Side Effects Of Systemic Drugs

Hydroxychloroquine/Chloroquine

• Many drugs possess a high affinity for binding melanin (by Van der Waals’ forces). Other examples are beta-blockers and benzodiazepines

• Chloroquine and hydroxychloroquine are toll-like receptor inhibitors

• They concentrate in the melanin of the RPE and accumulate causing local photoreceptor toxicity

  • Leads to perifoveal photoreceptor loss: bull’s eye maculopathy (with foveal cone sparing)

• High-doses of drug-melanin complexes are toxic to the retina, typically more than 100g total dose for more than a year is needed.

• As such the effect is dose-dependent

• Hydroxychloroquine is much safer with little risk of retinopathy if the dose is <400mg/day

  • Used in RA and SLE: better side effect profile than other DMARDs and does not need serological monitoring
  • Updated 2018 RCOphth guidelines recommend a maximum dose of 6.5mg/kg/day of ideal body weight

College screening guidelines: annual monitoring of patients on HCQ or CQ

• No risk factors: start screening after 5 years
• Risk factors (CQ use, concomitant tamoxifen, renal impairment, or dose >5mg/kg/day): start screening after 1 year
  • Screen using: SD-OCT, 10-2 HVF and FAF first. If one test abnormal (possible toxicity), consider mfERG but continue treatment
  • If definite toxicity (two tests abnormal): recommend to prescribing physician that treatment be stopped (but not appropriate for ophthalmologist to stop the treatment).

Presentation

• Bilateral paracentral scotomas
• Photopsia
• Reduced colour vision
• Advanced: narrowed arterioles, disc pallor, retinal granularity

Photosensitising agents

• Absorb visible and UV radiation and generate free radicals
• Such agents may become bound in the cornea, lens and retina
• Examples
  • Amiodarone
  • Phenothiazones
  • Psoralens

Drug induced angle closure

• Topiramate
• Methylphenidate
• SSRIs
• Tricyclic antidepressants

Drug induced myopia

• Acetazolamide
• Oral contraceptive
• Tetracyclines
• Pilocarpine due to ciliary muscle contraction
• Topiramate: used for epilepsy and migraine
  • Also causes: suprachoroidal effusion, angle-closure (through swelling and anterior rotation of the ciliary body), scleritis, oculogyric crisis
  • Managed by stopping topiramate and cycloplegia

Optic neuropathy

• Ethambutol
• Streptomycin
• Chloramphenicol
• Isoniazid
• Amiodarone
• Hydroxychloroquine
• Cisplatin and vincristine

Cystoid macular oedema (toxic macular oedema)

• Tamoxifen (crystalline maculopathy)

  • A selective oestrogen receptor modulator
  • Causes: corneal changes, cataract and optic neuropathy as well as perifoveal crystalline deposits and cystoid changes
  • Current standard lower doses of 20-40mg/day have <1% adverse effects
  • Treatment should be stopped in consultant with oncologist and patient if cystoid maculopathy develops as vision loss can occur.

• Rosiglitazone

• Epinephrine

• Latanoprost

• Niacin

• Fingolimod

• MEK inhibitors (used for cancers such as metastatic melanoma)

Raised intracranial pressure (drug-induced IIH)

• Tetracyclines
• Fluoroquinolones
• Retinoids (vitamin A)
• Progesterones (oral contraceptive)
• Corticosteroids
• Amiodarone
• Lithium
• Phenytoin
• Tamoxifen

Vigabatrin

• Used for partial epilepsy often in children
• Causes bilateral, concentric, nasal constriction of the visual field with temporal and macular sparing
• Typically irreversible despite stopping the drug
• M>F
• Visual field screening should be done with either Humphrey (ideally Humphrey Supra-threshold 120 degree full field test) or Goldmann
  • If no defects found, patients can be screened 6-monthly for 5 years then annually
  • Screening allows for cessation of the drug before symptomatic

Antifibrotics table

	5-FU	MMC
Mechanism of action	Competitively inhibits thymidylate synthetase in S phase cells: inhibits DNA synthesis.Metabolites render DNA unstable	Alkylating agent: cross links DNA
Active stage	S phase and G2	Any stage (especially G and S)
Fibroblast inhibition	4-6 weeks	Permanent. 100 times more potent
Adverse effects	Corneal epithelial toxicity Hypotonous maculopathy Suprachoroidal haemorrhage Conjunctival wound leak Ischaemic blebs	Higher risk of hypotony and wound leak (as more potent than 5-FU)

Serum drops

• Adjunct for ocular surface disease

• Provide nutritional molecules and epitheliotrophic component including immunoglobulin

• Promote epithelialisation

• Currently unlicensed and so can only be prescribed as a special need

  • Can only be used after licensed treatments have been tried

• College guidelines on groups who benefit

  • Severe ocular surface disease

    • Sjogrens
    • MMP
    • SJS

  • Persistent/recurrent epithelial defects

  • Neurotrophic keratopathy, including

    • Diabetic neuropathy
    • Herpes zoster
    • CN-V dysfunction

  • Supportive cases

    • Exposure keratopathy eg. for patients in intensive care
    • Severe ocular surface injury eg. chemical/thermal burns

• Autologous serum: from patients own blood

• Allogeneic serum: from male volunteer. For patients unfit to donate or who require urgent treatment.

• Prescribed as 50% dilution in 0.9% normal saline