupus. and IL-6 caused by bisphosphonates' similar structure 2010;19(6):675–682. to pyrophosphate molecules (56,57). 12. Sandhya N. Ocular adverse effects of common CONCLUSION systemic medications. Kerala JOphthalmol. It can be concluded that many systematic drugs can 2012;24:27–39. produce ocular and visual side effect which range from 13. Yilmaz S, Tuncer E, Alioglu E, Dereli T, Turk U, mild to severe and can be even vision threatening. A Turk B. Amiodarone-induced multiorgan toxicity careful and detailed case history is necessary to be with ocular findings on confocal microscopy. aware of patient's medical history. It is very important Middle East Afr J Ophthalmol. 2015;22(2):258. that these ocular side effects from systemic drug use be 14. Moorthy RS. Valluri S. Ocular toxicity associated reported and addressed timely. with systemic drug therapy. Opin Ophthalmol. These visual side effects should be recognized at the 1999;10(6):438-46. earliest to minimize serious complications and to plan 15. Jaanussd, Barlett JD, Hiefr JA. Ocular effects of appropriate intervention by modification of dosage or systemic drugs In :Barlett JD and Jaanus SD use of alternative drugs. .Clinical Ocular pharmacology 3rd ed. Bostan: REFERENCES Butterworth. Heinemann. 1995:957:1006 1. Blomquist P, Palmer B. Ocular Complications of 16. Anticoagulants/antiplatelets/antithrombotics. Systemic Medications. The Am J Med Sci. Reactions Weekly. 2019;1751(1):38-38. 2011;342(1):62-69. 17. Wymore J, Carter J. Chlorpropamide-Induced 2. Wren V.Q.Ocular & Visual side Effects of Optic Neuropathy. Arch Intern Med. systemicEJMR Drugs- Clinically Relevant Toxicology 1982;142(2):381-381. and patient Management. J.Behav.Optom. 18. Fraunfelder FF. Drug-induced ocular side effects. 2000:11(6):149. Folia Ophthalmol JPN. 1996;47(7):770-73. 3. Mycek MJ, Harvey RA, Champe PC Lippincott's 19. Paterson C. Effects of Drugs on the Lens. Int I I I u s t r a t e d R e v i e w s : P h a r m a c o l o g y, Ophthalmology Clinics. 1971;2(2):63-98. 2nded.phladelphia:Lippincott-Raven, 1997. 20. Novack G. Ocular toxicology. Curr Opin 4. Gaudana R, Ananthula H, Parenky A, Mitra A. Ophthalmol. 1994;5(6):110-14. Ocular Drug Delivery. The AAPS Journal. 2010;12(3):348-360. 21. Reviewofoptometry. Cataracts secondary to

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medication are usually asymmetric, perhaps due Effect of fluoxetine on intraocular pressure in the to unequal deposition of medication in the rabbit. Exp Eye Res 2000 May; 70 (5): 551-5 crystalline lens. [image on internet] Published , 37. Schmitt JA,Riedel WJ,Vuurman EF,et 2016January 15 [cited 2019 june 22] available al.Modultion of the critical flicker fusion effects from https://www.reviewofoptometry. of serotonin reuptake inhibitors by concomitant c o m / a r t i c l e / t h e - m i n d s - e y e - o c u l a r - pupillary changes.Psychophrmacy (Berl)202 complications- of-psychotropic-medications Apr;160(4):381-6 22. C h y l a c k LT. C a t a r a c t s a n d i n h a l e d 38. Peragallo J,Biousse V,Newman N.Ocular coreticostroids. N Eng J med 1997:337:46-8 manifestations of drugs and alcohol abuse. Curr 23. Krishnaswami A, Ravi-Kumar S, Lewis JM. Opin Ophthalmol.2013;24(6):566-73 Thiazolidinediones: a 2010 perspective. Perm J. 39. Roff Hilton E,Hosking S,Betts T.The effect of 2010;14(3):64–72. a n t i e p i l e p t i c d r u g s o n v i s u a l 24. LevineL.Optometrically relevant side effects of performance.Seizure.2004:13(2):113-28. the systemic drugs most frequently prescribed in 40. Jo S, Bean BP.Sidedness of carbamazepine 1991.J Behav Optome 1992:3(5):115-19. accessibility to voltage-gated sodium 25. Schaumberg D. Hormone Replacement Therapy channels.Mol Pharmacol. 2014 Feb;85(2):381-7. a n d D r y E y e S y n d r o m e . J A M A 41. Hadjikoutis S,Morgan JE,Wild JM,et al.Ocular 2001;286(17):2114. complications of neurological therapy.Eur J 26. Fraunfelder FT, Edwards R. Possible Ocular Neurol 2005 Jul;12(7):499-57ssssss Adverse Effects Associated With Leuprolide 42. Chrousos GA ,Cowdry R,Schuelein M, et al.Two Injections. JAMA. 1995;273(10):773–774. cases of downbeat nystagmus and 27. Zaman F, Bach C, Junaid I, et al. The floppy iris associated with carbamazepine.Am J Ophthalmol syndrome - what urologists and ophthalmologists 1987;103:221-4 need to know. Curr Urol. 2012;6(1):1–7. 43. To HT,Townsend JC.Ocular toxicity of systemic 28. Chang DF, Campbell JR. Intraoperative floppy medications:a case series .J Am Optom Assoc iris syndrome associated with tamsulosin. J 2000;711:29-29 Cataract Refract Surg. 2005;31:664–673. 44. D e s a i C M , R a m c h a d a n i S J , B h o p a l e 29. Laties A1, Zrenner E. Viagra (sildenafil citrate) SG,Ramchandani SS.Acute myopia and angle and ophthalmology. Prog Retin Eye Res. 2002 closure caused by topiramate,a drug used for Sep;21(5):485-506. p r o p h y l a x i s o f m i g r a i n e . I n d i a n J 30. Richa S, Yazbek J. Ocular Adverse Effects of Ophthalmol.2006;54:195-7 Common Psychotropic Agents. CNS Drugs. 45. Hansen TE,Casey DE,Hoffman WF.Neuroleptic 2010;24(6):501-526. intolerance. Schizophr ull 1997;23(4):567-82 31. Hansen TE, Casey DE, Hoffman WF. Neuroleptic 46. Yam JC,Kwok AK.Ocular toxicity of intolerance. Schizophr Bull 1997; 23 (4): 567-82 hydroxychloroquine.Hong Kong MedJ.2006 32. Jain D, Arunan SM, Vedachalam A.Anterior Aug:12(4):294-304 Segment Involvement in Antipsychotics - An 47. Peponis V,Kyttaris VC,Chalkiadakis Unusual Presentation.DJO 2018;29:68-69. SE,Bonovas S,Sitaras NM.Ocular side effects of 33. Malone Jr DA, Camara EG, Krug Jr JH. a n t i r h e u m a t i c m e d i c a t i o n s : w h a t a Ophthalmologic effects of psychotropic r h e u m a t o l o g i s t s h o u l d k n o w. L u p u s medications. Psychosomatics 1992 Summer; 33 2010;19(6);675-682 (3): 271-7EJMR48. C h y l a c k LT. C a t a r a c t s a n d i n h a l e d 34. Ritch R, Krupin T, Henry C, et al. Oral corticosteroids.N Engl J Med.1997;337:46-48 imipramine and acute angle closure glaucoma. 49. Castillo M, Scott NW, Mustafa MZ, Mustafa MS, Arch Ophthalmol 1994; 112 (1): 67-8 Azuara-Blanco A.Topical antihistamines and 35. Costagliola C, Parmeggiani F, Sebastiani A. mast cell stabilisers for treating seasonal and SSRIs and intraocular pressure modifications: perennial allergic conjunctivitis.Cochrane evidence, therapeutic implications and possible Database Syst Rev. 2015 Jun 1;(6):CD009566. mechanisms. CNS Drugs 2004; 18 (8): 475-84 50. Kokkada SB, Arthakur R,Nataranjan M,Palaian 36. Costagliola C, Mastropasqua L, Capone D, et al. S,Chhetri AK,Mishra P.Ocular side effects of ERA’S JOURNAL OF MEDICAL RESEARCH, VOL.6 NO.1 Page: 8 Jan - Jun 2019 ERA’S JOURNAL OF MEDICAL RESEARCH VOL.6 NO.1

ntitubercular drugs-a focus on prevention, early Phenlephrine Hydrochloride.Am J.Med detection and management .Kathmandu Univ 1970;70(5):72-33 Med J.2005 Oct-Dec ;3(4):438-41 55. Umunakwe O.Diffuse ocular and orbital 51. Koul Pa.Ocular toxicity and ethambutol inflammation after zoledronate infusion-case theraphy:Timely recaution.Lung India report and review of the literature. Digit 2015;32(1):1-3. J.Ophthalmol.2017;23(4):18 52. Chen L,Liang Y. neuropathy by 56. McClung M, Harris ST, Miller PD, Bauer DC, ethambutol toxicity.Zhonghua Jie He HE Xi Za Davison KS, Dian L, et al. Bisphosphonate Zhi 1999;22:302-4 therapy for osteoporosis: benefits, risks, and drug 53. Jimenez Lucho VE,del usto R,Odel J. Isoniazid holiday.Am J Med. 2013 Jan;126(1):13-20. and ethambutol as cause of optic neuropthy.Eur J 57. Kunzmann V,Bauer E,Wilhelm M.Gamma/delta Respir Dis 1987;70(5):729-33 T- cell stimulation by pamidronate.N Engl J Med 54. Haddad N,Moyer N,Riley F.Mydriatic effect of 1999;340:737-38SS

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