Comprehensive Notes on Corneal Anatomy, Bacterial Keratitis, and Corneal Disorders

Anatomy and Dimensions of the Cornea

General Characteristics: * The cornea is a transparent, avascular structure forming the anterior $1/6$ of the outer coat of the eyeball. * Refractive Index: $1.37$ . * Refractive Power: $42\,\text{diopters}$ . It provides approximately $2/3$ of the eye's total refractive power and is considered the main refractive medium of the eye.
Dimensions: * Vertical Diameter: $11\,mm$ in adults ( $10\,mm$ in infants). * Horizontal Diameter: $12\,mm$ in adults ( $11\,mm$ in infants). * Thickness: Cornea thickness is measured via pachymetry. It is $0.55\,mm$ to $0.6\,mm$ in the center and increases to $1\,mm$ at the periphery.
Minute Anatomy (5 Layers): 1. Epithelium: * Consists of $5$ to $6$ layers of stratified squamous nonkeratinized cells. * Possesses high regeneration power; complete healing occurs within $24\,\text{hours}$ . * Heals strictly by regeneration (no scarring). 2. Bowman's Membrane: * A superficial condensed layer of the stroma. * Acellular and not capable of regeneration. * Heals by fibrosis, resulting in corneal opacity. 3. Stroma: * Comprises $90\%$ of the total corneal thickness. * Contains $100$ collagen layers that are closely packed, regularly arranged, parallel to the corneal surface, and perpendicular to each other. * Heals by fibrosis. * Cell types at the periphery include fixed keratocytes (fibroblasts) and wandering cells (macrophages). 4. Descemet's Membrane: * A thin, elastic, and highly resistant layer. * Capable of regeneration by the endothelium. * Ends abruptly at the periphery as the Schwalbe line. 5. Endothelium: * A single layer of flat, hexagonal cells. * Cell Density: $4000/mm^2$ at birth, decreasing to $3000/mm^2$ in adults. Numbers decrease with age, and remaining cells increase in size to cover defects. * Clinical Evaluation: Examined by specular microscopy (assessing size, number, and shape). * Functions: * Regeneration of Descemet's membrane. * Serves as a "Pump" for corneal hydration (corneal deturgescence). * Pump Failure: If density falls below $400/mm^2$ , the pump fails, leading to corneal edema.

Physiology and Protective Mechanisms

Nerve Supply: * Exclusively sensory via the Long ciliary nerves (branches from the nasociliary, then ophthalmic/ $V_1$ , then trigeminal nerve). * The epithelium is the most densely innervated surface epithelium in the body. * Sensitivity is $300$ to $600$ times that of the skin; it has the lowest threshold for pain in the body. * The nerves within the cornea are non-myelinated.
Nutrition (Avascularity): * Primary mechanism is diffusion. * Sources: * Limbal capillaries (at the periphery). * Air: Provides $O_2$ . * Aqueous humor: Provides glucose.
Corneal Transparency Factors: * Epithelium is nonkeratinized. * Stroma has a regular collagen arrangement. * Innervation consists of non-myelinated nerves. * Complete absence of blood vessels (avascular). * Few cells (mostly keratocytes). * Active endothelial pump maintains hydration.
Protective Mechanisms: * Eyelid closure (especially during sleep). * Tears: Provide nutrition, contains lysozymes and Epithelium Growth Factor (EGF). * High sensation (triggers blink reflex). * Intact Epithelium: The most important barrier. It cannot be invaded by most pathogens except: * Neisseria gonorrhoeae. * Corynebacterium diphtheriae. * Listeria. * Haemophilus influenzae.

General Clinical Concepts and Bacterial Keratitis

Definitions: * Keratitis: Inflammation of the cornea. * Superficial Keratitis: Involves the epithelium, Bowman's, and superficial stroma. * Interstitial Keratitis: Deep inflammation with an intact epithelium; often due to Ag-Ab reactions. * Corneal Luster: A function of intact epithelium and a healthy tear film.
Predisposing Factors for Ulceration: * General: Decreased immunity, old age, Diabetes Mellitus (DM), malnutrition, and immunosuppressive use. * Local (Loss of defense): Trauma (loss of intact epithelium), exposure (Lagophthalmos).
Causative Organisms: * Common: Pneumococci, Staphylococci, Streptococci. * Contact Lens (CL) users: Pseudomonas.
Pathology Stages: 1. Stage of Infiltration: Localized necrosis caused by organisms/toxins. Includes dilated limbal capillaries and Polymorphonuclear Leukocytes (PMNL) infiltration. Clinically presents as a grey area and ciliary injection. 2. Stage of Ulceration: Necrotic tissue sloughs. * Early: Unclean ulcer (grey, shallow, irregular). * Late: May become a "Clean ulcer" (transparent, deep, smooth) or lead to perforation. 3. Stage of Healing: Epithelium regenerates. Bowman's and stroma heal by vascularization and fibrous tissue. Note: Once vascularized, the cornea is always vascularized.

Clinical Presentation and Complications of Bacterial Ulcers

Symptoms: Severe stitching pain, lacrimation, blepharospasm, photophobia, and dropped vision (due to necrosis, infiltration, or iritis-induced corneal edema).
Signs: * Lid: Edema. * Conjunctiva: Ciliary injection (involvement of anterior ciliary arteries). * Cornea: Loss of luster and positive ( $+Ve$ ) fluorescein test. (Epithelium is hydrophobic; stroma is hydrophilic and absorbs the stain). * Iris/Anterior Chamber (AC): Aqueous flare, muddy iris, and miotic pupil.
Complications of Non-Perforated Ulcer: * Secondary Iritis: Sterile inflammation caused by diffusion of toxins (not the organism itself). * Secondary Glaucoma: Early onset is Open Angle Glaucoma (OAG); late onset may be Closed Angle Glaucoma (CAG) due to Peripheral Anterior Synechia (PAS) formation. * Desmatocele: Herniation of Descemet's membrane due to Intraocular Pressure (IOP). This is rare in children (thin Descemet's) and in hypopyon ulcers (due to posterior abscess formation). * Corneal Opacities: 1. Nebula: Faint opacity. 2. Macula: Medium opacity. 3. Leucoma: Dense white opacity. Peripheral opacities cause vision loss via astigmatism; central ones cause loss via the opacity itself.
Complications of Perforated Ulcer: * Triggered by sudden IOP increase (coughing, straining, crying). * Peripheral Perforation: * Small: Results in PAS and Leucoma adherent (iris prolapse covered by fibrin and scar tissue). * Large: Results in Anterior Staphyloma (weak scar). * Central Perforation: * Small: Leucoma non-adherent (central perforation doesn't trap iris). * Large: May result in a corneal fistula.
Corneal Fistula: * The epithelization of a corneal perforation; a small central hole cannot be closed by the iris. * Diagnosed by hypotony (soft tension), flat AC, and a positive ( $+Ve$ ) Seidel test (River green sign). * Complications include endophthalmitis, macular edema, acquired anterior polar cataract, and secondary glaucoma (PAS or epithelial downgrowth).

Management of Bacterial Corneal Ulcers

Hospitalization Criteria: High-risk ulcers and patients with a single functional eye.
Local Treatment: 1. Antibiotic Eye Drops: Broad-spectrum (e.g., Ciprofloxacine) or fortified drops: Tobramycine ( $-\text{ve}$ ) + Vancomycine ( $+\text{ve}$ ). Adjust after Culture and Sensitivity (C/S). 2. Cycloplegics: Atropine sulphate $1\%$ to reduce pain and PAS formation. 3. Bandage/Patching: Stops lid movement to aid epithelial healing. Contraindicated in purulent conjunctivitis. 4. Bandage Contact Lens: Provides antibiotic delivery and protection.
General Treatment: Bed rest, avoidance of straining, oral NSAIDs for inflammation, and Vitamins A, B, and C.
Treatment of Resistant Cases: * Cauterization: Acute (Hot platinum needle) or Chemical (Carbolic acid, Zinc sulphate for Morax ulcer, Iodine for viral). * Paracentesis: Decreases IOP to reduce perforation risk and washes toxins. * Conjunctival Flap: Promotes healing and reduces perforation risk. * Therapeutic Keratoplasty: High risk of rejection.

Specific Ulcer Types

Hypopyon Ulcer: * Typical: $80\%$ caused by Pneumococci. Associated with chronic dacryocystitis and abrasion. * Atypical: $20\%$ caused by other organisms. * Features: Serpiginous ulcer with two edges: * Healing Edge: Sloping, toward limbus, partially epithelized. * Advancing Edge: Undermined, toward center, no epithelization, dense infiltration. * Note: Descematocele is rare because the posterior abscess causes the membrane to rupture early.
Dendritic (Herpetic) Ulcer (HSV): * HSV Type I: Ocular infection in $75\%$ of cases. The virus is epitheliotropic. * Primary Infection: Usually between $6\,\text{months}$ and $6\,\text{years}$ . Presents with fever and punctate erosions. Virus becomes dormant in the Trigeminal ganglion. * Recurrent Infection: Triggered by stress/fever. Presents with less pain due to hyposthesia. * Morphology: Linear, branching ulcer ending in knobs. Double stain: Rose Bengal (knobs/dead cells) and Fluorescein (ulcer/denuded area). * Atypical Form: Geographical ulcer (often following steroid use). * Disciform Keratitis: Central disc-shaped stromal edema due to an Ag-Ab reaction. * Management: Antivirals like Acyclovir (selectively activated by viral Thymidine Kinase). Debridement is used for dendritic ulcers but contraindicated in geographical ulcers.
Herpes Zoster Ophthalmicus (HZV): * Caused by Varicella-Zoster Virus (Human herpes virus Type 3). It is neurotropic. * Recurrence affects the ophthalmic nerve (unilateral, respects the midline). * Signs include Hutchinson's sign (nasal tip vesicles), interstitial keratitis, and microdendritic ulcers (no knobs). * Treatment: Systemic Acyclovir ( $1 \times 5$ ) and steroids to reduce neuralgia pain.
Fungal/Acanthamoebic Keratitis: * Fungal: History of trauma with vegetable matter. Diagnosed by Giemsa stain. Treated with Natamycin (local) and Itraconazole (systemic). * Acanthamoebic: Associated with CL wear and tap water/saliva. Characterized by severe pain out of proportion to clinical signs. Treated with Brolene and Neomycin.
Non-Infective and Neurologic Ulcers: * Exposure Keratitis (Motor): $7\text{th}$ nerve palsy. Lower $1/3$ of cornea affected due to Bell's phenomenon. Treated with Vitamin A ointment or lateral tarsorrhaphy. * Neurotrophic Keratitis (Sensory): $5\text{th}$ nerve affection. Central cornea affected. Treated with medial tarsorrhaphy or Botox-induced ptosis. * Keratomalacia: Severe Vitamin A deficiency. Results in loss of luster and xerosis. * Interstitial Keratitis: Ag-Ab reaction. Note: Congenital Syphilis triad includes Interstitial Keratitis, Deafness, and Hutchinson's Teeth.

Keratoconus and Keratoplasty

Keratoconus: * Definition: Non-inflammatory conical ectasia of the central cornea due to congenital stromal weakness. * Incidence: Around puberty, progressive, more common in females. Associated with Down, Marfan, and Retinitis Pigmentosa. * Signs: Gradual vision loss (myopia and irregular astigmatism). Munson Sign (angulation of lower lid on downgaze), Vogt striae, Fleischer ring (hemosiderin deposition), and Scissor reflex on retinoscopy. * Management: Hard CL, Intrastromal rings, Cross-linking (Riboflavin + UV), or Keratoplasty. LASIK is contraindicated.
Keratoplasty (Corneal Grafting): * Indications: Visual (opacity), optical (Keratoconus), therapeutic (resistant ulcer), structural. * Contraindications: Uncontrolled glaucoma, dry eye, deep vascularization. * Types: 1. Lamellar: Anterior or Posterior (Endothelial). 2. Penetrating: Full thickness. * Graft Rejection: Early rejection indicates poor donor material; late rejection ( $>6\,\text{months}$ ) is an immune response.