## 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 &lt;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 &lt;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

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


## 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


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

Pharmacology

Side Effects Of Systemic Drugs

Intro

FRCOphth Part 2 Study Notes

Tumours, masses and neoplasia

Tumours overview

Uveitis

Uveitis background

Anterior uveitis

Intermediate uveitis

Uveitis in JIA

Uveitis with JIA

Retinal vasculitis

Sarcoidosis

Behcet's disease

Toxoplasmosis

Viral uveitis

Strabismus

Overview

Esotropia

Fungal uveitis

Mycobacterial uveitis

Adnexal masses

Spirochaetal uveitis (including Syphilis)

Exotropia

Melanoma

Nematode uveitis

Retinoblastoma

Retinoblastoma (for Part 2)

Incomitent

Voyt-Koyanagi-Harada syndrome

Conjunctival intraepithelial neoplasia

Vertical deviations

Sympathetic ophthalmia

Orbit and ocular adnexae

Orbit

AV Malformations and hamartomas

Arteriovenous malformations and hamartomas

Restriction syndromes

Paediatrics

Leucocoria

Congenital Cataract

Paediatric Glaucoma

Retinopathy of prematurity

Retinopathy of Prematurity

ROP-like disorders

Congenital nasolacrimal duct obstruction

White dot syndromes

Aniridia: Short Arm 11 Deletion (11p13)

Choristomas

Management Of Amblyopia

Alphabet patterns

Scleritis

Iris Nodules

Meningioma

Strabismus surgery

Optic nerve glioma

Lymphoma

Extraocular Muscles

Rhabdomyosarcoma

Idiopathic orbital inflammation

Orbital neuroblastoma

Anterior Persistent Foetal Vasculature

Lacrimal system

Metastatic lesions

Surgical Retina

Retinal Detachment

Vitreoretinal Interface And Macular Hole

Epiretinal Membrane

Medical Retina

Diabetic Eye Disease

Orbital Blood Vessels

Retinal Vascular Disease

Macular Degeneration

Central Serous Chorioretinopathy (CSCR)

Sickle Cell Retinopathy

Retinitis Pigmentosa

Albinism

Retinal Telangiectasias

Miscellaneous Retinopathies

Atropine And Myopia Progression

Foetal Alcohol Syndrome

Neuro-ophthalmology

Optic Neuropathy

Papilloedema

Idiopathic Intracranial Hypertension

Chiasmal Disorders

Retrochiasmal Disorders

Migraine

Paranasal Sinuses

Supranuclear Motility Disorders

Third Nerve Palsies

Fourth Nerve Palsies

Sixth Nerve Palsies

Seventh Nerve Palsies

Anisocoria

Myasthenia Gravis

Myopathies

Blepharospasm

Functional Visual Loss

Lacrimal Glands

Phakomatoses

Developmental diseases

Tear Film

Eyelids

Blinking

Lid Malpositions

Anterior segment - ocular surface

Conjunctiva

Conjunctivitis

Sclera

Pigmented Conjunctival Lesions

Squamous Cell Carcinoma Of The Conjunctiva

Ocular Cicatricial Pemphigoid

Cornea

Corneal Structure And Development