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Drugs in Ophthalmology - Postgraduate MD Ophthalmology Exam Notes- Dr. Prabhat Devkota, MD.pdf

Drugs in Ophthalmology – Postgraduate MD Ophthalmology Exam Notes Author: Dr. Prabhat Devkota, MD This book is a concise, high-yield review of ophthalmic pharmacology designed for MD/MS/DNB Ophthalmology residents, fellows, practicing ophthalmologists, and postgraduate exam candidates. It provides exam-oriented notes with simplified mechanisms of action, indications, dosages, adverse effects, contraindications, drug classifications, and important clinical pearls presented in an easy-to-revise format. The notes cover topical and systemic ophthalmic medications, antimicrobial agents, antivirals, antifungals, corticosteroids, cycloplegics, mydriatics, antiglaucoma drugs, anti-VEGF agents, immunosuppressants, biologics, ocular lubricants, fortified eye drops, and recent advances in ophthalmic therapeutics. Important clinical trials, viva points, mnemonics, and high-yield tables are included to facilitate rapid revision before postgraduate examinations. This resource is intended as a practical companion for daily clinical practice, ward discussions, journal clubs, viva voce, and university examinations. Who should read this book? MD/MS/DNB Ophthalmology residents FCPS and fellowship trainees Practicing ophthalmologists Medical officers preparing for postgraduate entrance or exit examinations Anyone seeking a concise review of ophthalmic pharmacology If you find this book helpful, please share it with colleagues and students to support ophthalmology education. Keywords: Ophthalmology, Ophthalmic Drugs, Pharmacology, MD Ophthalmology, MS Ophthalmology, DNB Ophthalmology, PG Notes, Eye Drugs, Antiglaucoma Drugs, Anti-VEGF, Immunosuppressants, Biologics, Corticosteroids, Ophthalmology Viva, Ophthalmology Exam Notes, Clinical Ophthalmology. #DrugsInOphthalmology #OphthalmologyDrugs #OphthalmologyPharmacology #MDOphthalmology #MDOphthalmologyNotes #PostgraduateOphthalmology #OphthalmologyExam #OphthalmologyExamNotes #OphthalmologyNotes #OphthalmologyResident #OphthalmologyViva #OphthalmologyRevision #HighYieldOphthalmology #HighYieldNotes #OphthalmologyPDF #FreeOphthalmologyPDF #MedicalNotes #MedicalEducation #OphthalmicPharmacology #OcularPharmacology #EyeDrops #OphthalmicDrugs #Antibiotics #Antivirals #Antifungals #Steroids #NSAIDs #GlaucomaDrugs #Mydriatics #Cycloplegics #AntiVEGF #OcularTherapeutics #ClinicalOphthalmology #PostgraduateMedicalEducation #DrPrabhatDevkota

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PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 1 | P a g e drprabhatdevkota@gmail.com Postgraduate Ophthalmology Exam Notes © First Edition, 2026 Author Dr. Prabhat Kiran Devkota, MBBS(TU), MD(NAMS) MBBS – Chitwan Medical College Teaching Hospital, Institute of Medicine, Tribhuvan University (TU), Nepal MD (Ophthalmology) – Lumbini Eye Institute & Research Center, National Academy of Medical Sciences (NAMS), Nepal Email: drprabhatdevkota@gmail.com All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, transmitted, or distributed in any form or by any means, whether electronic, mechanical, photocopying, recording, or otherwise, without prior written permission of the author, except for brief quotations used for academic, educational, or review purposes. Disclaimer This book is intended solely as an educational and revision resource for postgraduate ophthalmology trainees and practitioners. While every effort has been made to ensure the accuracy and reliability of the information presented, the author does not guarantee that all content is free from errors or omissions. Readers are encouraged to consult standard textbooks, peer-reviewed literature, institutional guidelines, and current evidence-based recommendations before making clinical decisions. The author shall not be held responsible for any consequences arising from the use of information contained in this book.
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 2 | P a g e drprabhatdevkota@gmail.com Preface This book is a compilation of notes gathered during my preparation for the Final MD Examination in Ophthalmology. The material has been collected from standard textbooks, lecture notes, journals, online resources, and personal study notes. Topics have been organized in a chapter-wise format to facilitate quick revision and easy reference. Although there are many excellent ophthalmology resources available, I felt it worthwhile to compile and share these notes with future ophthalmology trainees and colleagues. This work represents a continuous learning process rather than a definitive textbook. Suggestions, corrections, contributions, and constructive feedback are greatly appreciated and will help improve future editions. I sincerely hope this book serves as a useful companion in your postgraduate ophthalmology journey. Good Luck and Best Wishes! For comments, suggestions, or contributions, please contact: Dr. Prabhat Devkota, MD drprabhatdevkota@gmail.com
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 3 | P a g e drprabhatdevkota@gmail.com CONTENTS SN Topic 1 Ophthalmic Drug Delivery 2 Cycloplegics 3 Mydriatics 4 Corticosteroids 5 General Principles of Preparation 8 Antibacterial Agents 9 Antifungal Agents 10 Antiviral Agents 11 Antiglaucoma Medications 12 Anti-VEGF Drugs 13 Immunosuppressive Therapy (IMT) 14 Sodium Chloride (Hypertonic Saline) 15 Antiallergic Drugs 16 Local Anesthetics 17 Botulinum Toxin (Botox) 18 Mitomycin-C (MMC) 19 5-Fluorouracil (5-FU) 20 Ophthalmic Viscosurgical Devices (OVDs) 21 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) 22 Tear Supplements
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 4 | P a g e drprabhatdevkota@gmail.com OPHTHALMIC DRUG DELIVERY Topical Administration Most common, noninvasive, self-administered. Limitations: Rapid systemic absorption via conjunctival/episcleral vessels & nasolacrimal drainage. Limited posterior segment penetration. Forms • Solutions: easy, minimal vision interference, short contact time. • Suspensions: require shaking, variable resuspension, may clog droppers (esp. prednisolone acetate 1%). • Ointments: prolonged contact, act as reservoir, blurred vision, preferred for bedtime dosing or corneal ulcers. • Gels / In situ gels: sustained contact, reduced frequency (e.g., timolol gel). • Sprays: noninvasive, useful in children, closed eyelid administration. • Unit-dose dispensers: preservative-free, short-term use. • Special Devices • Soft contact lenses: prolonged delivery; water content affects absorption. • Collagen shields: dissolve over 12–72 hrs; release drug gradually. • Filter paper strips: fluorescein, lissamine green, rose bengal; precise dosing. • Cotton pledgets: prolonged local exposure for mydriatics. • Continuous irrigation / Morgan lens: for large volumes (chemical burns). Periocular Administration Routes: subconjunctival, sub-Tenon’s, retrobulbar, peribulbar. Advantages: high local concentration, low systemic absorption. Route Indication / Notes Subconjunctival Antibiotics for corneal ulcers, corticosteroids, anesthesia, antifibrotics post-trabeculectomy Sub-Tenon’s (posterior) Chronic posterior uveitis, CME, DME, steroid depot (Anecortave) Retrobulbar Mainly anesthesia; occasional steroids, alcohol; risk: globe perforation, hemorrhage Peribulbar Safer alternative to retrobulbar; avoids muscle cone; similar anesthesia, slower onset Complications: hemorrhage, ecchymosis, proptosis, optic nerve injury, retinal artery occlusion, cardiovascular events.
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 5 | P a g e drprabhatdevkota@gmail.com Intracameral Administration Direct anterior chamber delivery. • Indications: viscoelastic, lidocaine anesthesia, tissue plasminogen activator, sustained-release steroid pellets (Surodex). • Reduces systemic exposure, high local effect. Intravitreal Administration • Direct vitreous delivery; bypasses blood–ocular barrier. • Indications: • Antibiotics / antifungals → bacterial/fungal endophthalmitis. • Antivirals → CMV retinitis (Vitrasert implant, ganciclovir). • Corticosteroids → diabetic macular edema, noninfectious posterior uveitis (Retisert, triamcinolone). • Anti-VEGF →AMD (ranibizumab, pegaptanib, aflibercept). • Advantages: high posterior drug levels, minimal systemic toxicity. • Complications: retinal detachment, vitreous hemorrhage, endophthalmitis. Key Exam Pearls • Topical drugs rarely reach posterior segment. • Nasolacrimal occlusion increases intraocular absorption and reduces systemic effects. • Ointments → prolonged contact; blur vision → use at night. • Sprays can achieve effective drug delivery on closed eyelids. • Subconjunctival antibiotics → corneal ulcers; posterior sub-Tenon’s steroids → macular edema. • Vitrasert → sustained ganciclovir for CMV retinitis. • Morgan lens → continuous irrigation for chemical burns.
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 6 | P a g e drprabhatdevkota@gmail.com CYCLOPLEGICS ATROPINE Class: Naturally occurring alkaloid, nonselective muscarinic antagonist Source: Atropa belladonna (belladonna plant) Topical ophthalmic: 1% solution and 1% ointment Mechanism ofAction (MOA) Nonselective M3 muscarinic receptor antagonist → blocks parasympathetic input Effects in the eye: Mydriasis: relaxes sphincter pupillae Cycloplegia: paralyzes ciliary muscle → prevents accommodation Duration: Mydriasis: up to 10 days Cycloplegia: 7–12 days Pharmacokinetics Parameter Value / Notes Onset of mydriasis 12 min Max mydriasis* 26 min Return to normal pupil 10 days Cycloplegia onset 12–18 min Max cycloplegia* 106 min Return of accommodation 42 h–8 days Systemic absorption Rapid via conjunctival vessels & nasal mucosa, plasma peak ~10 min Clinical Uses A. Cycloplegic Refraction: Gold standard for cycloplegic refraction in children with suspected latent hyperopia or accommodative esotropia Reveals more hyperopia than shorter-acting agents B. Uveitis /Anterior Uveal Inflammation Relieves ciliary spasm → reduces pain Prevents posterior synechiae → reduces risk of iris bombé Reduces aqueous flare and cell accumulation C. Myopia Control (ATOM) Relaxes ciliary muscle → reduces axial elongation 0.1% atropine: slows progression (<0.5 D decrease per year vs 0.9 D increase untreated)
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 7 | P a g e drprabhatdevkota@gmail.com D.Amblyopia (Pharmacologic Penalization) Cycloplegic blur in better eye → forces use of amblyopic eye Used for moderate/mild amblyopia (VA>20/100) E. Other Uses: Malignant Glaucoma, NVG, Corneal Ulcer/keratitis Systemic Uses: • Symptomatic bradycardia – increases heart rate by blocking vagal stimulation. • Organophosphate / carbamate poisoning – antagonizes muscarinic effects (salivation, bronchorrhea, bradycardia). • Pre-anesthetic / during anesthesia – reduces secretions (saliva, bronchial) and prevents vagal-induced bradycardia. Adverse Effects A. Ocular • Local irritation, allergic dermatitis (eyelids), papillary conjunctivitis, keratitis • Angle-closure glaucoma risk → rare in normal eyes; IOPelevation unpredictable in open-angle glaucoma • Mydriasis → photophobia, glare B. Systemic • Rapid systemic absorption → dose-dependent toxicity • Peripheral effects (low dose): dry mouth, depressed salivation, facial flushing, inhibited sweating • Central effects (high dose): restlessness, hallucinations, somnolence, convulsions • Children <3 years, Down syndrome, or neurologically impaired → higher sensitivity Systemic Reactions to Atropine in Children: Diffuse cutaneous flush, Depressed salivation/thirst, Fever, Urinary retention, Tachycardia, Somnolence, Excitement/restlessness and hallucinations, Speech disturbances, Ataxia, Convulsion Contraindications • Hypersensitivity to belladonna alkaloids • Open-angle or angle-closure glaucoma • Known IOPelevation tendency • Caution: infants, small children, elderly, Down syndrome Treatment of Overdose • Mainly supportive: hydration, temperature control • Severe/life-threatening: Physostigmine (anticholinesterase) • Adults: 1–2 mg IVslowly, may repeat every 30 min if needed • Children: 0.02 mg/kg IM/slow IV, max 0.5 mg/min, repeat up to 2 mg
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 8 | P a g e drprabhatdevkota@gmail.com High-Yield Exam Pearls • Most potent cycloplegic and mydriatic agent • Mydriasis lasts up to 10 days, cycloplegia 7–12 days • Topical atropine: rapid systemic absorption → caution in children & elderly • Used in latent hyperopia, accommodative esotropia, uveitis, myopia control, and pharmacologic amblyopia therapy • Overdose → CNS effects and death in young children possible • Physostigmine is the antidote for severe toxicity ATOM (Atropine for the Treatment of Myopia) Study Mechanism of Action (MOA) • Atropine → increases retinal dopamine activity (proposed mechanism) • ↓ Axial elongation of the eyeball • ↓ Myopia progression ATOM I (2006) Study Design • 1% atropine vs placebo • Duration: 2 years Key Findings • ↓ Myopia progression (~77% reduction) • ↓ Axial length elongation • Highly effective but associated with significant adverse effects Adverse Effects • Photophobia • Near vision blur (loss of accommodation) • Allergic conjunctivitis/dermatitis (occasionally) Limitation • Marked rebound phenomenon after stopping treatment ATOM II (2012) Study Design • Compared 0.5%, 0.1%, and 0.01% atropine • Duration: 2 years treatment + washout Key Findings • 0.01% atropine had: o Least adverse effects o Least rebound after discontinuation o Better long-term efficacy despite slightly less initial effect
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 9 | P a g e drprabhatdevkota@gmail.com HOMATROPINE Pharmacology • Class: Nonselective muscarinic antagonist (anticholinergic) • Source: Partly synthetic; derived from Solanaceae family (like atropine) • Potency: ~1/10th as potent as atropine • pKa: 9.88 → ~0.32% un-ionized at physiological pH → limited corneal penetration • Stability: Quite stable in solution • Commercial Formulations: Hydrobromide salt, 2% and 5% ophthalmic solution Ocular Pharmacokinetics • Mydriasis: Maximum effect ~40 minutes after 1% solution • Duration: Pupil recovery 1–3 days • Cycloplegia: Less than atropine, more prolonged than cyclopentolate; weak in dark irides Clinical Uses • Anterior uveitis – reduces ciliary spasm, prevents posterior synechiae • Not preferred for: • Cycloplegic refraction (weak cycloplegia) • Fundus examination (prolonged mydriasis in dark irides) Side Effects • Similar to atropine: • Ocular: irritation, allergic reactions, mydriasis, blurred near vision • Systemic (rare with topical use): CNS toxicity, especially in elderly • Toxicity managed like atropine overdose Contraindications • Hypersensitivity to belladonna alkaloids • History of glaucoma (angle-closure or open-angle) • Caution in infants, elderly, and nursing mothers (small amounts excreted in breast milk; considered compatible with breastfeeding) Exam Pearls • Shorter-acting and less potent than atropine → useful when moderate cycloplegia and mydriasis is needed • Preferred over atropine when less systemic toxicity is desired • Weak cycloplegic effect → not suitable for fundus exams or refraction in children • Main use: anterior uveitis management
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 10 | P a g e drprabhatdevkota@gmail.com TROPICAMIDE Class / Pharmacology • Synthetic derivative of tropic acid. • Nonselective muscarinic antagonist; may have moderate M4 receptor selectivity. • pKa: 5.37 → ~2.3% ionized at physiologic pH → high corneal penetration (better than atropine, homatropine, cyclopentolate). • Commercial forms: 0.25%, 0.5%, 1% solutions. • Fast onset and short duration compared with other anticholinergics. MOA: Tropicamide is a short-acting competitive M3 muscarinic antagonist that blocks parasympathetic input to the iris sphincter (→ mydriasis) and ciliary muscle (→ cycloplegia), causing unopposed sympathetic dilation and loss of accommodation. Ocular Pharmacokinetics Parameter Tropicamide Comparison Mydriasis onset 20–40 min Faster than atropine, homatropine, cyclopentolate Max pupil dilation 4 mm (1%) 0.25% sufficient for routine ophthalmoscopy Duration of mydriasis ~6 hours Shorter than other anticholinergics Cycloplegia onset 30 min Dose-dependent; less than mydriasis Residual accommodation (1% tropicamide) <2 D Returns within 6 hours Corneal penetration High Due to low ionization at physiologic pH Prior proparacaine: minimally prolongs mydriasis and cycloplegia; not routinely required. Clinical Uses Mydriasis for fundoscopy / retinal exams: Fast-acting, short duration, suitable for routine ophthalmoscopy. Less affected by iris pigmentation. Cycloplegia (refraction): Short-acting, stabilizes accommodation fluctuations. Effective for distance refraction in school-aged children with low–moderate hyperopia. 1% tropicamide comparable to 1% cyclopentolate for distance refraction.
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 11 | P a g e drprabhatdevkota@gmail.com Combination therapies: 0.25% tropicamide + 1% hydroxyamphetamine (Paremyd) → optimal dilation with minimal cycloplegia. Alternative: 0.5% tropicamide + 2.5% phenylephrine. Research / diagnostic use: Evaluated in early detection ofAlzheimer’s and Parkinson’s via pupillary response (experimental). Side Effects Ocular: Transient stinging on instillation. May increase IOPin open-angle glaucoma; usually small, but can exceed 10 mm Hg in some. Systemic: Rapid absorption but low affinity for systemic muscarinic receptors → systemic reactions rare. Is generally safe in patients with cardiovascular disease or neonates. Rare acute hypersensitivity / syncope reported (mostly children). Contraindications • Hypersensitivity to belladonna alkaloids (cross-reactivity possible). • Narrow anterior chamber angles → risk of angle-closure glaucoma, though low (~0.03–0.3% in screened adults). • Caution in glaucoma patients (recheck IOPpost-dilation). Exam Pearls • Tropicamide has greater mydriatic than cycloplegic effect, fast onset, short duration → drug of choice for routine fundus exams. • Cycloplegia: dose-dependent; short-acting, less suitable for latent hyperopia testing in children. • Paremyd (0.25% tropicamide + 1% hydroxyamphetamine) → clinically useful mydriasis with minimal effect on accommodation. • Safe in cardiovascular disease; rare systemic toxicity. • Useful in school-aged children for distance refraction; faster recovery than cyclopentolate or homatropine.
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 12 | P a g e drprabhatdevkota@gmail.com CYCLOPENTOLATE Pharmacology • Class: Nonselective muscarinic antagonist (anticholinergic, cycloplegic & mydriatic) • Solubility: Water-soluble ester • pKa: 8.4 → mostly ionized at physiologic pH → moderate corneal penetration • Commercial Formulations: 0.5%, 1%, 2% ophthalmic solution MOA: Cyclopentolate is a competitive muscarinic (M3) receptor antagonist that blocks parasympathetic stimulation of the iris sphincter (→ mydriasis) and ciliary muscle (→ cycloplegia), producing strong cycloplegia with intermediate duration. Ocular Pharmacokinetics Parameter Whites Blacks / Dark Irides Mydriasis onset 20–30 min (0.5–1%) 30–60 min (0.5–1%) Cycloplegia onset 30–60 min (0.5–1%) 30–60+ min (1%) Residual accommodation ~0.5–1.25 D 0.83–1.84 D (depends on concentration) Duration of effect Mydriasis & cycloplegia < 24 h Mydriasis & cycloplegia < 24 h Max mydriasis usually ~6.5–7.5 mm in light irides Pupils dilated with cyclopentolate do not constrict to bright light → useful for fundus photography Cycloplegic effect sufficient for routine refraction in infants, children, adults Clinical Uses • Cycloplegic refraction – drug of choice for children and routine refraction • Cycloplegia nearly comparable to atropine in children & adults, but faster onset & shorter duration • Anterior uveitis – alternative to atropine, especially in patients sensitive to atropine • Mydriasis for fundus examination and ophthalmic photography • Not preferred for prolonged cycloplegia (short duration) Side Effects Ocular Transient stinging / irritation (concentration-dependent) Conjunctival hyperemia Allergic blepharoconjunctivitis (rare) Increased intraocular pressure → may precipitate acute glaucoma in narrow angles Systemic / CNS (dose-dependent, more common in children) Drowsiness, ataxia, disorientation
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 13 | P a g e drprabhatdevkota@gmail.com Incoherent speech, restlessness, visual/tactile hallucinations Psychotic reactions (children, 2% solution) Rare: grand mal seizures (especially in neurologically impaired children or with concomitant drugs) Peripheral atropine-like effects (flushing, dry mucous) are rare Contraindications • Infants, young children → avoid >0.5% solution • Children with spastic paralysis or brain damage • Known hypersensitivity to cyclopentolate • Narrow-angle or open-angle glaucoma • Caution: systemic absorption reduced by nasolacrimal occlusion Exam Pearls • Cyclopentolate is first-line for routine cycloplegic refraction in children • Faster onset and shorter duration than atropine → useful for outpatient refractions • Dark irides require higher concentration or repeated doses for adequate cycloplegia • CNS toxicity is dose-dependent; children are more susceptible • Toxicity treatment is same as atropine
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 14 | P a g e drprabhatdevkota@gmail.com MYDRIATICS PHENYLEPHRINE Class: Synthetic sympathomimetic amine (α1-adrenergic agonist) MOA: Stimulates α1 receptors → contracts iris dilator → mydriasis Constricts conjunctival arterioles → blanching of conjunctiva Stimulates Müller’s muscle → widens palpebral fissure Minimal β-receptor effect Minor effect via norepinephrine release from adrenergic nerve terminals IOP Effect: May decrease IOP in normal & open-angle glaucoma eyes Pregnancy Category: C Stability: Oxidizes on exposure to air, light, or heat → antioxidants like sodium bisulfite added Preparations Concentration Common Use 2.5% Routine mydriasis, infants, elderly 10% Breaking posterior synechiae, peripheral vessel vasoconstriction during LASIK, diagnostic in Horner’s syndrome Shelf-life: Sensitive to light, heat, air; store per manufacturer instructions Pharmacokinetics & Mydriasis • Onset: 45–60 min • Duration: 6–7 hours • Effect on accommodation: Minimal (~1–2 D loss vs cycloplegics) • Response influenced by: • Iris color (poorer dilation in dark irides) • Corneal integrity (enhanced after trauma or anesthetic) • Combination with tropicamide → faster, more convenient mydriasis Clinical Uses • Diagnostic Mydriasis – routine fundus exam or photography • Breaking posterior synechiae – typically 10% with topical anesthetic • Peripheral corneal vessel constriction – e.g., during LASIK • Prevention of miotic cysts – with echothiophate therapy in glaucoma or accommodative esotropia • Ptosis management / Horner’s syndrome test – 1% solution for denervation hypersensitivity Side Effects Ocular • Transient stinging, pain, lacrimation
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 15 | P a g e drprabhatdevkota@gmail.com • Keratitis • Pigmented aqueous floaters (age & iris color-dependent, disappear in 12–24 h) • Rebound miosis or conjunctival congestion • Conjunctival hypoxia • Allergic dermatoconjunctivitis (“scalded” appearance) Systemic (more common with 10% or multiple doses) • Hypertension → acute rise in systolic & diastolic BP • Tachycardia or reflex bradycardia • Occipital headache • Ventricular arrhythmias, subarachnoid hemorrhage • Skin blanching • High-risk groups: elderly, neonates, cardiac disease, insulin-dependent diabetes, idiopathic orthostatic hypotension Drug interactions: Avoid with MAO inhibitors, tricyclic antidepressants, reserpine, guanethidine, methyldopa Caution with atropinized patients → enhanced pressor effect Contraindications / Precautions • 10% phenylephrine: use with caution in: • Cardiac disease, hypertension, aneurysms, advanced arteriosclerosis • Infants, elderly → only 2.5% recommended • Single drop per hour per eye; avoid prolonged or repeated use • Avoid in combination with MAO inhibitors, TCA, reserpine, guanethidine, methyldopa • Avoid in patients previously atropinized Exam Pearls • Phenylephrine does not produce significant cycloplegia → mainly mydriatic • 2.5% is routine safe concentration, 10% reserved for specific therapeutic/diagnostic use • Iris color & corneal integrity influence drug efficacy • Useful in Horner’s syndrome diagnosis – 1% phenylephrine shows dilation only in postganglionic lesions • Systemic absorption risks increase with: age extremes, compromised health, high concentration, multiple drops
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 16 | P a g e drprabhatdevkota@gmail.com MIOTICS Pilocarpine Available Concentrations: 0.5%, 1%, 2%, 4%, 6% Drug Class • Direct-acting muscarinic cholinergic agonist (parasympathomimetic) Receptor Action • Stimulates M1, M2, M3, M4, and M5 muscarinic receptors Mechanism ofAction • Iris sphincter contraction → Miosis • Ciliary muscle contraction → Spasm of accommodation • Contraction of longitudinal ciliary muscle → Pulls scleral spur → Opens trabecular meshwork → ↑ Conventional aqueous outflow → ↓ Intraocular pressure (IOP) Pharmacokinetics Parameter Value Onset ~15 minutes Peak effect 30–60 minutes Duration ~4 hours Indications • Primary open-angle glaucoma (POAG) • Acute angle-closure glaucoma (AACG) (after initial IOP reduction) • Secondary glaucoma • Before laser peripheral iridotomy (LPI) • Reversal of pharmacologic mydriasis (occasionally) Adverse Effects Ocular • Miosis • Accommodative spasm • Brow ache/headache • Conjunctival hyperemia • Lid myokymia • Reduced night vision • Retinal detachment (rare; especially in high myopes) Systemic (SLUDGE Syndrome) • S – Salivation • L – Lacrimation • U – Urination • D – Diarrhea • G – Gastrointestinal cramps
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 17 | P a g e drprabhatdevkota@gmail.com • E – Emesis (nausea/vomiting) Additional: • Bradycardia • Hypotension • Bronchospasm • Sweating Contraindications • Significant cataract (especially PSC/NS) • Young patients (<40 years) • Neovascular glaucoma (NVG) • Uveitic glaucoma • High myopia (↑ risk of retinal detachment) • Bronchial asthma/COPD • Hypersensitivity • Caution with succinylcholine anesthesia (prolonged neuromuscular blockade) Pilocarpine Preparation ➢ 0.125% Pilocarpine Preparation • 1 mL of 1% pilocarpine • o 7 mL normal saline/artificial tears • = 8 mL of 0.125% pilocarpine Use • Diagnosis ofAdie's tonic pupil (denervation supersensitivity) ➢ 0.1% Pilocarpine Preparation • 1 mL of 1% pilocarpine • o 9 mL normal saline • = 10 mL of 0.1% pilocarpine Use • Evaluation of anisocoria, particularly when assessing cholinergic supersensitivity.
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 18 | P a g e drprabhatdevkota@gmail.com CORTICOSTEROIDS Mechanism ofAction (MOA) Genomic Action Bind cytoplasmic glucocorticoid receptors Steroid–receptor complex → nucleus → modulates gene transcription ↑ Anti-inflammatory proteins (lipocortin/annexin-1) ↓ Pro-inflammatory genes CoreAnti-inflammatory Effects Inhibit phospholipase A2 → ↓ arachidonic acid → ↓ prostaglandins & leukotrienes ↓ Cytokines (IL-1, IL-2, TNF-α) ↓ Capillary permeability & edema ↓ Leukocyte adhesion & migration Stabilize lysosomal membranes ↓ Fibroblast proliferation & collagen synthesis Exam Pearl: Steroids act upstream of NSAIDs in the arachidonic acid pathway. Indications in Ophthalmology 1. Eyelids Allergic blepharitis Contact dermatitis Herpes zoster dermatoblepharitis Chemical burns Neonatal hemangioma 2.Conjunctiva Allergic conjunctivitis Vernal keratoconjunctivitis Herpes zoster conjunctivitis Chemical burns Mucocutaneous conjunctival lesions 3.Cornea Immune keratoplasty rejection Disciform keratitis Marginal infiltrates Interstitial keratitis Acne rosacea keratitis Chemical burns Avoid in active epithelial HSV keratitis
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 19 | P a g e drprabhatdevkota@gmail.com 4.Uvea Anterior uveitis Posterior uveitis Sympathetic ophthalmia 5.Sclera Scleritis Episcleritis 6.Retina Retinal vasculitis 7.Optic Nerve Optic neuritis Temporal arteritis (systemic steroids emergency) 8.Orbit Orbital pseudotumor Graves’ophthalmopathy 9.Extraocular Muscles Ocular myasthenia gravis
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 20 | P a g e drprabhatdevkota@gmail.com Drug Concentration / Form Key Features / High-Yield Points Prednisolone Acetate 1% (suspension) Most effective for anterior segment inflammation- Acetate > phosphate (better corneal penetration & receptor affinity) No added benefit above 1% Severe inflammation: pulse dosing possible (e.g., every 1 min × 5 min/hour) Gold standard for anterior uveitis Dexamethasone 0.1% (alcohol or phosphate) Alcohol formulation more potent than phosphate Peak aqueous levels at 90–120 min Long intraocular persistence High IOP-elevating potential Fluorometholone (FML) 0.1%–0.25% (suspension) Progesterone analogue Lower risk of IOPrise Alcohol < acetate in potency Used for mild to moderate inflammation Loteprednol Etabonate (LE) 0.2% & 0.5% Soft steroid; rapidly metabolized → lower IOP rise Effective for allergic conjunctivitis, giant papillary conjunctivitis (GPC), postoperative inflammation Less potent than prednisolone acetate in severe uveitis Lower risk of steroid-induced glaucoma Potency Drugs Very High Potency Dexamethasone 0.1%, Betamethasone 0.1% High Potency Prednisolone acetate 1%, Fluorometholone 0.25%–0.5% (suspension) Moderate Potency Rimexolone 1%, Loteprednol etabonate 0.5% Low Potency / Soft Steroids Fluorometholone 0.1% (suspension), Loteprednol etabonate 0.2%, Hydrocortisone 1%
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 21 | P a g e drprabhatdevkota@gmail.com Ocular Side Effects Posterior Subcapsular Cataract (PSC) Dose & duration dependent Risk increases: 15 mg/day systemic prednisone Long-term topical use Children more susceptible Often irreversible Mechanism (theory): Steroid binds lens crystallins → sulfhydryl exposure → protein aggregation Steroid-Induced Glaucoma Onset: 2–8 weeks Reversible after stopping Higher risk: POAG patients First-degree relatives High myopes (>5D) Children Potency for IOPrise: Dexamethasone > Prednisolone > FML ≈ Rimexolone > Loteprednol Mechanism: ↓ Trabecular outflow ↑ Glycosaminoglycans Cytoskeletal changes in trabecular meshwork ↓ Phagocytosis Infection Risk Steroids: Suppress immunity Mask symptoms Never use alone in active infection. High-risk infections: Fungal keratitis HSV epithelial keratitis Bacterial infections (if no scarring risk, avoid) Delayed Corneal Healing ↓ Fibroblast activity ↓ Collagen synthesis Risk of corneal melt Scleral thinning Steroid-induced Uveitis (Rare) More common in blacks
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 22 | P a g e drprabhatdevkota@gmail.com AC cells + flare Stop steroid → improvement Mydriasis & Ptosis Reversible Possibly vehicle-related effect Calcific Band Keratopathy Seen with phosphate formulations Systemic Side Effects (Especially with systemic/periocular use) Head to Toe CNS o Mood changes (euphoria, irritability) o Depression o Steroid psychosis o Insomnia o Pseudotumor cerebri (children) o Seizures (rare) Eye o Posterior subcapsular cataract (PSC) o Steroid-induced glaucoma o Delayed wound healing o Increased risk of infections (HSV, fungal) Cardiovascular o Hypertension o Fluid retention o Edema o Exacerbation of heart failure o Dyslipidemia o Accelerated atherosclerosis (long-term) Respiratory o Increased susceptibility to infections o Reactivation ofTB Gastrointestinal o Gastritis o Peptic ulcer disease o GI bleeding o Pancreatitis (rare) o Hepatic steatosis (long-term)
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 23 | P a g e drprabhatdevkota@gmail.com Hematologic / Immune o Immunosuppression o Masking of infection o Leukocytosis (neutrophilia) o Poor vaccine response Musculoskeletal o Osteoporosis (most important) o Pathological fractures o Avascular necrosis (femoral head) o Proximal myopathy o Growth retardation (children) Endocrine / Metabolic o Cushingoid features (moon face, buffalo hump) o Hyperglycemia / Steroid-induced Diabetes o Adrenal suppression o Growth suppression o Weight gain o Negative nitrogen balance Skin o Skin thinning o Striae o Acne o Easy bruising o Delayed wound healing o Hirsutism Electrolyte / Renal o Sodium retention o Hypokalemia o Fluid retention Reproductive o Menstrual irregularities o Decreased fertility (long-term) Very High-Yield Exam Pearls • Most common serious complication: Osteoporosis • Classic cataract: Posterior subcapsular cataract • Classic glaucoma: Steroid-induced open-angle glaucoma • Abrupt withdrawal →Acute adrenal crisis
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 24 | P a g e drprabhatdevkota@gmail.com • Long-term use → Cushing’s syndrome Contraindications Absolute Active epithelial HSVkeratitis Untreated fungal infection Active TB Relative Glaucoma Diabetes Hypertension CHF Peptic ulcer Osteoporosis Psychosis Drug interactions: MAO inhibitors Phenytoin, barbiturates → increase steroid metabolism Reduce anticoagulant effect Monitoring Protocol Patients on topical steroids: Check IOP every 2–4 weeks Slit lamp for: Dendrites Fungal keratitis PSC Long-term → lens & optic nerve evaluation Systemic therapy: BP Blood glucose Bone density Cataract screening
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 25 | P a g e drprabhatdevkota@gmail.com GENERAL PRINCIPLES OF PREPARATION Reconstitution Converting a dry powder (vial) into a liquid solution by adding sterile water or sterile saline. Example: Amphotericin B 50 mg vial + 10 mL sterile water → 5 mg/mL solution Purpose: To make the drug usable for topical or systemic use Key Points: No change in drug concentration beyond the simple solution Done for injectables or powders Fortification The use of reformulations of parenteral antibiotics as eye drops with non-marketed composition or concentrations. Increasing the concentration of a drug above its standard commercial preparation for severe infections (especially corneal infections). Example: Tobramycin commercial drops 0.3% (3 mg/mL) → fortified to 1.4% (14 mg/mL) using injectable Tobramycin 40 mg/mL Purpose: To achieve higher therapeutic levels in the cornea Key Points: Usually done with injectables, not commercial drops (if concentration needs to increase) Must be prepared aseptically Stored refrigerated at 2–8°C, short shelf-life (≈7 days) STANDARD FORTIFIED PREPARATIONS Drug Final Concentration Source Coverage Cefazolin 50 mg/mL 1 g powder vial Gram + Ceftazidime 50 mg/mL 1 g powder vial Gram – (Pseudomonas) Vancomycin 50 mg/mL (15–25 mg possible) 500 mg vial MRSA, resistant Gram + Tobramycin 14 mg/mL 40 mg/mL injection Gram – Amikacin 20–40 mg/mL IV formulation Nocardia INDICATIONS OF FORTIFIED DROPS • Moderate–to–severe corneal ulcers • Rapidly progressive / fulminant keratitis • Large or visually significant infiltrates • Presence of hypopyon • Eyes unresponsive to initial therapy • Fluoroquinolone-resistant infections (e.g., MRSA, resistant pseudomonas)
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 26 | P a g e drprabhatdevkota@gmail.com • Post-trabeculectomy blebitis • Endophthalmitis • Pediatric ocular infections (higher bacterial frequency) • When higher drug concentration is required Preparation & Handling • Organism-directed selection is essential. • Prepare under strict aseptic conditions (preferably laminar airflow). • Compounded by a doctor/pharmacist using a sterile disposable syringe. • Label preparation & expiry dates clearly. • Educate patient regarding dose and storage. • Shake before instillation. Storage & Stability (MCQ Favourite) • Store at 2–8°C (≈4°C). • Preservative-free → short shelf life. • Discard after 7 days. • Minimize contamination with proper handling. Advantages • Achieve high stromal drug levels. • Provide bactericidal concentrations. • Particularly effective in deep or severe ulcers. Limitations • Ocular surface / epithelial toxicity possible. • Require frequent dosing. • Dependence on refrigeration. • Limited shelf life. • Epithelial toxicity. • Aminoglycosides & vancomycin → delayed epithelial healing. • Causes retarded corneal re-epithelialization
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 27 | P a g e drprabhatdevkota@gmail.com Common Topical Preparations Cefazolin 50 mg/mL (5%) --------same for Ceftazidime 50 mg/mL (5%) Preparation • 500 mg Cefazolin powder + 10 mL sterile distilled water (DW) = 50 mg/mL (5%) OR • 250 mg Cefazolin powder + 5 mL sterile distilled water (DW) = 50 mg/mL (5%) Store at 4°C, protect from light, use within 7 days Vancomycin 15,25,50 mg/mL (1.5%,2.5%,,5%) Method: To a 500 mg vial of vancomycin Add 33 ml of 0.9% sodium chloride (no preservatives) to produce a solution of 15 mg/ml. Add 20 ml of 0.9% sodium chloride (no preservatives) to produce a solution of 25 mg/ml. Add 10 ml of 0.9% sodium chloride (no preservatives) to produce a solution of 50 mg/ml. Storage: Refrigerate and shake well before instillation. Tobramycin 14 mg/mL (1.4%) ----------- same for Gentamicin 14 mg/mL (1.4%) Preparation • Gentamicin/Tobramycin eye drops 0.3% (3 mg/mL) = 5 mL o Drug content = 3 × 5 = 15 mg • Add Gentamicin/Tobramycin injection (40 mg/mL) = 2 mL o Drug content = 40 × 2 = 80 mg Calculation • Total drug = 15 + 80 = 95 mg • Total volume = 5 + 2 = 7 mL • Final concentration = 95 ÷ 7 = 13.5 mg/mL • ≈ 1.35% (commonly referred to as 1.4% or 14 mg/mL) Amikacin 40 mg/mL (4%) Amikacin vial 100 mg powder To obtain 40 mg/mL: Add 2.5 mL sterile water for injection Especially effective for: Nocardia keratitis Amphotericin B 0.15% Reconstitute 50 mg vial of amphotericin B powder with 10 mL sterile water→ 5 mg/mL Take 3 mL of 5 mg/mL solution Add 7 mL sterile water / NS Final volume = 10 mL Final concentration = 1.5 mg/mL (0.15%) Store at 4°C, protect from light, use within 7 days
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 28 | P a g e drprabhatdevkota@gmail.com Voriconazole (1%) Take Voriconazole powder 200 mg Reconstitute with 19 mLsterile water for injection Final volume → 20 mL Final concentration → 10 mg/mL (≈1%) Storage: Refrigerate at 4°C and shake well before instillation Common Intravitreal Drugs Drug Final Intravitreal Dose Reconstitution & Dilution Injection Volume Vancomycin 1 mg / 0.1 mL • 500 mg vial + 10 mL NS → 50 mg/mL • Take 0.2 mL + 0.8 mL NS → 10 mg/mL 0.1 mL = 1 mg Ceftazidime 2.25 mg / 0.1 mL • 500 mg vial + 2 mL NS → 250 mg/mL • Take 0.1 mL + 0.9 mL NS → 25 mg/mL 0.1 mL = 2.5 mg (≈2.25 mg clinically accepted) Dexamethasone 400 µg / 0.1 mL Commercial preparation 4 mg/mL Withdraw 0.1 mL directly (= 0.4 mg = 400 µg) Amphotericin B 5 µg / 0.1 mL • 50 mg vial + 10 mL D5W → 5 mg/mL • Take 0.1 mL + 9.9 mL D5W → 50 µg/mL 0.1 mL = 5 µg
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 29 | P a g e drprabhatdevkota@gmail.com ANTIBACTERIAL AGENTS Bactericidal Bacteriostatic @csmt Penicillins Macrolides Cephalosporins Tetracyclines Aminoglycosides Chloramphenicol Fluoroquinolones Sulfonamides Vancomycin Classification ofAntibiotics A. Inhibitors of Cell Wall Synthesis β-lactams Penicillins Cephalosporins Glycopeptides – Vancomycin Bacitracin B. Inhibitors of Protein Synthesis ➤ 30S Ribosomal Subunit Aminoglycosides (Gentamicin, Amikacin) Tetracyclines (Doxycycline) ➤ 50S Ribosomal Subunit Chloramphenicol Macrolides (Azithromycin, Erythromycin) C. Inhibitors of Nucleic Acid Synthesis Fluoroquinolones (Ciprofloxacin, Moxifloxacin) D.Antimetabolites (Folate Pathway Inhibitors) Sulfonamides Trimethoprim Cotrimoxazole Gram-positive Gram-negative Cefazolin 50 mg/mL Tobramycin 3–14 mg/mL Chloramphenicol 5–10 mg/mL Gentamicin 3–14 mg/mL Moxifloxacin 0.5% Amikacin 20 mg/0.5 mL Vancomycin 15–50 mg/mL Ceftazidime 50 mg/mL Ciprofloxacin 3 mg/mL Levofloxacin 3 mg/mL Ofloxacin 3 mg/mL
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 30 | P a g e drprabhatdevkota@gmail.com A. Beta-Lactams: Inhibit bacterial cell wall peptidoglycan synthesis → bactericidal Cephalosporins 1st Gen: Cephalexin, Cephradine, Cefadroxil, Cefazolin 2nd Gen: Cefaclor, Cefprozil, Cefuroxime, Cefoxitin, Cefotetan 3rd Gen: Cefixime, Cefdinir, Cefotaxime, Ceftriaxone, Ceftazidime 4th Gen: Cefepime 5th Gen: Ceftaroline, Ceftobiprole Mechanism ofAction (MOA) Bactericidal β-lactam antibiotics Inhibit bacterial cell wall synthesis Bind penicillin-binding proteins (PBPs) → prevent peptidoglycan cross-linking → weak cell wall → bacterial lysis Spectrum ofActivity: Active mainly against GPC and GNB • Cefazolin (1G) Fortified 5% topical Gram-Positive: MSSA (Methicillin-sensitive Staph aureus), Streptococcus spp. (S. pyogenes, S. pneumoniae – penicillin-sensitive) Gram-Negative: Limited/modest • Ceftazidime (3G) Intravitreal 2.25 mg/0.1 mL Gram-Negative: Pseudomonas aeruginosa, Moderate coverage of Enterobacteriaceae Gram-Positive: Limited/reduced activity Indications • Bacterial Corneal Ulcers • Gonococcal Ophthalmia Neonatorum • Preseptal Or Orbital Cellulitis • Bacterial Endophthalmitis Adverse Effects Ocular ADRs: Rare; mild irritation Systemic ADRs: Hypersensitivity: rash, urticaria, fever, bronchospasm, anaphylaxis GI upset: nausea, vomiting, diarrhea C. difficile colitis Joint/skin reactions Renal impairment Vitamin K deficiency → bleeding Contraindications Known cephalosporin allergy or penicillin allergy Hemophilia
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 31 | P a g e drprabhatdevkota@gmail.com B. Glycopeptides Vancomycin 50 mg/mL eye drops (fortified) / Intravitreal solution Mechanism ofAction (MOA) Bactericidal Inhibits bacterial cell wall synthesis Binds to D-Ala-D-Ala terminus of peptidoglycan precursors→ Prevents cross-linking of peptidoglycan → weak cell wall → bacterial lysis Spectrum ofActivity Gram-Positive: Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Streptococcus pneumoniae, Enterococcus spp. (Highly active against Gram-positive bacteria, including MRSA and penicillin-resistant S. pneumoniae) Anaerobes: Clostridium difficile Not active against Gram-negative bacteria Indications • Bacterial Endophthalmitis • Ocular infections caused by MRSA or penicillin-resistant streptococci • Moderate to severe Preseptal Cellulitis (systemic use) • Serious infections when other antibiotics fail Adverse Effects Ocular ADRs (topical/intravitreal) Irritation, burning, stinging (especially if not buffered) Rare corneal epithelial toxicity at high concentrations Systemic ADRs (IV/oral) Nephrotoxicity Ototoxicity → hearing loss, tinnitus, vertigo “Red man syndrome” (rapid infusion) → flushing, hypotension Rare hematologic effects: neutropenia, thrombocytopenia Contraindications • Known hypersensitivity or allergy • Caution in patients with renal impairment, hearing disorders, or concurrent ototoxic/nephrotoxic drugs
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 32 | P a g e drprabhatdevkota@gmail.com Bacitracin: Polypeptide antibiotic, Topical ointment (usually 500 units/g) Mechanism ofAction (MOA) Inhibits bacterial cell wall synthesis by blocking dephosphorylation of bactoprenol Bactericidal against Gram-positive bacteria Spectrum ofActivity Gram-Positive: Staphylococcus aureus (including some MRSA), Streptococcus spp, Corynebacteria Gram-Negative: Minimal / negligible activity Ocular Indications • Superficial bacterial conjunctivitis (mild cases) • Blepharitis (Staph-related) • Prophylaxis after minor ocular trauma or suture sites • Often used in combination with neomycin or polymyxin B Adverse Effects • Ocular irritation, itching, burning • Rare hypersensitivity reactions
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 33 | P a g e drprabhatdevkota@gmail.com C.Aminoglycosides Gentamicin 0.3% eye drops / 0.3% ointment Tobramycin 0.3% eye drops / 0.3% ointment Neomycin 0.5%–1% ophthalmic ointment Amikacin (used intravitreally / fortified for corneal ulcers) Mechanism ofAction (MOA) • Bactericidal → inhibits protein synthesis • Binds to 30S ribosomal subunit • Causes misreading of mRNA → defective proteins → bacterial death • Synergistic effect with β-lactams or vancomycin against gram-positive and gram-negative bacteria Spectrum ofActivity Gram-Positive: Staphylococcus aureus, Streptococci & Enterococci Gram-Negative: Pseudomonas aeruginosa, E. coli, Klebsiella, Proteus, Enterobacter, Serratia Indications • Bacterial conjunctivitis • Blepharitis • Keratoconjunctivitis / Corneal ulcers (fortified drops) • Empiric therapy for Pseudomonas corneal ulcers (gentamicin or tobramycin + cefazolin) • Endophthalmitis (amikacin intravitreal for gram-negative coverage) Adverse Effects Ocular ADRs • Punctate epithelial erosions / corneal toxicity • Delayed epithelial healing • Conjunctival hyperemia, chemosis • Rare allergic reactions (cross-reactivity with neomycin ~50%) Systemic ADRs • Nephrotoxicity • Ototoxicity • Pseudotumor cerebri • Retinal damage after intravitreal gentamicin (macular infarction) Contraindications • Hypersensitivity • Use caution in renal impairment (systemic use)
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 34 | P a g e drprabhatdevkota@gmail.com D. Tetracyclines Tetracycline 1% ophthalmic ointment, Doxycycline 100 mg oral Mechanism of Action (MOA) • Bacteriostatic • Binds to 30S ribosomal subunit → Blocks attachment of aminoacyl-tRNA to A site → Inhibits addition of amino acids → ↓ protein synthesis • Inhibits bacterial lipase production → ↓ free fatty acids in meibomian glands • Inhibits matrix metalloproteinases (MMPs) → ↓ corneal collagenase activity • Anti-inflammatory effect (↓ IL-1, TNF-α mediated damage) • Anti-collagenolytic → prevents corneal melting Spectrum of Activity Gram-Positive: Staphylococcus, Streptococcus Gram-Negative: H. influenzae, Vibrio cholerae, Brucella, Yersinia pestis Atypical: Chlamydia (Drug of choice), Rickettsia (DOC) Mycoplasma pneumoniae), Borrelia (Lyme disease) Indications Ocular Infectious • Trachoma • Chlamydial Inclusion conjunctivitis • gonococcal ophthalmia neonatorum (Prophylaxis) Ocular Non-Infectious • Meibomianitis / MGD • Acne rosacea • Recurrent chalazion • Phlyctenular keratoconjunctivitis • Corneal melting / sterile corneal ulcer • Persistent epithelial defects/ chemical injury Adverse Effects Ocular ADRs: Mild irritation / burning, Hypersensitivity reactions Systemic ADRs GI Effect: • Nausea, vomiting, • Diarrhea, • Esophagitis (especially doxycycline) Photosensitivity Teeth & Bone Effects: Tooth discoloration (yellow-brown), Enamel hypoplasia, Bone growth suppression Intracranial Hypertension & Papilledema Contraindications • Hypersensitivity • Pregnancy (2nd & 3rd T)
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 35 | P a g e drprabhatdevkota@gmail.com • Lactating • Children < 8 years (tooth discoloration) • Severe hepatic dysfunction • Caution in renal impairment Polymyxin B 0.1% (Polymyxins, Cationic polypeptide antibiotic) Mechanism ofAction (MOA): Bactericidal → disrupts bacterial cell membrane integrity Cationic detergent → binds phospholipids in Gram-negative bacterial membranes → Increases membrane permeability → osmotic imbalance → cell death Spectrum ofActivity: Gram-negative: P. aeruginosa, E. coli, Klebsiella, Proteus Indications: • External ocular infections (conjunctivitis, blepharitis) • Prevent infection in corneal or conjunctival compromise • Used in combination with other antibiotics or steroids for lid/conjunctival infections • Topical prophylaxis with steroid therapy Adverse Effects: Ocular ADRs: Mild irritation, conjunctival hyperemia, allergic reactions of eyelid/conjunctiva Subconjunctival injection: Pain, chemosis, tissue necrosis Systemic ADRs: Rare with topical use; systemic use is neurotoxic and nephrotoxic Contraindications: Hypersensitivity or intolerance to Polymyxin B
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 36 | P a g e drprabhatdevkota@gmail.com E. Macrolides Erythromycin 0.5%–1% ophthalmic ointment Azithromycin 1% eye drops Mechanism ofAction (MOA) Bacteriostatic → inhibits bacterial protein synthesis • Binds to 50S ribosomal subunit • Prevents elongation of the peptide chain → blocks protein synthesis Reduces Staphylococcus aureus colonization on eyelid margins •Anti-inflammatory effect is secondary to reduction of bacterial load and exotoxin production Spectrum ofActivity Gram-Positive: Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus aureus (except some MRSA) Gram-Negative : H. influenzae, Moraxella catarrhalis, Chlamydia trachomatis / C. pneumoniae, Mycoplasma pneumoniae, Borrelia burgdorferi Indications • Staphylococcal eyelid infections → erythromycin ointment • Prophylaxis of ophthalmia neonatorum → erythromycin ointment • Chlamydial conjunctivitis / Trachoma → oral erythromycin or azithromycin (single 1-g dose in adults, 20 mg/kg in children) Adverse Effects Ocular ADRs • Mild irritation with topical erythromycin or azithromycin drops Systemic ADRs • Gastrointestinal: nausea, vomiting, diarrhea, abdominal pain (most common) • Headache, dizziness, dyspepsia • Mild allergic reactions: urticaria, rashes, fever, eosinophilia Contraindications • Known hypersensitivity • Clarithromycin: avoid in pregnancy unless no alternative therapy
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 37 | P a g e drprabhatdevkota@gmail.com F. Chloramphenicol 0.5% eye drops, 1% ointment Mechanism ofAction (MOA) Bacteriostatic Binds to 50S ribosomal subunit Inhibits peptidyl transferase enzyme Blocks aminoacyl-tRNA binding Prevents peptide bond formation → inhibits bacterial protein synthesis Spectrum ofActivity Gram-Positive: Streptococcus, Staphylococcus Gram-Negative: H. influenzae, Neisseria, Enterobacteriaceae Atypical Organisms: Rickettsia, Chlamydia, Mycoplasma, Spirochetes Indications: Bacterial conjunctivitis Blepharitis External ocular infections Alternative when other antibiotics fail Adverse Effects Ocular ADRs: Mild burning / stinging Ocular irritation Allergic conjunctivitis Eyelid edema (rare) Systemic ADR: Bone marrow suppression: Anemia, leukopenia, thrombocytopenia Idiosyncratic aplastic anemia Hypersensitivity reactions Contact dermatitis Contraindications h/o Hypersensitivity Previous bone marrow suppression / blood dyscrasias h/o aplastic anemia Pre-existing hematologic disorders Neonates (risk of systemic absorption → Gray baby syndrome)
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 38 | P a g e drprabhatdevkota@gmail.com G. Fluoroquinolones Generations: 1st: Nalidixic acid 2nd: Ciprofloxacin, Ofloxacin 3rd: Levofloxacin 4th: Moxifloxacin, Gatifloxacin (C8-methoxy, dual target → lower resistance) Mechanism ofAction (MOA) Rapidly inhibit bacterial DNAsynthesis → bactericidal Target enzymes: DNAgyrase (Topoisomerase II) → mainly in Gram-negative bacteria Topoisomerase IV → mainly in Gram-positive bacteria These enzymes maintain supercoiling and separation of DNAduring replication Human cells lack these enzymes → selective toxicity Spectrum ofActivity Gram-Negative: Enterobacteriaceae, Haemophilus influenzae, Neisseria, Pseudomonas (especially ciprofloxacin) Gram-Positive: Staphylococcus aureus, Coagulase-negative Staph, Streptococcus (better with 3rd & 4th gen) Why 4th Generation is Superior? C8-methoxy group Dual enzyme inhibition Requires 2 mutations for resistance Enhanced Gram-positive activity Maintains Gram-negative potency Side Effects Burning/stinging Bitter taste Conjunctival hyperemia Foreign body sensation Ciprofloxacin-Specific: White corneal precipitates Bandage contact lens deposits Mild epithelial cytotoxicity (minimal clinically) Pediatric use: Avoid <2 years
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 39 | P a g e drprabhatdevkota@gmail.com ANTIFUNGAL AGENTS Indications Filamentous fungi (Aspergillus, Fusarium): Natamycin 5% (drug of choice), Amphotericin B 0.15– 0.3%, Voriconazole 1% Yeast (Candida): Amphotericin B (drug of choice), Nystatin 3.5% ointment Systemic therapy: Deep stromal infection, scleral involvement, endophthalmitis, large ulcer >6 mm, immunocompromised patients Topical steroids: Contraindicated during active fungal keratitis Class Subclass / Examples Mechanism of Action Key Notes / PG Pearls Polyenes Large polyenes: Amphotericin B, Nystatin Small polyenes: Natamycin Bind to ergosterol in fungal cell membrane → increase permeability → cell lysis Large polyenes: form pores, concentration- dependent Small polyenes: form blisters, all-or-none, not concentration- dependent Amphotericin B: Drug of choice for Candida keratitis Natamycin: Drug of choice for filamentous fungi (Fusarium, Aspergillus) Azoles Imidazoles: Clotrimazole, Miconazole, Ketoconazole Triazoles: Fluconazole, Itraconazole, Voriconazole Inhibit ergosterol synthesis at low concentration; direct membrane damage at high concentration Voriconazole: Broadest spectrum; first choice in resistant filamentous keratitis Fluconazole: Mainly Candida keratitis Pyrimidines Flucytosine Converted to 5-FU analog → inhibits fungal DNA& RNA synthesis Never used alone; resistance develops rapidly; synergistic with amphotericin B or azoles Echinocandins Micafungin (topical 0.2%) Inhibit 1,3-β-D- glucan synthase → disrupt cell wall → lysis Used in refractory keratitis
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 40 | P a g e drprabhatdevkota@gmail.com Routes ofAdministration Topical: Used for superficial keratitis Dosing: Every 30 min – 1 hourly for the first 24–48 hours, then taper gradually according to clinical response Intracameral / Intrastromal: Voriconazole used for deep stromal infections or anterior chamber involvement Useful in recalcitrant or deep-seated keratitis Systemic (oral): Fluconazole, Ketoconazole, Voriconazole Indicated for deeper ulcers, scleral involvement, post-keratoplasty infections, or immunocompromised patients Monitor liver function tests for systemic azoles Natamycin Class: Polyene (small polyene / tetraene) Mechanism ofAction: Binds ergosterol in fungal cell membrane → forms “blisters” → cell lysis All-or-none action, not concentration-dependent Spectrum: Primarily filamentous fungi: Fusarium >Aspergillus Limited activity against yeast (Candida) Dose / Route: Topical 5% suspension Hourly for first 48–72 hours → taper 3–6 weeks depending on response Adverse Effects / Toxicity: • Corneal/conjunctival hyperemia, epithelial defects • Formation of chalky white deposits on cornea → may obscure monitoring • Rarely systemic effects (minimal absorption) Key Pearls: • Drug of choice for Fusarium keratitis • Surface debridement increases penetration • Least toxic and most stable polyene Amphotericin B Class: Polyene (large polyene) Mechanism ofAction: Binds ergosterol → forms pores → ions leak → osmotic imbalance → cell death Concentration-dependent; pore formation affected by osmotic environment Spectrum: • Candida (first-line) • Moderate activity against Aspergillus and other filamentous fungi • Limited against Fusarium
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 41 | P a g e drprabhatdevkota@gmail.com Dose / Route: Topical 0.15% (freshly prepared in dextrose, stored in dark bottles) Intracameral: 500 µg/0.1 mL Intravitreal: 5 µg/0.1 mL Adverse Effects / Toxicity: Local: punctate epithelial erosions, green conjunctiva, conjunctival nodules Extremely toxic subconjunctivally at higher doses Systemic toxicity if given IV: nephrotoxicity, electrolyte imbalance Key Pearls: Drug of choice for Candida keratitis Penetration improves with debridement Fresh preparation required; turns milky if degraded → discard Itraconazole Class: Triazole Mechanism ofAction: Inhibits 14α-demethylase → blocks ergosterol synthesis → membrane dysfunction Fungistatic at normal doses; some fungicidal activity at higher concentrations Spectrum: • Candida species (yeast) • Limited activity against filamentous fungi (less effective for Fusarium) Dose / Route: Oral 200 mg twice daily (BD) Topical 1% (limited ocular penetration) Adverse Effects / Toxicity: • GI upset, nausea, diarrhea • Hypokalemia, hypertriglyceridemia • Hepatotoxicity (monitor LFTs if long-term) Key Pearls: • Adjunctive agent for fungal keratitis, particularly deeper or refractory Candida infections • Poor corneal penetration limits monotherapy in stromal keratitis Voriconazole Class: Triazole (second-generation, synthetic) Mechanism ofAction: Inhibits 14α-demethylase → prevents ergosterol synthesis → cell membrane dysfunction High potency; lower minimal inhibitory concentration (MIC) than other azoles Spectrum: • Broad-spectrum: Candida, Aspergillus, Fusarium (variable; Fusarium less predictable) • Effective in recalcitrant fungal keratitis and deep stromal infections Dose / Route: Topical 1% (prepared in pharmacy, not commercially available)
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 42 | P a g e drprabhatdevkota@gmail.com Oral 200 mg BD Intrastromal / intracameral / intravitreal injections for deep or anterior chamber involvement Adverse Effects / Toxicity: Systemic: minimal but may cause visual disturbances, mild hepatotoxicity Topical/intrastromal: local irritation Key Pearls: Drug of choice forAspergillus keratitis resistant to natamycin Can be used intrastromally in deep stromal infections or intravitreally in endophthalmitis Cost and availability may limit routine use Fluconazole Class: Triazole Mechanism ofAction: Inhibits 14α-demethylase → blocks ergosterol synthesis → membrane dysfunction Spectrum: • Candida species (yeast) • Limited activity against filamentous fungi (Aspergillus) Dose / Route: Topical 0.2% solution Oral 200 mg/day (deep ulcers, systemic therapy) Adverse Effects / Toxicity: Hepatotoxicity, rash, nausea, headache Rare: Stevens-Johnson syndrome, thrombocytopenia Key Pearls: • Good ocular penetration → suitable for deeper ulcers or systemic therapy • Mainly used for Candida keratitis Exam Pearls • Natamycin 5% = drug of choice for Fusarium keratitis • Amphotericin B = drug of choice for Candida keratitis • Voriconazole = newer azole, effective forAspergillus, Fusarium; use topically, intrastromal, or orally • Flucytosine = never use alone; synergistic with amphotericin B/azoles • Systemic antifungal indications: large/deep ulcer, scleral involvement, endophthalmitis, post- keratoplasty, immunocompromised • Topical steroids = strictly contraindicated in active fungal corneal ulcer • Debridement = increases penetration of Natamycin &Amphotericin B • Polyenes vsAzoles: Polyenes = fungicidal; Azoles = fungistatic at low doses, fungicidal at high doses • Preparation caution: Amphotericin B must be freshly prepared, stored in dark bottles at 2–8°C • Polyenes: Bind ergosterol → pores/blisters → cell lysis • Azoles: Inhibit 14α-demethylase → block ergosterol synthesis → membrane dysfunction
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 43 | P a g e drprabhatdevkota@gmail.com • Flucytosine: Antimetabolite → DNA/RNA synthesis inhibition • Echinocandins: Inhibit glucan synthesis → cell wall lysis Class Drug Mechanism ofAction Dose Side Effects Remarks Polyenes Natamycin Binds ergosterol → membrane “blisters” → cell lysis (all- or-none) Topical 5% suspension hourly → taper 3–6 wks Hyperemia, epithelial defects, chalky deposits Drug of choice for filamentous fungi (Fusarium); surface debridement ↑ penetration; least toxic polyene Amphoterici n B Binds ergosterol → pore formation → cell lysis (concentratio n-dependent) Topical 0.15%; Intracamer al 500 µg/0.1 mL; Intravitreal 5 µg/0.1 mL Punctate epithelial erosions, green conjunctiva; local toxicity Drug of choice for Candida keratitis; freshly prepared, stored in dark bottles; moderate activity against Aspergillus Nystatin Binds ergosterol → pore formation Topical ointment Corneal irritation Poor ocular penetration; rarely used Imidazole s Clotrimazole Inhibits ergosterol synthesis at low dose; direct membrane damage at high dose Topical 1%; Oral 60–150 mg/kg/day Anorexia, nausea, hallucinations, liver enzyme elevation Topical: effective against Aspergillus; systemic toxicity limits routine use Miconazole Inhibits ergosterol synthesis; lysosomal disruption Topical 1% / 10 mg/mL; 2% ointment Surface toxicity on prolonged use Broad-spectrum; stable in solution Ketoconazole Inhibits ergosterol synthesis; high doses Topical 1– 5%; Oral 200–400 mg/day Hepatotoxicity, nausea, gynecomastia Monitor LFTs every 2 weeks on oral therapy
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 44 | P a g e drprabhatdevkota@gmail.com Class Drug Mechanism ofAction Dose Side Effects Remarks disrupt membranes Triazoles Fluconazole Inhibits 14α- demethylase → blocks ergosterol synthesis Topical 0.2%; Oral 200 mg/day Hepatotoxicity, rash, thrombocytopeni a, SJS Good ocular penetration; systemic for deep ulcers; mainly Candida keratitis Itraconazole Inhibits ergosterol synthesis Oral 200 mg BD GI upset, hypokalemia, hypertriglyceride mia Limited corneal penetration; adjunctive therapy Voriconazole Inhibits 14α- demethylase → blocks ergosterol synthesis Topical 1%; Oral 200 mg BD Minimal systemic; visual disturbances Effective for Aspergillus and resistant Fusarium; intrastromal/intraca meral for deep infection; costly Posaconazole Inhibits ergosterol synthesis Oral / Topical Minimal toxicity Emerging therapy for refractory Fusarium keratitis Pyrimidin es Flucytosine Converted to 5-FU → inhibits fungal DNA/RNA synthesis Topical 2%; Oral 50–150 mg/kg/day BD Bone marrow suppression, GI upset Never used alone; synergistic with amphotericin B/azoles Echinocan dins Micafungin Inhibits 1,3- β-D-glucan synthesis → cell wall lysis Topical 0.2% Local irritation Used for refractory keratitis not responding to standard therapy
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 45 | P a g e drprabhatdevkota@gmail.com ANTIVIRAL AGENTS 1. Idoxuridine (IDU) Class: Thymidine nucleoside analog Route: Topical (0.1% solution, 0.5% ointment) Mechanism: Inhibits viral DNAsynthesis Notes: First topically effective antiviral Rarely used today due to: Frequent application requirement Toxicity Availability of newer agents 2.Vidarabine (Ara-A) Class: Adenine nucleoside analog Route: Topical (3% ointment), IV (systemic) Mechanism: Inhibits viral DNApolymerase → blocks viral DNAsynthesis Notes: Water-insoluble Effective for herpetic keratitis Rarely used systemically now 3.Trifluridine Class: Fluorinated thymidine analog Route: Topical 1% solution Mechanism: Inhibits viral thymidylate synthase → blocks viral DNAsynthesis Notes: Not used systemically (rapid degradation in blood) Can be used 2-hourly while awake in active keratitis Useful in dendritic keratitis 4.Acyclovir (ACV) Class: Synthetic guanine nucleoside analog (purine analogue) Routes & Dosage: Topical: 3% ointment, 5×/day for 7–14 days (dendritic keratitis) Oral: 200–800 mg 5×/day for 7–10 days (HSVkeratitis, HZO) Prophylaxis: 400 mg 2×/day (prevent recurrent HSV) IV: 5–10 mg/kg q8h (severe systemic HSV/VZV) Mechanism ofAction: • Guanine analogue is phosphorylated by viral thymidine kinase → forms monophosphate • Monophosphate is further converted by host kinases to triphosphate
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 46 | P a g e drprabhatdevkota@gmail.com • Triphosphate inhibits viral DNApolymerase and incorporates into viral DNA, causing premature DNAchain termination • Selectively active in virus-infected cells → minimal effect on host DNA Spectrum ofActivity: • HSV-1, HSV-2 (primary targets) • VZV (varicella-zoster virus) • EBV (limited) • CMV (only at high IVdoses) Ocular Uses: • Dendritic keratitis: Topical ACV 3% ointment 5×/day × 7–14 days • Stromal keratitis / systemic involvement: Oral ACV 400 mg 5×/day • Prevention of recurrence: Oral ACV 400 mg 2×/day post-surgery or recurrent HSV Adverse Effects (ADR): Topical: Minimal local irritation, stinging, punctate keratitis Oral/IV: Nausea, vomiting, diarrhea, headache, fatigue, dizziness, rash Rare: Nephrotoxicity (IV), neurotoxicity (high IV doses), hematologic abnormalities Contraindication: Hypersensitivity High-Yield Exam Pearls: • Activated only in virus-infected cells → selective toxicity • Topical ACV preferred for superficial dendritic keratitis • Oral ACV used for stromal keratitis, HZO, prophylaxis • Early initiation (<72h) crucial for HZO to prevent keratitis, uveitis, ARN • Resistance rare (<1% immunocompetent, 3–4% immunocompromised) 5.Valacyclovir (VACV) Class: Prodrug of acyclovir (L-valyl ester) → improved oral bioavailability Dose / Route: Acute HSV keratitis / HZO: 1000 mg TID × 7 days Prophylaxis / recurrent HSV: 500–1000 mg once daily Mechanism ofAction (MOA): Hydrolyzed to acyclovir in liver & GI tract Inhibits viral DNApolymerase → blocks viral replication Same spectrum as acyclovir: HSV-1, HSV-2, VZV Ocular Uses / Indication: • HSV keratitis (especially stromal or systemic therapy) • Herpes zoster ophthalmicus (HZO) • Suppression / prophylaxis of recurrent HSV keratitis Adverse Effects (ADR): Headache, nausea, vomiting, diarrhea, fatigue Rare: thrombotic microangiopathy, renal impairment (especially in dehydration) Contraindication: Hypersensitivity to acyclovir or valacyclovir High-Yield Exam Pearls / Remarks:
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 47 | P a g e drprabhatdevkota@gmail.com • Higher oral bioavailability (~55%) vs acyclovir (~10–20%) → better systemic therapy • Convenient dosing → improved compliance • Equivalent efficacy to acyclovir • Useful in immunocompromised and elderly patients (dose adjustment in renal impairment) • Preferred over oral ACV for systemic therapy and prophylaxis 6. Famciclovir Class: Prodrug of penciclovir (guanine analogue) Dose / Route: Oral: 250–500 mg 2–3× daily (HSV, HZO) Mechanism ofAction (MOA): Converted to penciclovir → inhibits viral DNApolymerase → blocks viral replication Long intracellular half-life → less frequent dosing Ocular Uses / Indication: • Herpes zoster ophthalmicus (ophthalmic & systemic) • Suppression of recurrent genital HSV Adverse Effects (ADR): Headache, nausea, GI upset, fatigue Rare: paresthesia, rash Contraindication: Hypersensitivity to famciclovir or penciclovir High-Yield Exam Pearls / Remarks: • Comparable efficacy to acyclovir & valacyclovir for HZO • Significantly reduces duration of postherpetic neuralgia • Well tolerated in immunocompetent and immunocompromised patients • Long half-life allows convenient dosing High-Yield Exam Pearls • Idoxuridine: historical first; rarely used now • Trifluridine: topical only, 1% solution, 2-hourly dosing • Acyclovir: topical 3% ointment or systemic; activates via viral thymidine kinase • Valacyclovir: prodrug of acyclovir; less frequent dosing • HEDS: steroids + antiviral for stromal keratitis; oral acyclovir not effective alone • HZO: oral acyclovir mainstay; topical antivirals useless • Dendritic keratitis: topical antivirals ± debridement Drug MOA Indication + Contraindication Key Points / Pearls Side Effects Idoxuridine – Topical Thymidine analogue → inhibits viral DNA synthesis Superficial HSV keratitis; contraindicated in hypersensitivity Poor bioavailability, toxic, largely obsolete Corneal toxicity, irritation
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 48 | P a g e drprabhatdevkota@gmail.com Drug MOA Indication + Contraindication Key Points / Pearls Side Effects Vidarabine – Topical (compounded) Nucleoside analogue → inhibits viral DNA polymerase HSV keratitis resistant to idoxuridine; hypersensitivity Discontinued commercially; alternative when trifluridine fails Mild ocular irritation Trifluridine – Topical 1% drops Inhibits thymidine synthetase → DNA synthesis in virus & host cells Primary & recurrent HSV-1 & HSV-2 keratitis, dendritic/geographic ulcers; contraindicated in hypersensitivity Drug of choice topical HSV; faster healing than idoxuridine/vidarab ine Burning, stinging, punctate keratopathy, chemosis, impaired wound healing Acyclovir – Topical 3% ointment / Oral / IV Guanine analogue → inhibits viral DNA polymerase → chain termination HSV keratitis, recurrent HSV, HZO, prophylaxis post-surgery; contraindicated in hypersensitivity to acyclovir/valacyclo vir Highly selective; start HZO within 72h; oral prophylaxis reduces recurrences Topical: punctate keratitis; Oral: GI upset, renal, CNS effects Valacyclovir – Oral Prodrug of acyclovir → converted to acyclovir → higher bioavailability HSV keratitis, HZO, prophylaxis; contraindicated in hypersensitivity to acyclovir/valacyclo vir Convenient dosing; similar efficacy to acyclovir Similar to acyclovir; GI better tolerated Famciclovir – Oral Prodrug of penciclovir → inhibits viral DNA synthesis HZO, suppression of genital HSV; contraindicated in hypersensitivity to famciclovir/penciclo vir Long half-life → less frequent dosing; decreases postherpetic neuralgia Headache, nausea, GI upset, fatigue Ganciclovir – 0.15% Ophthalmic Gel Guanine analogue → inhibits viral DNA polymerase HSV keratitis; contraindicated in hypersensitivity Comparable efficacy to acyclovir ointment; more comfortable Mild irritation, blurred vision
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 49 | P a g e drprabhatdevkota@gmail.com ANTIGLAUCOMA MEDICATIONS INTRODUCTION Intraocular pressure (IOP) depends on: 1. Rate of aqueous humor production 2. Trabecular (conventional) outflow 3. Uveoscleral (unconventional) outflow 4. Episcleral venous pressure Lowering IOP is the only proven method to prevent glaucoma progression. MECHANISM-BASED CLASSIFICATION 1. Drugs Increasing Aqueous Outflow • Uveoscleral: Prostaglandin analogues, EP2 agonists --- 25-35% • Trabecular: Cholinergics, ROCK inhibitors, Nitric oxide donors 2. Drugs Decreasing Aqueous Production • β-blockers --- 20-30% • Carbonic anhydrase inhibitors --- 15-20% • α₂-adrenergic agonists --- 15-20% 3. Drugs Reducing Vitreous Volume • Hyperosmotic agents Q.Disadvantages of Using Two Separate Drugs • Poor compliance • Difficult dosing schedule • Washout effect • Increased preservative toxicity • Higher cost Q.Advantages of Fixed Combinations • Simple dosing • Better compliance • Avoids washout effect • Greater IOP reduction • Less preservative exposure • Reduced systemic toxicity • More economical
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 50 | P a g e drprabhatdevkota@gmail.com I. PROSTAGLANDIN ANALOGUES (PGAs) Class • PGF2α derivatives / Prostamides / Eicosanoids Drugs • Latanoprost 0.005% – once daily (qHS) • Travoprost 0.004% – qHS – good effect over diurnal variation & BAK free formulation • Bimatoprost 0.01% / 0.03% – qHS • Tafluprost 0.0015% – qHS • Unoprostone 0.15% – BID • Latanoprostene bunod 0.024% – qHS Mechanism of Action (PG Depth) • FP receptor agonists in: Ciliary muscle & Sclera • ↑ Matrix metalloproteinases (MMP-1, MMP-9) • ↓ Collagen types I & III • Extracellular matrix remodeling • ↑ Intermuscular spaces → ↑ uveoscleral outflow Latanoprostene bunod 0.024% • Releases nitric oxide (NO) • NO → guanylate cyclase → ↑ cGMP • Relaxes trabecular meshwork + Schlemm canal • Dual outflow enhancement IOP Reduction • 25–35% (maximum among topical drugs) • Bed Time – max efficacy & decreased ADR d/t vasodilation • Flat diurnal curve • Peak: 10–14 hours • Full effect: 4–6 weeks Indications • Primary open-angle glaucoma (POAG) • Ocular hypertension • Normal-tension glaucoma (NTG) • Secondary open-angle glaucoma • Selected chronic angle-closure cases Contraindications (Relative) • Active uveitis (↑ inflammation) • Hypersensitivity • Herpetic keratitis (reactivation) • Aphakia / posterior capsular rent → CME • Recent intraocular surgery
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 51 | P a g e drprabhatdevkota@gmail.com • Pregnancy (relative)—1st T: abortion & 3rd T: Induction of labor • Contact Lens wear Adverse Effects Ocular • Conjunctival hyperemia • Iris pigmentation • Eyelash hypertrichosis • Fornix shortening • Periorbital fat atrophy (PAP) • Rare CME, anterior uveitis (Iritis) • Reactivation of viral keratitis (HSV) Systemic • No systemic ADR • Headache & myalgia (rare) PG Exam Pearls • First-line drug for POAG • Best nocturnal IOP control • Once-daily bedtime dosing • Switch within PG class if non-responder • Remove contact lenses before instillation • DOC in uveitic glaucoma: Timolol, Brimonidine, Dorzolamide • Benefits of PG: Single dosing, 30- 35% IOP reduction, Flat IOP curve, Nil systemic ADR • Ways to decrease systemic absorption: Punctal Occlusion, Closing eyes for 3 minutes • Advantages of Dorzolamide–Timolol (DT) o Greater IOP reduction than either drug alone o Additive/synergistic effect o Better efficacy o No electrolyte imbalance (unlike systemic CAIs) Indications for Surgery in Glaucoma • Failure to achieve target IOP. • Progressive glaucomatous damage despite maximal medical therapy (3 drugs for ≥3 months). • Drug intolerance. • Poor compliance with medical therapy.
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 52 | P a g e drprabhatdevkota@gmail.com II. BETA-ADRENERGIC BLOCKERS Class • Non-selective and β₁-selective blockers Drugs Cardioselective β₁-Blocker • Betaxolol 0.25–0.5% – BD (β₁-selective) Non-Selective β-Blockers • Timolol 0.25–0.5% – BD • Levobunolol 0.25–0.5% – OD/BD • Carteolol 1% – BD Ideal Time: Morning – blunt early morning increased IOP d/t circidian rhythm Mechanism of Action • Block β-receptors in non-pigmented ciliary epithelium • ↓ Adenyl cyclase → ↓ cAMP • ↓ Na⁺/K⁺ ATPase activity • ↓ aqueous humor production IOP Reduction: 20–30%, Reduced nocturnal efficacy Indications • POAG, Secondary glaucomas, Add-on to PGAs Contraindications • Bronchial asthma, COPD • Sinus bradycardia • Heart block • Congestive heart failure • Diabetes mellitus • Peripheral vascular disease • Myasthenia gravis Adverse Effects Ocular • Dry eye, Superficial punctate keratitis, Corneal anesthesia Systemic • Bradycardia • Hypotension • Bronchospasm • Depression, fatigue • Masked hypoglycemia PG Exam Pearls • Avoid bedtime dosing (systemic hypotension) • Betaxolol safer in pulmonary disease (less potent) • Long-term drift & short-term escape phenomenon
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 53 | P a g e drprabhatdevkota@gmail.com III. ALPHA-2 ADRENERGIC AGONISTS Drugs • Brimonidine 0.1–0.2% – TDS— Alphagan-Z (0.1%),Alphagan-P (0.15%),Alphagan (0.2%) • Apraclonidine 0.5–1% – TDS (short-term) – decrease aqueous production Mechanism of Action • Presynaptic α₂ stimulation: o ↓ norepinephrine release o ↓ aqueous production • Postsynaptic α₂: o ↑ uveoscleral outflow • Possible neuroprotective effect IOP Reduction: 20–25% Indications • POAG (adjunct) • Post-laser IOP spike prevention (apraclonidine) Contraindications • Infants & children <2 years--- crosses BBB—Somnolence, Bradycardia, Hypotension, Apnea, CNS depression • MAO inhibitors • Tricyclic antidepressants • Severe cardiovascular disease Adverse Effects • Allergic follicular conjunctivitis • PEEs, decreased Tear production, decreased corneal sensation • Dry mouth • Fatigue • Hypotension • Apnea & CNS depression in infants • Somnolence PG Exam Pearls • Apraclonidine → tachyphylaxis • Brimonidine-Purite better tolerated • Preferred short-term adjunct IV. CARBONIC ANHYDRASE INHIBITORS (CAIs) A. TOPICAL CAIs • Dorzolamide 2% – TDS
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 54 | P a g e drprabhatdevkota@gmail.com • Brinzolamide 1% – TDS Mechanism • Inhibit CA-II in ciliary processes • ↓ bicarbonate → ↓ Na⁺ transport • ↓ aqueous production IOP Reduction • 15–20% B. SYSTEMIC CAIs • Acetazolamide 250 mg QID / 500 mg SR BD --- avoided in Sickle cell—low pH causes more sickling • Methazolamide 50 mg BD–TDS IOP Reduction • 30–40% Indications • Acute angle-closure glaucoma • Pre-operative IOP control • Refractory glaucoma Contraindications • Sulfonamide allergy • Renal failure • Chronic Liver Disease • Renal Transplant • Addison’s disease • Pregnancy Adverse Effects • Ocular: Corneal edema, transient myopia, burning/stinging. • Metabolic: Hyperchloremic metabolic acidosis, hypokalemia, paresthesia. • GU: Renal calculi, nocturia, impotence. • GI: Nausea, vomiting, abdominal pain, GI upset. • Hemato(rare): Aplastic anemia, agranulocytosis, neutropenia, thrombocytopenia. • CNS: Fatigue, Tingling sensation, drowsiness, headache, paresthesia. • Derma (sulfonamide reactions): Rash, pruritus, Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), exfoliative dermatitis. PG Exam Pearls • Most potent aqueous suppressors • Topical CAIs not additive to systemic CAIs • Avoid long-term systemic use
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 55 | P a g e drprabhatdevkota@gmail.com V. CHOLINERGIC AGONISTS (MIOTICS) Drugs • Pilocarpine 0.5–4% – QID (gel qHS) • Carbachol 1.5% – TDS • Echothiophate iodide – BD Mechanism of Action • POAG: M₃ receptor stimulation → Ciliary muscle contraction (longitudinal fibers) → Scleral spur traction → Trabecular meshwork opens (↑ porosity) → ↑ Aqueous outflow via Schlemm's canal → ↓ IOP. • PACG: M₃ receptor stimulation → Miosis → Peripheral iris pulled away from trabecular meshwork → Relieves pupillary block → Opens anterior chamber angle → ↑ Aqueous outflow → ↓ IOP. IOP Reduction: 20–25% Indications • Acute angle-closure glaucoma • Plateau iris syndrome • Post-laser prophylaxis Contraindications • Uveitis • High myopia • Phacolytic glaucoma • Cataract • Neovascular glaucoma • Retinal detachment risk Adverse Effects Ocular • Miosis → poor night vision • Brow ache • Induced myopia – d/t CB contraction • Lacrimation—d/t punctal stenosis • Retinal detachment (rare) Systemic • Bradycardia • Bronchospasm • GI cramps PG Exam Pearls • Oldest antiglaucoma drug • Mainly for acute angle closure • Pilocarpine 0.1% diagnostic for Adie pupil
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 56 | P a g e drprabhatdevkota@gmail.com VI. RHO-KINASE (ROCK) INHIBITORS Drugs – Dose • Netarsudil 0.02% – OD • Ripasudil 0.4% – BD • Netarsudil + Latanoprost – OD Mechanism of Action • Inhibit ROCK-1 & ROCK-2 • ↓ Actin stress fibers • Relax trabecular meshwork • ↑ Schlemm canal permeability • ↓ Episcleral venous pressure IOP Reduction • 20–30% Adverse Effects • Conjunctival hyperemia (most common) • Subconjunctival hemorrhage • Corneal verticillate (Drug causing Verticillate: Amiodarone, HCQ, Chloroquine, Tamoxifen, Indomethacin, RhoKinase Inhibitor) PG Exam Pearls • Only drugs acting directly on trabecular cytoskeleton • Useful in resistant glaucoma Newer Ocular Hypotensive Agents • Natural cannabinoids. • ECM hydrolysis activators (MMPs – Matrix Metalloproteinases) → ↑ Trabecular outflow. • Cytoskeleton modulators → Relax trabecular meshwork. • Ethacrynic acid → Increases trabecular outflow. • Protein kinase inhibitors → Increase aqueous outflow. • cGMP-enhancing compounds → Improve aqueous outflow.
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 57 | P a g e drprabhatdevkota@gmail.com VII. HYPEROSMOTIC AGENTS Drugs – Dose • IV Mannitol 20% IV – 1–2 g/kg over 30–60 min --- less irritating for blood vessel & can be used in DM & CRFpatients. (Instruction: no to get up immediately after injection—causes hypotension) • Oral Isosorbide 45% • Oral Glycerol 50%– 1–1.5 g/kg Mechanism • ↑ Plasma osmolarity • Fluid shift from vitreous → plasma • ↓ Vitreous volume • Rapid IOP reduction ADR • Ocular: Rebound rise in IOP, intraocular hemorrhage. • CNS: Hyperosmolarity causing confusion, disorientation, thirst, chills, and fever. • GI: Nausea, vomiting, diarrhea, and abdominal cramps. • Renal/Fluid & Electrolytes: Diuresis leading to dehydration, hypovolemia, and electrolyte imbalance. • CVS: Angina, pulmonary edema, and congestive heart failure (CHF/CCF). • Others: Hyperglycemia and hypersensitivity reactions. Indications • Acute angle-closure glaucoma • Pre-operative IOP lowering • Malignant Glaucoma Contraindications • Cardiac failure • Renal failure • Anuria • Pulmonary edema • Dehydration • Diabetes (glycerol) PG Exam Pearls • Emergency drugs • Short-acting • Risk of rebound IOP rise
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 58 | P a g e drprabhatdevkota@gmail.com Neuroprotective Drugs in Glaucoma Prevents retinal ganglion cell (RGC) death independent of IOP reduction. ❖ NMDA Receptor Antagonist • Memantine: Blocks glutamate-mediated excitotoxicity → ↓ Ca²⁺ influx → Prevents RGC apoptosis. ❖ Nitric Oxide (NO) Synthase Inhibitor • Aminoguanidine: Inhibits NO-mediated neurotoxicity. ❖ Calcium Channel Blockers • Nimodipine, Verapamil: ↑ Optic nerve blood flow; useful in normal-tension glaucoma (NTG); enhance RGC survival. ❖ Other Neuroprotective Agents • Brimonidine (α₂-agonist): Neuroprotective effect beyond IOP lowering. • Neurotrophic factors: BDNF, CNTF, NGF → Promote RGC survival. • Antioxidants: Resveratrol, α-lipoic acid → Reduce oxidative stress. • Apoptosis inhibitors: Prevent programmed RGC death. • Caspase inhibitors: Block apoptosis pathway. • Coenzyme Q10: Mitochondrial neuroprotection. Newer Drug Delivery Systems in Glaucoma • Durysta® (Bimatoprost intracameral implant): Biodegradable implant; sustained release 3–4 months; FDA-approved (2020) for POAG/OHT. • iDose® Travoprost: Intracameral implant with >6 months sustained release; ~32– 33% IOP reduction. • Bimatoprost ring: Preservative-free forniceal ring containing 13 mg bimatoprost. • Travoprost punctal plug: Inserted into the inferior canaliculus for sustained drug delivery. • Drug-eluting contact lens: Silicone hydrogel lens loaded with nanoparticles for continuous ocular drug release.
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 59 | P a g e drprabhatdevkota@gmail.com Class / Drugs MOA Indication / IOP Reduction Contraindications Key Side Effects / Notes PGAs – Latanoprost, Travoprost, Bimatoprost, Tafluprost, Unoprostone, Latanoprostene bunod ↑ Uveoscleral outflow, ECM remodeling; Latanoprostene bunod: + NO trabecular outflow First-line for POAG, NTG, secondary OAG; IOP↓ 25–35% Relative: recent surgery, uveitis, herpetic keratitis Hyperemia, iris/periocular pigmentation, eyelash growth; bedtime dosing β-Blockers – Timolol, Levobunolol, Carteolol, Metipranolol, Betaxolol ↓ Aqueous production via β1/β2 blockade First- or second-line, additive therapy; IOP↓ 20–30% Asthma, COPD, bradycardia, HF, diabetes, PVD Ocular: burning, hyperemia; systemic: bradycardia, bronchospasm, CNS effects; avoid bedtime dosing α2-Agonists – Brimonidine, Apraclonidine ↓ Aqueous, ↑ uveoscleral outflow; neuroprotective Adjunct therapy, post- laser prophylaxis; IOP↓ 20–25% <2y, MAOIs, tricyclics Allergy, stinging, fatigue, dry mouth; apraclonidine short-term only CAIs – Dorzolamide, Brinzolamide, Acetazolamide, Methazolamide Inhibit carbonic anhydrase → ↓ bicarbonate → ↓ aqueous production Second-line, acute glaucoma, intolerance; Topical ~20%, Oral ~30% Sulfa allergy, renal/hepatic disease, Addison’s Topical: stinging, bitter taste; oral: malaise, acidosis, kidney stones, rare SJS Cholinergics / Miotics – Pilocarpine, Carbachol, Echothiophate Constrict ciliary muscle → ↑ trabecular outflow; pulls iris from TM Acute angle- closure, post- laser prophylaxis; IOP↓ 20–25% Age>40, cataract, uveitis, neovascular glaucoma Miosis, brow ache, headache, myopia; mainly acute use ROCK inhibitors – Netarsudil, Ripasudil Relax TM → ↑ conventional outflow; neuroprotective Adjunct therapy, ocular hypertension, POAG; IOP↓ moderate None absolute Hyperemia, corneal verticillata, mild irritation
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 60 | P a g e drprabhatdevkota@gmail.com Class / Drugs MOA Indication / IOP Reduction Contraindications Key Side Effects / Notes Omidenepag (EP2 agonist) – Omidenepag Isopropyl ↑ Trabecular + uveoscleral outflow via ECM remodeling Alternative / adjunct for latanoprost non- responders, POAG, NTG; IOP↓ 2–5 mmHg None absolute Hyperemia, rare macular edema; no pigmentation changes Hyperosmotics – Mannitol, Glycerol, Isosorbide ↑ Plasma osmolality → water drawn from vitreous Acute IOP reduction, preoperative control, acute angle-closure; rapid IOP↓ Anuria, dehydration, pulmonary edema, cardiac compromise Nausea, headache, electrolyte disturbance; glycerol ↑ glucose
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 61 | P a g e drprabhatdevkota@gmail.com ANTI-VEGF DRUGS Anti-VEGF Intravitreal Injection • Preferred site: Inferotemporal quadrant (Parsplana wide & adv of bells phenomena) • Avoid: 3 & 9 o'clock meridians (long posterior ciliary nerves & arteries) • Pars plana entry: o Phakic: 4 mm o Pseudophakic: 3.5 mm o Aphakic: 3 mm (from limbus) Strategies: 1. Monthly Dosing • Best visual outcomes • High treatment burden 2. Pro Re Nata (PRN) • 3 initial loading doses • Monthly monitoring/ follow-up • Inject when needed (wet) 3. Treat & Extend (TREX) • 3 initial loading doses f/b monthly injection till stability • Gradually extend interval by 1-2 weeks based on CST & BCVA (max: 12 wk, min: 4 wk) • Inject when come 10% Central Subfield Thickness (CST) & 5 letter rule Worsening: • ↑ CST > 10% • ↓ BCVA >5 ETDRS letter (ie. 1 Snellen line) Improving: • ↓ CST > 10% • ↑ BCVA >5 ETDRS letter (ie. 1 Snellen line)
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 62 | P a g e drprabhatdevkota@gmail.com Indications: • Wet AMD/CNV, DME, PDR, RVO with CME, ROP, Myopic CNV • Corneal neovascularization, Pterygium • NVI, NVG Advantages: • Targeted inhibition of pathological angiogenesis • Reduces macular edema, neovascularization, leakage • Prolonged effect with newer agents (Brolucizumab, Faricimab) Complications: • Ocular: Endophthalmitis, ↑IOP, uveitis, retinal detachment, VH, Cataract, SCH (injection related) • Systemic (rare): Stroke, MI, thromboembolic events Contraindications: • Pregnancy, • Active ocular infection/inflammation, • Hypersensitivity, • Recent CVA/MI (relative caution) Mechanism of Action • Pegaptanib: Selectively binds VEGF-165 → blocks VEGFR-1/2 → inhibits angiogenesis and vascular leakage. • Bevacizumab: Binds all VEGF-A isoforms → prevents VEGFR activation → inhibits endothelial proliferation, neovascularization, and leakage. • Ranibizumab: High-affinity VEGF-A binding → blocks VEGFR-mediated angiogenesis and vascular permeability; small Fab fragment → better retinal penetration and low systemic exposure. Newer Anti-VEGF: • Aflibercept: Soluble VEGF trap (VEGFR-1/2 fused to IgG Fc) → binds VEGF-A, VEGF-B, PlGF → inhibits VEGFR signaling and vascular leakage. • Brolucizumab: Small Single Chain Fragent(scFv) binds VEGF-A → high molar dose in small volume → long-lasting intravitreal VEGF inhibition. • Faricimab: Bispecific antibody → 1. VEGF-A inhibition → reduces angiogenesis & leakage, 2. Ang-2 inhibition → stabilizes vessels, reduces vascular inflammation → prolonged durability.
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 63 | P a g e drprabhatdevkota@gmail.com Drug Class / Target MOA MW (kDa) t½ (Vitreous) IVT Dose FDA Pegaptanib (Macugen) Pegylated RNA aptamer / VEGF- 165 Selectively binds VEGF-165 → ↓ angiogenesis & leakage 50 ~10 d 0.3 mg q6 wk 2004 Bevacizumab (Avastin) Full length monoclonal Ab / VEGF-A Binds all VEGF-A → inhibits angiogenesis & leakage 149 ~ 21 d 1.25 mg q4–6 wk Off- label Ranibizumab (Lucentis) Fab fragment / VEGF-A High-affinity VEGF-A inhibition 48 ~ 9 d 0.5 mg q4 wk 2006 Aflibercept (Eylea) Fusion protein / VEGF-A, VEGF- B, PlGF Decoy receptor binds VEGF-A/B & PlGF 115 ~7–9 d 2 mg q8 wk (after loading) 2011 Brolucizumab (Beovu) Single Chain Fragent(scFv) / VEGF-A Small scFv → high molar dose, prolonged VEGF suppression 26 ~3–4 d 6 mg q8– 12 wk 2019 Faricimab (Vabysmo) Bispecific mAb / VEGF-A + Ang- 2 Dual inhibition → anti-VEGF + vessel stabilization 150 ~7.5 d 6 mg q8– 16 wk 2022
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 64 | P a g e drprabhatdevkota@gmail.com PEGAPTANIB (Macugen) Class: Pegylated RNA aptamer (not antibody) MOA Selectively binds VEGF-165 isoform Blocks VEGFR-1 and VEGFR-2 activation ↓ Angiogenesis and vascular leakage Indications Neovascular AMD (historical use) Dose 0.3 mg intravitreal every 6 weeks ADR Injection-related complications Less effective than newer agents BEVACIZUMAB (Avastin) Class: Full-length humanized monoclonal antibody (149 kDa) MOA: Binds all VEGF-A isoforms Prevents VEGFR activation Inhibits endothelial proliferation & leakage Indications • Wet AMD (off-label) • DME • BRVO / CRVO macular edema • ROP • NVG / iris neovascularization • Oncology (systemic)- RCC, Ca Cervix/Ovary, Breast mets, SCC (lungs) Dose 1.25 mg / 0.05 mL intravitreal Monthly or OCT-guided (PRN/T&E) Most cost-effective; off-label use ADR Ocular: Endophthalmitis IOPspike Vitreous hemorrhage Systemic (rare): ↑ BP Thromboembolic events GI bleeding/perforation
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 65 | P a g e drprabhatdevkota@gmail.com RANIBIZUMAB (Lucentis) Class: Monoclonal antibody fragment (Fab) – 48 kDa MOA High-affinity binding to all VEGF-Aisoforms Small size → better retinal penetration Minimal systemic exposure Indications • Wet AMD (FDAapproved 2006) • DME • RVO macular edema • Myopic CNV Dose 0.5 mg / 0.05 mL intravitreal Monthly OR PRN OR Treat-and-Extend ADR Similar to other intravitreal agents Lower systemic risk compared to bevacizumab NEWER ANTI-VEGFs: AFLIBERCEPT (Eylea), BROLUCIZUMAB, FARICIMAB AFLIBERCEPT (Eylea) Class: Receptor-antibody fusion protein (VEGF Trap) – 115 kDa MOA Decoy receptor (VEGFR-1 + VEGFR-2 fused to IgG Fc) Binds: VEGF-A VEGF-B Placental Growth Factor (PlGF) Strong binding affinity Indications • Wet AMD • DME • RVO macular edema • Myopic CNV Dose 2 mg / 0.05 mL 3 monthly loading doses Then every 8 weeks ADR Similar injection risks Rare intraocular inflammation
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 66 | P a g e drprabhatdevkota@gmail.com BROLUCIZUMAB (Beovu) Class: Single-chain antibody fragment (scFv) – 26 kDa MOA Binds VEGF-A Very small size → high molar dose Prolonged VEGF suppression Indications Wet AMD Dose 6 mg intravitreal q8–12 weeks after loading ADR Intraocular inflammation Retinal vasculitis Occlusive retinal vasculitis (rare but serious) FARICIMAB (Vabysmo) Class: Bispecific monoclonal antibody (150 kDa) MOA Dual mechanism: • VEGF-Ainhibition → ↓ angiogenesis & leakage • Angiopoietin-2 inhibition → vessel stabilization, ↓ inflammation Indications Wet AMD DME Dose 6 mg intravitreal Can extend to 12–16 weeks ADR Similar to other anti-VEGF Inflammation possible
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 67 | P a g e drprabhatdevkota@gmail.com IMMUNOSUPPRESSIVE THERAPY (IMT) A. Therapeutic Indications • Failure of high-dose steroids (2–4 weeks) • Inflammation not quiet after 4 weeks • Relapse on tapering • Steroid intolerance / contraindication B. Ocular Severity Indicators Adults: • VA< 20/100 • Severe vitreous haze • Recurrent CME JIA: • Posterior involvement • Glaucoma, cataract • Hypotony, rubeosis C. Diseases Requiring Early IMT (VERY HIGH YIELD) • Behçet disease • VKH • Sympathetic ophthalmia • JIA-associated uveitis • Serpiginous choroiditis • Birdshot chorioretinopathy • Necrotizing scleritis (GPA) • Ocular cicatricial pemphigoid • PUK with systemic vasculitis PRE-TREATMENT EVALUATION (MANDATORY) ✔ CBC ✔ LFT ✔ RFT ✔ Urinalysis ✔ Lipid profile ✔ BP Screen for: • TB (mandatory before TNF inhibitors) • Hepatitis B & C • HIV • Demyelinating disease (avoid TNFi) • Malignancy
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 68 | P a g e drprabhatdevkota@gmail.com • Autoimmune systemic disease Pregnancy counseling: • MTX & MMF contraindicated • Azathioprine relatively safe CLASSIFICATION OFIMMUNOSUPPRESSIVE AGENTS 1. ANTImetabolites (First-Line) Methotrexate (MTX) Mycophenolate mofetil (MMF) Azathioprine (AZA) 2. T-Cell Inhibitors (Calcineurin Inhibitors) Cyclosporine Tacrolimus Sirolimus (mTOR inhibitor) 3. Alkylating Agents (Last Resort) Cyclophosphamide Chlorambucil 4. Biologics TNF-α inhibitors (Adalimumab, Infliximab) IL-6 inhibitor (Tocilizumab) CD20 inhibitor (Rituximab) IL1 Receptor Antagonist: Anakinra, JAK Kinase inhibitors: Tofacitinib
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 69 | P a g e drprabhatdevkota@gmail.com ANTIMETABOLITES (FIRST-LINE AGENTS) 1. METHOTREXATE (MTX) Mechanism ofAction (MOA) Inhibits Dihydrofolate reductase (DHFR) ↓ Tetrahydrofolate → ↓ DNAsynthesis Immunosuppressive effect mainly via: • ↑ Extracellular adenosine • Suppression ofT-cell activation • ↓ Pro-inflammatory cytokines Indications • JIA-associated uveitis ( Pediatric gold standard) • Anterior & intermediate uveitis • VKH • Sympathetic ophthalmia • Serpiginous choroiditis • Ocular cicatricial pemphigoid • Scleritis Contraindications Absolute: • Pregnancy (Teratogenic)
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 70 | P a g e drprabhatdevkota@gmail.com • Chronic liver disease • Active hepatitis • Severe renal failure • Alcohol abuse Relative: • Interstitial lung disease • Cytopenia Prevention of Complication: • Use of Folic Acid • Alcohol abstinence • Contraception for wpmen • Avoid other hepatotoxic drugs Dose Start: 7.5–15 mg/week Increase by 2.5–5 mg every 4 weeks Max: 25 mg/week 15 mg/week → Prefer SC route ✔ Folic acid 1–5 mg/day mandatory Adverse Effects (ADR) Common: • Nausea (most common) • GI upset • Fatigue Serious: • Hepatotoxicity • Bone marrow suppression • Interstitial pneumonitis • Teratogenicity Remarks • Onset: 3–6 months • Monitor CBC, LFT, RFT every 2–3 months • No increased malignancy risk in children (SITE data) • Alcohol abstinence mandatory
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 71 | P a g e drprabhatdevkota@gmail.com 2. MYCOPHENOLATE MOFETIL (MMF) MOA Prodrug → Mycophenolic acid (MPA) Inhibits Inosine Monophosphate Dehydrogenase (IMPDH) Blocks de novo guanosine synthesis Selectively suppresses T & B lymphocytes Indications • Posterior uveitis • Panuveitis • Birdshot chorioretinopathy • Behçet disease • Methotrexate nonresponsive • OCP • Scleritis Contraindications • Pregnancy • Severe active infection • Severe leukopenia
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 72 | P a g e drprabhatdevkota@gmail.com Dose • 500 mg BD (twice daily) initially • Increase to 1 g twice daily • Max: 3 g/day ADR Common: • Diarrhea (most common) • Nausea • GI ulceration Serious: • Leukopenia • Infections • Rare lymphoma Remarks • Onset: 3–4 months • Relatively safer in liver disease • Good option for posterior disease • Monitor CBC & LFT every 4–6 weeks 3. AZATHIOPRINE (AZA) MOA Converted to 6-mercaptopurine Inhibits purine synthesis Affects rapidly dividing lymphocytes Metabolized by TPMT enzyme
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 73 | P a g e drprabhatdevkota@gmail.com Indications Pregnancy (preferred IMT) Sarcoidosis Pars planitis VKH Behçet disease Scleritis JIAiridocyclitis Contraindications • TPMT deficiency • Severe cytopenia • Active malignancy • Relative: • Liver dysfunction Dose 1–2.5 mg/kg/day Start low (25–50 mg/day) → escalate ADR • GI disturbances • Leukopenia • Thrombocytopenia/ Marrow Suppression • Hepatitis/ Hepatotoxicity • Pancreatitis • Secondary Infection • Increased malignancy risk (highest among antimetabolites) Remarks • TPMT (Thiopurine Methyltransferase) testing mandatory before starting (Low/No TPMT: not recommended; Intermediate TPMT: reduced dose, Normal/High TPMT: Higher dose) • Onset: ~4 months • Monitor CBC weekly initially
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 74 | P a g e drprabhatdevkota@gmail.com CALCINEURIN INHIBITORS (T-Cell Inhibitors) 4. CYCLOSPORINE Mechanism ofAction (MOA) • Binds cyclophilin → inhibits calcineurin → ↓ NFAT activation → ↓ IL-2 (± IL-6) transcription → ↓ T-cell activation & cytokine release Ophthalmic Uses Topical (FDAapproved 2002) • Chronic dry eye (KCS) – Sjögren & non-Sjögren (0.05% emulsion) • Corneal Graft Rejection • Meibomian gland dysfunction • Ocular surface inflammation • Severe/refractory VKC (off-label) Systemic • Behçet posterior uveitis • VKH • Birdshot chorioretinopathy • Sympathetic ophthalmia • Sarcoid uveitis • Other autoimmune uveitis Clinical Effects (Topical) • ↓ Ocular surface inflammation • ↑ Goblet cell density • ↑ Baseline tear production (not reflex tearing) • Improves epithelial integrity • ↓ Corneal staining & SPK
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 75 | P a g e drprabhatdevkota@gmail.com • Improves Schirmer test • Steroid-sparing agent Dose Topical • 0.05% emulsion (preservative-free) • BD • Onset: 3–6 months Systemic • 2.5–5 mg/kg/day • Maximum: 10 mg/kg/day Adverse Effects Topical • Burning/stinging (most common) • Minimal systemic absorption Systemic • Nephrotoxicity (dose-limiting) • Neurotoxicity • Hypertension • Gingival hyperplasia • Hypertrichosis • Hirsutism • Hyperlipidemia Contraindications • Uncontrolled hypertension • Renal insufficiency • Malignancy Monitoring • Serum creatinine • Blood pressure High-Yield Pearls • FDA-approved topical immunomodulator for dry eye • Steroid-sparing • Improves baseline tear secretion only • Safe for long-term use • Often combined with other IMTs for uveitis 5.TACROLIMUS Mechanism ofAction (MOA) • Binds FKBP-12 → inhibits calcineurin → ↓ NFAT activation → ↓ IL-2, IL-3, IL-4, TNF-α, IFN-γ → ↓ T-cell activation Exam Pearl: Tacrolimus is ~100× more potent than cyclosporine. Ophthalmic Uses Topical (Off-label)
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 76 | P a g e drprabhatdevkota@gmail.com • Severe VKC • AKC • Steroid-dependent allergic conjunctivitis • Giant papillary conjunctivitis • Ocular GVHD • Ocular cicatricial pemphigoid (adjunct) • Peripheral ulcerative keratitis (adjunct) Systemic • Same indications as cyclosporine • Cyclosporine intolerance Dose Topical • 0.03% ointment • 0.1% ointment (severe disease) • BD; taper after control Systemic • 0.05–0.2 mg/kg/day Advantages • Steroid-sparing • No cataract • No steroid-induced glaucoma (no rise in IOP) • Suitable for long-term therapy • Faster onset than cyclosporine Adverse Effects Topical • Burning/stinging • Transient hyperemia • Herpetic keratitis reactivation • Secondary infection (rare) Systemic • Nephrotoxicity • Neurotoxicity (tremor) • Hyperglycemia/diabetes Contraindications • Active ocular infection • Hypersensitivity • Caution in herpetic keratitis High-Yield Pearls • 100× more potent than cyclosporine • Faster onset • Preferred for severe/refractory VKC &AKC • Fewer cosmetic adverse effects than cyclosporine
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 77 | P a g e drprabhatdevkota@gmail.com ALKYLATING AGENTS (last resort) 6. CYCLOPHOSPHAMIDE MOA Alkylates DNA Cross-linking → cell death Suppresses B & T cells Indications • Necrotizing scleritis • PUK (GPA, PAN, RA) • OCP • Bilateral Mooren ulcer • Severe Behçet Contraindications • Pregnancy • Severe marrow suppression • Active infection Dose 1 mg/kg/day PO OR IV pulse 1 g/m² every 2 weeks ADR • Alopecia • Hemorrhagic cystitis
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 78 | P a g e drprabhatdevkota@gmail.com • Infertility/ Sterility • Reddish urine • Secondary malignancy (bladder CA) • Bone marrow suppression Remarks • Ensure hydration • Monitor urine for hematuria • CBC & Urine Analysis: o WBC: ≥ 3,500–4,000 cells/mm³ o Absolute Neutrophil Count (ANC): > 1,500 cells/mm³ o Platelet Count: > 75,000 cells/mm³
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 79 | P a g e drprabhatdevkota@gmail.com BIOLOGICS Genetically engineered proteins or monoclonal antibodies (mAbs) targeting a specific cytokine, inflammatory cell, or cell-surface receptor. Provide targeted immunomodulation by blocking a key step in the inflammatory cascade. Unlike conventional immunosuppressants, they do not cause global immunosuppression. • Biologics (Biopharmaceuticals): Therapeutic proteins or monoclonal antibodies produced from living organisms using biotechnology. • Biosimilars: Highly similar versions of approved biologics with comparable efficacy, safety, and quality (not identical generics). 7.ADALIMUMAB (only FDAApproved for Uveitis) MOA Fully human monoclonal antibody Binds TNF-α (soluble & membrane-bound) Prevents inflammatory cascade Indications • 1st line: Behçet, JIAuveitis • 2nd line: HLAB27, Posterior uveitis, Intermediate uveitis & Sarcoidosis • Noninfectious intermediate uveitis • Panuveitis Contraindications • Active infection • Latent TB untreated • Multiple sclerosis • Recent malignancy Dose 40 mg SC every 2 weeks Weekly in refractory cases ADR • TB reactivation • Lymphoma risk • Demyelinating disease • Injection site reaction Remarks • Screen TB & Hepatitis B • Onset ~12 weeks • VISUAL & SYCAMORE trials support use
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 80 | P a g e drprabhatdevkota@gmail.com 8. INFLIXIMAB Infliximab is a chimeric anti–TNF-α monoclonal antibody used in refractory non-infectious uveitis. MOA Binds to tumor necrosis factor-alpha (TNF-α) → blocks inflammatory cascade. ↓ Interleukin-6 ↓ Chemokines (e.g., macrophage chemoattractant protein-1) ↓ Adhesion molecules (ICAM-1) Result → potent suppression of ocular inflammation Dose 3–5 mg/kg IV at 0,2,6 weeks Maintenance every 4–8 weeks Primary Indication • Refractory non-infectious uveitis • Behçet’s uveitis • Chronic pediatric uveitis • Severe inflammatory ocular disorders requiring biologics • PUK ADR • Increased susceptibility forTB, Fungal infection • Infusion reaction • Anti-drug antibody formation • TB reactivation • Pulmonary embolism • Congestive heart failure • Lupus-like syndrome • Vitreous hemorrhage Remarks • Rapid onset (6–12 weeks) • Preferred in severe Behçet • Monitor CBC & LFT
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 81 | P a g e drprabhatdevkota@gmail.com 9.TOCILIZUMAB MOA: IL-6 receptor antagonist Indications • Uveitic macular edema • Retinal vasculitis • GCA ADR • Hyperlipidemia • Infection • Elevated LFT Remarks: Best biologic for refractory UME 10. RITUXIMAB MOA Anti-CD20 monoclonal antibody B-cell depletion Indications • ANCAvasculitis • Scleritis • Refractory autoimmune uveitis ADR • Infusion reactions • HBV reactivation • Opportunistic infections
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 82 | P a g e drprabhatdevkota@gmail.com ULTRA-HIGH-YIELD COMPARISON Drug Class + MOA Indications + Contraindications Dose + Onset MajorADR Key Remark s Methotrexat e (MTX) Antimetabolit e (1st line); Inhibits DHFR → ↓ THF → ↓ DNA synthesis; ↑ Adenosine → ↓ T-cell activation Indications: JIAuveitis (gold standard), Anterior/Intermediate uveitis, VKH, SO, Serpiginous, OCP, Scleritis. Contra: Pregnancy, chronic liver disease, severe renal failure, alcohol abuse, ILD 7.5–25 mg/wee k (PO/SC) ; Folic acid mandato ry; Onset: 3–6 mo Hepatotoxicit y, BM suppression, Interstitial pneumonitis, Teratogenicity ; Nausea (MC) Monitor CBC/LF T; No ↑ malignan cy risk in children (SITE); Alcohol abstinenc e Mycopheno late mofetil (MMF) Antimetabolit e; Inhibits IMPDH → ↓ guanosine synthesis → Selective T & B cell suppression Indications: Posterior uveitis, Panuveitis, Birdshot, Behçet, OCP, Scleritis, MTX non- response. Contra: Pregnancy, severe infection, leukopenia 1–3 g/day (BD); Onset: 3–4 mo Diarrhea (MC), Leukopenia, Infection, Rare lymphoma Safer in liver disease; Good for posterior disease Azathioprin e (AZA) Antimetabolit e; Converted to 6-MP → Inhibits purine synthesis; TPMT dependent Indications: Preferred in pregnancy, Sarcoidosis, Pars planitis, VKH, Behçet, JIA. Contra: TPMT deficiency, cytopenia, active malignancy 1–2.5 mg/kg/d ay; Onset: ~4 mo Leukopenia, Hepatitis, Pancreatitis, ↑ Malignancy (highest among antimetabolite s) TPMT testing mandator y; Weekly CBC initially Cyclosporin e Calcineurin inhibitor; Binds cyclophilin → Inhibits calcineurin → ↓ IL-2 → ↓ T-cell activation Indications: Behçet posterior uveitis, VKH, Birdshot, SO, Sarcoid. Contra: Uncontrolled HTN, renal insufficiency, malignancy 2.5–5 mg/kg/d ay; Onset: 4–8 wks Nephrotoxicit y (dose limiting), HTN, Gingival hyperplasia, Hypertrichosis Monitor BP & Creatinin e; Combina tion therapy common Tacrolimus Calcineurin inhibitor; Binds FKBP Indications: CsA intolerance, similar T-cell mediated uveitis. Contra: 0.05–0.2 mg/kg/d ay; Nephrotoxicit y, Neurotoxicity Fewer cosmetic
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 83 | P a g e drprabhatdevkota@gmail.com Drug Class + MOA Indications + Contraindications Dose + Onset MajorADR Key Remark s → Inhibits calcineurin (more potent than CsA) Renal failure, uncontrolled DM Onset: 4–8 wks (tremor), Hyperglycemi a/DM ADR than CsA Cyclophosp hamide Alkylating agent (last resort); DNA alkylation → Cross-linking → B & T cell death Indications: Necrotizing scleritis, PUK (GPA/RA/PAN), OCP, Bilateral Mooren, Severe Behçet. Contra: Pregnancy, marrow suppression, infection 1 mg/kg/d ay PO OR IV1 g/m² q2w; Onset: 4–8 wks Hemorrhagic cystitis, Infertility, Bladder CA, BM suppression Hydratio n mandator y; Monitor urine; Target WBC 3500– 4000 Adalimuma b Biologic (Anti-TNF-α, fully human mAb); Blocks TNF- α inflammatory cascade Indications: Noninfectious intermediate/posterior/pan uveitis, JIA, Behçet. Contra: Active infection, untreated TB, MS, recent malignancy 40 mg SC q2w; Onset: ~12 wks TB reactivation, Demyelinatio n, Lymphoma risk, Injection reaction Screen TB & HBV; VISUAL & SYCAM ORE trials Infliximab Biologic (Anti-TNF-α, chimeric mAb) Indications: Severe Behçet (rapid control), refractory posterior uveitis. Contra: Active infection, TB 3–5 mg/kg IV (0,2,6 wks → q4–8w); Onset: 6–12 wks Infusion reaction, Anti- drug antibodies, TB reactivation Faster than ADA; Preferred in fulminant Behçet Tocilizuma b Biologic (Anti-IL-6 receptor) Indications: Refractory uveitic macular edema (best), Retinal vasculitis, GCA. Contra: Active infection Monthly IV/SC; Onset: 8–12 wks Hyperlipidemi a, ↑ LFT, Infection Best biologic for refractory UME Rituximab Biologic (Anti-CD20); Indications: ANCA vasculitis, refractory IV infusion Infusion reaction, HBV Preferred in
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 84 | P a g e drprabhatdevkota@gmail.com Drug Class + MOA Indications + Contraindications Dose + Onset MajorADR Key Remark s B-cell depletion scleritis, severe autoimmune uveitis. Contra: Active infection, HBV (2 doses 2 wks apart); Onset: 2–3 mo reactivation, Opportunistic infection ANCA- associate d disease FINAL EXAM PEARLS • First-Line & Drug Selection • MTX → Most common first-line IMT • MMF → Strong for posterior/panuveitis • AZA→ Pregnancy-safe IMT • Adalimumab → Only FDA-approved biologic for noninfectious uveitis • JIAchild → MTX →Adalimumab (if refractory) • Pregnancy requiring IMT →Azathioprine • Posterior disease → MMF • Fulminant Behçet → Infliximab • Necrotizing scleritis / PUK → Cyclophosphamide • Life-threatening systemic vasculitis → Cyclophosphamide • Refractory Uveitic Macular Edema (UME) → Tocilizumab • ANCA-associated vasculitis → Rituximab • Always screen TB before TNF inhibitors • Avoid TNF inhibitors in Multiple Sclerosis • Nephrotoxicity → Cyclosporine, Tacrolimus • Hemorrhagic cystitis → Cyclophosphamide • Maintain remission for ≥ 24 months before tapering IMT
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 85 | P a g e drprabhatdevkota@gmail.com SODIUM CHLORIDE (HYPERTONIC SALINE) Mechanism / Pharmacology Sodium chloride is a normal component of tears; 0.9% solution = isotonic with tears. Hypertonic solutions (2%–5%) create an osmotic gradient that draws fluid from the cornea → reduces corneal edema. 5% ointment: maximum effect occurs 3–4 hours after application. Requires an intact epithelium for optimal efficacy; damaged epithelium reduces osmotic effect due to increased penetration of salt. Formulations: 2% solution, 5% solution, 5% ointment. Indications / Clinical Uses Reduction of corneal edema in various conditions: • Bullous keratopathy • Fuchs’ endothelial dystrophy • Post-surgical corneal edema • Acute corneal hydrops in keratoconus (limited efficacy if epithelium is compromised) Dosage / Administration: Drops: 1–2 drops every 3–4 hours; more frequent in early morning for worst vision. Ointment: Nighttime use; less frequent dosing. Special considerations: Hot, dry days may reduce need due to increased tear evaporation. 5% concentration generally more effective than 2%. Side Effects / Adverse Reactions Topical discomfort: stinging, burning, irritation (common, especially 5%) Epistaxis: reported with 2% solution Visual considerations: improves vision, usually outweighs mild discomfort Storage: do not use if solution changes color or becomes cloudy High-Yield Exam Pearls Hypertonic saline works only with intact epithelium; damaged epithelium reduces osmotic effect. 5% ointment → longest-lasting effect; best for nighttime use. For morning corneal edema, several early-morning instillations improve vision. Side effects are generally tolerable and predictable; patient counseling important. Useful in Fuchs’, bullous keratopathy, post-surgical edema.
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 86 | P a g e drprabhatdevkota@gmail.com STAINS IN OPHTHALMOLOGY Feature Fluorescein Sodium Rose Bengal Lissamine Green Indocyanine Green (ICG) Methylen e Blue Light / Excitation Cobalt blue 493 nm → emits 520 nm (green) Visible light → pink/magenta Visible light → green Near-infrared 805 nm → emits 835 nm Absorptio n 660 nm → blue Vital / Non-vital Vital (stains intercellular spaces & damaged epithelium) Non-vital / stains devitalized & unprotected cells Non-vital / stains degenerate & mucus cells Vital for vascular imaging Vital for nerves & devitalized tissue Main Clinical Uses - Corneal/conjuncti val defects- TBUT- Lacrimal drainage test- Goldmann tonometry- Fluorescein angiography- Iris angiography- Aqueous & vitreous fluorophotometry - Dry eye diagnosis- Corneal/conjunctiva l lesions- Edge of herpetic dendritic ulcers - Dry eye evaluation- Conjunctiva l & corneal epithelial cell damage - Retinal & choroidal angiography- Choroidal neovascularizati on detection - Corneal nerve staining- Lacrimal sac visualizati on (DCR)- Lens capsule staining in cataract surgery Advantages / High Yield Bright green fluorescence at physiologic pH, hydrophilic, low toxicity, widely available Highlights devitalized/unprotec ted cells, useful in Sjögren’s Less irritating than rose bengal, longer- lasting staining Near-IR penetrates pigment & hemorrhage, binds plasma proteins → less leakage Stains devitalized cells, mucus, nerves; useful in surgery Disadvantages / Side Effects Topical: mild irritation, stains contact lensesIV: nausea, vomiting, rare allergy, skin/urine discoloration Irritating, phototoxic, may kill cells/virus, stains skin/clothing Minimal irritation, rare allergy Rare allergic reactions, avoid in iodine/shellfish allergy, pregnancy not established Irritating, temporary tissue staining Special Precautions / Allergy, prior severe reaction; Avoid before viral culture of herpetic Avoid contaminati Iodine allergy, shellfish allergy, Allergy to dye; use
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 87 | P a g e drprabhatdevkota@gmail.com Feature Fluorescein Sodium Rose Bengal Lissamine Green Indocyanine Green (ICG) Methylen e Blue Contraindicatio ns careful use in pregnancy lesions; stains skin/clothes on with contact lenses high risk anaphylaxis topical anesthetic to reduce irritation
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 88 | P a g e drprabhatdevkota@gmail.com ANTIALLERGIC DRUGS 1.Topical H1Antihistamines Drugs First-generation: Pheniramine, Antazoline (usually combined with naphazoline) Second-generation: Emedastine, Azelastine, Ketotifen, Olopatadine Pharmacology First-generation: Block H1 receptors → relieve itching, redness, tearing Often combined with decongestants (naphazoline) Second-generation: Selective H1 receptor antagonists Inhibit histamine release from mast cells No effect on α-adrenergic, dopamine, muscarinic, serotonin receptors Onset: 10–20 min Duration: 4–24 h depending on drug Clinical Uses • Seasonal allergic conjunctivitis (SAC) • Perennial allergic conjunctivitis (PAC) • Mild VKC (symptomatic relief) • Relief of ocular itching, redness, chemosis, tearing Side Effects • Burning, stinging, discomfort on instillation • Pheniramine: less stinging than antazoline • Antazoline–naphazoline: mydriasis (light irides), verticillate keratopathy with long-term use • Rare: drug-induced allergy Contraindications • Allergy to components • Narrow-angle glaucoma (risk of mydriasis) • Caution with systemic antihistamines (sedation)
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 89 | P a g e drprabhatdevkota@gmail.com 2. Mast Cell Stabilizers Drugs Cromolyn sodium (2%), Lodoxamide, Nedocromil, Pemirolast, Sodium cromoglycate Pharmacology • Inhibit mast cell degranulation → prevent histamine and mediator release • Additional effects (drug-dependent): • Lodoxamide: inhibits eosinophil migration, leukotriene production; superior to cromolyn in VKC • Nedocromil: inhibits multiple inflammatory cells; faster onset (15–30 min) • Pemirolast: inhibits eosinophil chemotaxis • Azelastine (dual effect): effective in VKC • Mechanism may include inhibition of calcium influx and broader effects on inflammatory cell chemotaxis • Require continuous administration; clinical response may take up to 2 weeks in mild VKC Clinical Uses • SAC, PAC, VKC (especially atopic), GPC • First-line therapy in VKC • Maintenance therapy or adjunct to rapid-acting drugs Dosage 4–6 times/day; maintenance 2 times/day Nedocromil: 2 times/day Side Effects • Burning, stinging, conjunctival injection, itchy/watery eyes • Headache (more with nedocromil, pemirolast) • Minimal systemic absorption Contraindications: Allergy to drug components
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 90 | P a g e drprabhatdevkota@gmail.com 3. Mast Cell–Antihistamine Combinations (Dual-Action Drugs) Drugs Olopatadine, Ketotifen, Azelastine, Epinastine Pharmacology H1 receptor antagonism + mast cell stabilization Inhibit mast cell degranulation, basophil release, eosinophil chemotaxis Drug-specific notes: Olopatadine: high H1 affinity, mild H2/H3; inhibits cytokine production Ketotifen: binds H1/H2/H3; decreases eosinophil activation Azelastine: selective H1; inhibits eosinophil activation Epinastine: weak H2/H3, α1/α2 adrenergic effect; inhibits eosinophil chemotaxis Onset: within minutes Clinical Uses • Ocular itching, allergic conjunctivitis, VKC • Rapid symptomatic relief + long-term prevention • Olopatadine 0.2%: 24-hour duration, once daily • Other dual-action drugs: twice daily dosing Side Effects • Burning, stinging, foreign body sensation, dry eye, pruritus • Systemic: headache, flu-like symptoms, rhinitis • Most common: headache + burning/stinging Contraindications: Allergy to drug components High-Yield Exam Pearls • Mast cell stabilizers = prophylactic, slow onset; prevent degranulation, broader anti- inflammatory effects. • Dual-action drugs (Olopatadine, Ketotifen, Azelastine, Epinastine) = rapid relief + long- term benefit. • First-generation antihistamines = symptomatic relief; may cause mydriasis. • VKC management hierarchy: • Mild → topical antihistamines or mast cell stabilizers • Moderate → dual-action drugs • Severe/resistant → topical cyclosporine ± short-term corticosteroids • Onset: dual-action <10 min; mast cell stabilizers days to 2 weeks. • Dosage frequency: mast cell stabilizers 4–6x/day; dual-action drugs usually 2x/day (Olopatadine 0.2% = once/day).
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 91 | P a g e drprabhatdevkota@gmail.com LOCAL ANESTHETICS I. Ester-linked: (Metabolized by plasma cholinesterase → Higher allergy risk (PABA derivatives) → Shorter acting) • Cocaine • Proparacaine • Procaine • Chloroprocaine • Tetracaine • Benoxinate II.Amide-linked: (Metabolized in liver (hepatic microsomal enzymes)→ Longer acting→ Rare allergy) • Lidocaine • Mepivacaine • Bupivacaine • Etidocaine Lignocaine (Lidocaine) Amide-linked local anesthetic Intermediate potency Intermediate duration of action Mechanism ofAction Blocks voltage-gated sodium channels Prevents Na⁺ influx during depolarization Stabilizes neuronal membrane Reversibly blocks nerve impulse conduction Acts preferentially on: Small Myelinated fibers (pain first) Order of block: Pain → Temperature → Touch → Pressure → Motor Pharmacokinetics • Rapid onset (2–5 min) • Highly lipid soluble • Crosses BBB & placenta • Hepatic metabolism (CYP450) • Metabolites excreted in urine • 60–90 min (without adrenaline) • 90–120 min (with adrenaline) Preparations in Ophthalmology • 2% Lignocaine – most common • 1% (minor procedures)
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 92 | P a g e drprabhatdevkota@gmail.com • With adrenaline (1:100,000 or 1:200,000) • Preservative-free (intraocular use) Dosage Without Adrenaline: Max dose: 3–5 mg/kg With Adrenaline: Max dose: 7 mg/kg Uses in Ophthalmology A. Injectable Anesthesia • Peribulbar block • Retrobulbar block • Sub-Tenon’s anesthesia • Facial nerve block B. Topical Use • 4% solution (less common) • Intracameral use (0.5–1%) C. Intracameral • Used in cataract surgery • Provides analgesia without akinesia Adverse Effects Local Toxicity • Chemosis • Subconjunctival hemorrhage • Myotoxicity (extraocular muscle damage) • Corneal toxicity (with repeated topical use) Systemic Toxicity CNS • Circumoral numbness • Tinnitus • Metallic taste • Dizziness • Seizures • CNS depression • Respiratory arrest Cardiovascular • Hypotension • Arrhythmias • Bradycardia • Cardiac arrest Contraindications
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 93 | P a g e drprabhatdevkota@gmail.com • Severe hepatic disease • Hypersensitivity (rare) • Severe heart block • Caution in elderly & cardiac patients Proparacaine Drug class: Local anesthetic (amide-type) Commercial concentration: 0.5% solution Formulations: With or without 0.25% sodium fluorescein Pharmacology Blocks sodium channels → inhibits nerve impulse conduction → local anesthesia Onset, intensity, and duration similar to tetracaine 0.5% and benoxinate 0.4% Penetration: Less corneal/conjunctival penetration than tetracaine Effect on corneal thickness: Temporary instability (~5 min) after administration → important for pachymetry or refractive surgery measurements Clinical Uses • General-purpose topical anesthesia for: • Slit-lamp procedures • Minor ocular surface surgery • Tonometry, gonioscopy, foreign body removal • Widely accepted by patients due to minimal discomfort on instillation Advantages • Less pain on instillation than tetracaine (~86% of patients preferred) • Minimal irritation • Can be combined with fluorescein for corneal staining Storage Unopened: Room temperature Opened: Keep tightly capped; refrigerate to prevent discoloration Discard if solution is discolored Side Effects Common: Minimal; generally well tolerated Rare: Local allergic hypersensitivity (conjunctival hyperemia, eyelid edema, lacrimation) Allergic contact dermatitis (fingertips in healthcare workers) Cross-sensitivity with tetracaine possible Exacerbation of preexisting Stevens-Johnson syndrome (rare) Transient corneal thickness instability (~5 min)
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 94 | P a g e drprabhatdevkota@gmail.com BOTULINUM TOXIN (BOTOX) FDAapproval: 1978 (for facial dystonias) Most accepted treatment for Benign Essential Blepharospasm (BEB) 90% patients show significant symptomatic improvement Used widely in ophthalmology, oculoplasty, strabismus, cosmetic and therapeutic indications Mechanism ofAction Source Produced by Clostridium botulinum 7 serotypes: A–G Clinical use: Type A(most common) and Type B Action • Blocks acetylcholine (ACh) release at presynaptic neuromuscular junction • Inhibits ACh exocytosis → prevents muscle contraction • Causes temporary chemodenervation • Results in localized muscle paralysis Key Points Effect is reversible Neurotransmission restored in weeks to months Does NOT destroy nerve → causes functional block Potency & Preparation Unit Definition Potency expressed in International Units (IU) 1 IU = LD50 in 50% female Swiss-Webster mice (intraperitoneal injection) Formulation Available as lyophilized freeze-dried powder Vials: 50, 100, 200 units Contains: Human albumin Preservative-free sodium chloride Requires reconstitution with normal saline Final concentration: 2–10 U per 0.1 mL Types of Botulinum Toxin TypeA Most commonly used Brands: Botox® Type B Myobloc® Structurally similar but different molecular constitution Available as liquid (no reconstitution required)
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 95 | P a g e drprabhatdevkota@gmail.com Used in TypeAresistance Dose is 50–100× higher than TypeA Typical dose: 1200–2500 U per eye Indications in Ophthalmology • Benign Essential Blepharospasm (BEB) • Hemifacial spasm • Meige syndrome • Apraxia of eyelid opening • Strabismus (selected cases) • Upper eyelid retraction (thyroid eye disease) • Spastic entropion • Cosmetic indications (crow’s feet) Injection Technique Pre-procedure Antiseptic skin preparation Detailed examination & injection planning Informed consent Pre-injection documentation (photos/video) Optional topical anesthetic (1% lidocaine cream) Post-Procedure Care Avoid strenuous activity for 24 hrs Avoid pressure/massage for 24 hrs Avoid lying face down Avoid alcohol same day No facial massage for 24–48 hrs Cold compress for bruising Resume anticoagulants next day Pharmacodynamics Parameter Value Onset 2–3 days Peak effect 7–10 days Duration 3–4 months Review After 10 days Reinjection required every 3–4 months
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 96 | P a g e drprabhatdevkota@gmail.com Contraindications Absolute • Allergy to Botox/Dysport/Xeomin/Myobloc • Pregnancy • Lactation • Neuromuscular junction disorders: • Myasthenia gravis • ALS • Infection at injection site Relative • Chronic anticoagulant therapy • Drugs decreasing neuromuscular transmission: • Aminoglycosides • Penicillamine • Quinine • Calcium channel blockers Complications • Bruising • Local pain • Ocular • Blepharoptosis (10–15%) → due to levator diffusion • Ectropion • Lagophthalmos • Corneal exposure • Dry eye • Diplopia • Systemic weakness Important Exam Pearls • Gold standard treatment for BEB • Works by blocking ACh release at NMJ • Effect is temporary chemodenervation • Onset: 2–3 days, peak at 7–10 days • Duration: 3–4 months • Ptosis is most common significant complication (10–15%) • Type B used in TypeAresistance • Avoid central pretarsal injection to prevent ptosis • Avoid in myasthenia gravis • 1 IU defined by mouse LD50
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 97 | P a g e drprabhatdevkota@gmail.com MITOMYCIN-C (MMC) Mitomycin-C is an antineoplastic antibiotic isolated from Streptomyces caespitosus. Differentiated from Mitomycin A& B (same organism). First ophthalmic use: 1969 (Japan) – recurrent pterygium. Widely used as an antifibrotic adjunct in ocular surgeries. Chemical & Molecular Profile Chemical formula: C₁₅H₁₈N₄O₅ Alkylating antimetabolite Quinone-containing compound Becomes active after intracellular reduction Preparation: 2 mg MMC vial (powder) & Sterile distilled water for injection required To make 0.02% (0.2 mg/mL) → dissolve 2 mg in 10 mL sterile water. To make 0.04%(0.4 mg/mL) → dissolve 2 mg in 5 mL sterile water. Mitomycin-C (MMC) Preparation for Glaucoma Surgery • MMC vial: 10 mg • Add: 10 mL sterile water • Stock concentration: 1 mg/mL ➢ Phaco + Trabeculectomy: Sponge Application (0.4 mg/mL) • 1 mL of 1 mg/mL MMC o 1.5 mL sterile water • → Final concentration: 0.4 mg/mL ➢ Trabeculectomy Alone: Sponge Application (0.2 mg/mL) • 1 mL of 1 mg/mL MMC o 4 mL sterile water • → Final concentration: 0.2 mg/mL Mechanism ofAction Antimetabolite Alkylating agent Anti-proliferative
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 98 | P a g e drprabhatdevkota@gmail.com Mechanism ofAction Prodrug → activated by intracellular reduction Loss of methoxy group → forms bi-/tri-functional alkylating agent Causes DNAcross-linking N-position of adenine O6 & N-position of guanine Inhibits DNAreplication and transcription Suppresses fibroblast proliferation Produces antifibrotic and antimitotic effect Cell Cycle Effect Maximal effect in: Late G1 phase Early S phase Overall: Cell cycle non-specific alkylating agent Exam Pearl: Acts by DNAcross-linking → inhibition of mitosis → reduced fibrosis & tumor growth. Pharmacokinetics & Bioavailability • Delivered in fully solubilized form • Highly bioavailable when epithelium is denuded • Hydrophobic → penetrates denuded cornea/conjunctiva • Minimal penetration through intact epithelium • No detectable systemic blood levels after topical use Preparation & Storage Reconstituted in sterile water at neutral pH Inactivated in acidic solutions Stored under refrigeration Stable for 2 weeks after reconstitution Clinical Uses in Ophthalmology Major Uses Ocular surface tumors Pterygium surgery Dacryocystorhinostomy (DCR) Strabismus surgery Refractive surgery (PRK) Allergic conjunctivitis MMC in Ocular Surface Tumors Indications Conjunctival SCC OSSN
PG Notes: Drugs in Ophthalmology Dr. Prabhat Devkota, MD 99 | P a g e drprabhatdevkota@gmail.com Recurrent or multifocal lesions Advantages Treats satellite lesions Treats entire ocular surface No need for margin control Dose 0.04% (0.4 mg/ml) QID for 3 weeks Key Point Rapidly cycling tumor cells affected Stem cells relatively spared MMC in Pterygium Surgery Role Prevents recurrence by inhibiting fibroblast proliferation Intraoperative Use 0.02–0.04% (0.2–0.4 mg/ml) Applied over bare sclera Duration: 1–5 minutes Postoperative Use (Older Regimen) 0.04% QID × 2 weeks Evidence-Based Insight Recurrence reduced to ~2% Placebo recurrence ~88% Warning (Exam Favorite) Postoperative prolonged use → severe complications Iritis Secondary glaucoma Corneal edema Cataract Scleral calcification Corneal perforation ⚠ Currently preferred: Short intraoperative application MMC in Dacryocystorhinostomy (DCR) Rationale Failure due to fibrous closure of: Osteotomy site Common canaliculus Use Applied over osteotomy site & flaps 0.02–0.04% Duration: 5–30 minutes