Inflammation and Repair
Introduction:
Inflammation is a fundamental protective response of the body to tissue injury caused by infection, trauma, toxins, or autoimmune reactions. Its primary purpose is to eliminate the cause of injury, remove necrotic cells, and initiate the process of healing. However, if uncontrolled, inflammation itself can lead to tissue damage. Understanding inflammation and repair is essential in pathology and particularly important for optometry students because many ocular diseases—such as conjunctivitis, keratitis, uveitis, and scleritis—are inflammatory in nature.
Definition of Inflammation
Inflammation is the protective vascular and cellular response of living tissue to injury intended to eliminate the initial cause of cell injury, clear out necrotic cells and tissues, and establish repair.
Cardinal Signs of Inflammation (Celsus, Galen):
- Rubor – Redness (due to vascular dilation)
- Calor – Heat (due to increased blood flow)
- Tumor – Swelling (due to exudation of fluid)
- Dolor – Pain (due to chemical mediators & pressure)
- Functio laesa – Loss of function (Virchow’s addition)
Types of Inflammation
1. Acute Inflammation
Acute inflammation is of rapid onset and short duration (minutes to few days). It is characterized by exudation of fluid and plasma proteins (edema) and migration of neutrophils.
Causes:
- Infections (bacterial, viral, fungal)
- Tissue necrosis
- Physical agents (trauma, burns, radiation)
- Chemical agents (toxins, irritants)
Vascular Changes:
- Transient vasoconstriction
- Vasodilation → increased blood flow
- Increased vascular permeability → edema
- Leukocyte emigration (neutrophils first)
Cellular Events:
- Margination and rolling of leukocytes
- Adhesion to endothelium
- Transmigration (diapedesis)
- Chemotaxis (migration towards chemotactic agents)
- Phagocytosis and killing of microbes
Outcomes of Acute Inflammation:
- Resolution (complete healing)
- Suppuration (pus formation)
- Organization & fibrosis (scar formation)
- Progression to chronic inflammation
2. Chronic Inflammation
Chronic inflammation is prolonged, lasting weeks to years, where active inflammation, tissue destruction, and repair occur simultaneously.
Causes:
- Persistent infections (e.g., tuberculosis, leprosy)
- Autoimmune diseases (e.g., rheumatoid arthritis, thyroiditis)
- Prolonged exposure to toxic agents (e.g., silica, asbestos)
Cellular Components:
- Macrophages
- Lymphocytes
- Plasma cells
- Fibroblasts
Special Forms of Chronic Inflammation:
- Granulomatous Inflammation: Characterized by aggregates of activated macrophages (epithelioid cells) surrounded by lymphocytes. Examples: Tuberculosis, Sarcoidosis, Leprosy, Syphilis.
Mediators of Inflammation
Inflammation is regulated by chemical mediators:
- Vasoactive amines: Histamine, serotonin
- Plasma proteases: Complement system, clotting system
- Arachidonic acid metabolites: Prostaglandins, leukotrienes
- Cytokines: TNF-α, IL-1, IL-6
- Reactive oxygen species
Repair and Healing
Repair is the process of restoration of tissue architecture and function after injury. It occurs by two methods:
1. Regeneration
Replacement of injured tissue by proliferation of cells of the same type, restoring normal structure. Example: Liver regeneration after hepatitis.
2. Healing by Fibrosis (Scar Formation)
If regeneration is not possible, tissue is replaced by fibrous scar tissue.
Steps of Healing by Fibrosis:
- Angiogenesis: Formation of new blood vessels from existing ones.
- Fibroblast proliferation: Formation of extracellular matrix and collagen.
- Granulation tissue formation: Highly vascular, pink, soft tissue.
- Scar maturation and remodeling: Collagen becomes dense, vascularity decreases, leading to scar formation.
Types of Wound Healing
- Healing by Primary Intention: Occurs in clean, uninfected surgical wounds with minimal tissue loss. Healing is rapid with little scarring.
- Healing by Secondary Intention: Occurs in large wounds with significant tissue loss, abscess, or ulcers. Healing is slower with more granulation tissue and prominent scar.
Factors Affecting Healing
- Local factors: infection, blood supply, foreign bodies, mobility of wound
- Systemic factors: nutrition (Vitamin C, protein deficiency), diabetes, corticosteroid therapy, age
Ophthalmic Relevance
- Conjunctivitis: Acute inflammation of conjunctiva (bacterial or viral). Clinical signs include redness, swelling, discharge.
- Keratitis: Inflammation of cornea. Healing may result in scarring, impairing vision.
- Uveitis: Chronic inflammation of uveal tract (iris, ciliary body, choroid). May be associated with autoimmune conditions.
- Post-surgical healing: Cataract surgery wounds heal by primary intention; corneal ulcers heal by fibrosis.
- Granulomatous lesions: Tuberculosis and syphilis can cause ocular granulomas.
Infection in General
Introduction:
Infection is defined as the invasion, multiplication, and survival of pathogenic microorganisms within the body of a host. These organisms include bacteria, viruses, fungi, parasites, and chlamydia. Infections are responsible for a wide range of systemic and ocular diseases, and understanding their basic mechanisms is essential for optometry students, as many eye disorders are caused by infectious agents (e.g., conjunctivitis, keratitis, endophthalmitis).
Definition of Infection
Infection refers to the entry and development of pathogenic organisms in the host tissues, leading to disease by causing cell damage, releasing toxins, or triggering immune-mediated injury.
Sources of Infection
- Exogenous: Microorganisms enter from outside the body (air, water, food, contact, fomites, vectors).
- Endogenous: Microorganisms already present in the body (normal flora) become pathogenic under certain conditions (e.g., weakened immunity, trauma, surgery).
Routes of Entry of Infection
- Respiratory tract: Inhalation of droplets (influenza, tuberculosis, COVID-19).
- Gastrointestinal tract: Contaminated food and water (cholera, typhoid, dysentery).
- Skin: Through wounds, burns, insect bites (staphylococcal infections, rabies, malaria).
- Genitourinary tract: Sexual transmission (syphilis, gonorrhea, chlamydia, HIV).
- Transplacental: Mother to fetus (rubella, toxoplasmosis, syphilis).
- Ocular route: Direct contamination of conjunctiva, cornea, or post-surgical wounds (bacterial conjunctivitis, fungal keratitis, post-cataract endophthalmitis).
Types of Infectious Agents
- Bacteria: Single-celled organisms, may produce toxins. Example: Staphylococcus aureus, Mycobacterium tuberculosis.
- Viruses: Obligate intracellular parasites, depend on host machinery for replication. Example: Herpes simplex virus (HSV), adenovirus.
- Fungi: Eukaryotic organisms, produce chronic infections. Example: Aspergillus, Candida.
- Parasites: Protozoa and helminths. Example: Toxoplasma gondii, Plasmodium.
- Chlamydia & Rickettsia: Intracellular organisms causing ocular and systemic diseases.
Host-Microbe Relationship
- Commensalism: Microbe lives in host without causing harm (normal flora of conjunctiva).
- Mutualism: Both benefit (gut bacteria synthesizing vitamins).
- Pathogenicity: Microbe causes disease under normal conditions (e.g., TB bacillus).
- Opportunistic infection: Organisms normally harmless cause disease when immunity is low (fungal infections in HIV/AIDS).
Pathogenesis of Infection
Pathogenesis refers to the mechanism by which an infection produces disease:
- Entry of pathogen: Through respiratory tract, GI tract, skin, or ocular tissues.
- Colonization: Pathogen adheres to host cells (via adhesion molecules).
- Invasion: Spread through tissues and bloodstream.
- Multiplication: Rapid growth inside host.
- Toxin production:
- Exotoxins: Proteins secreted by bacteria (e.g., botulinum toxin, diphtheria toxin).
- Endotoxins: Lipopolysaccharide of Gram-negative bacteria causing septic shock.
- Host immune response: Body reacts with inflammation, antibody production, and cell-mediated immunity.
- Tissue damage: Caused by both microbial toxins and host immune-mediated injury.
Types of Infection
- Localized infection: Restricted to one site (conjunctivitis, corneal ulcer).
- Systemic infection: Spread to multiple organs via blood (septicemia, viral fever).
- Acute infection: Rapid onset, short course (influenza, bacterial conjunctivitis).
- Chronic infection: Long-lasting with relapses (tuberculosis, leprosy).
- Latent infection: Pathogen remains dormant and reactivates later (herpes simplex virus in eye).
- Opportunistic infection: Occurs in immunocompromised patients (fungal keratitis in HIV patients).
- Nosocomial infection: Acquired in hospital settings (post-surgical endophthalmitis).
Defense Mechanisms Against Infection
- Physical barriers: Skin, conjunctiva, corneal epithelium.
- Chemical barriers: Tears containing lysozyme, acidic gastric secretions.
- Phagocytosis: Neutrophils and macrophages engulf pathogens.
- Immune response: Antibody-mediated and cell-mediated immunity.
- Normal flora: Competes with pathogenic bacteria for nutrients and space.
General Manifestations of Infection
- Fever
- Malaise and fatigue
- Increased white blood cell count (leukocytosis)
- Localized pain, swelling, redness
- Ocular involvement: redness, photophobia, blurred vision, purulent discharge
Ophthalmic Relevance
- Bacterial conjunctivitis: Commonly caused by Staphylococcus aureus, Streptococcus pneumoniae.
- Viral conjunctivitis: Adenovirus, highly contagious, presents with watery discharge.
- Fungal keratitis: Occurs after trauma with vegetative matter; caused by Aspergillus, Fusarium.
- Trachoma: Chronic chlamydial infection leading to blindness if untreated.
- Endophthalmitis: Post-surgical or trauma-related severe ocular infection; vision-threatening.
- Ocular TB and syphilis: Systemic infections with ocular manifestations.
Prevention of Infections
- Maintaining hygiene (hand and eye hygiene)
- Safe food and water practices
- Use of sterilized instruments in ophthalmic practice
- Immunization (BCG, MMR, Hepatitis B, COVID-19 vaccines)
- Barrier precautions in clinical practice (gloves, masks, protective eyewear)
- Antimicrobial therapy: antibiotics, antivirals, antifungals, antiparasitics
Specific Infections
Tuberculosis
Introduction:
Tuberculosis (TB) is one of the oldest known infectious diseases caused by Mycobacterium tuberculosis. It remains a major public health problem worldwide, particularly in developing countries like India. While tuberculosis most commonly affects the lungs (pulmonary TB), it can also involve other organs including the eyes (extrapulmonary TB). For optometry and ophthalmology students, understanding ocular manifestations of tuberculosis is very important because undiagnosed ocular TB can lead to chronic inflammation, visual impairment, or even blindness if untreated.
Etiology
- Causative organism: Mycobacterium tuberculosis (acid-fast bacillus, discovered by Robert Koch in 1882).
- Transmission: Primarily airborne spread through inhalation of infected droplets.
- Other sources: Direct inoculation into tissue (rare), hematogenous spread, or lymphatic dissemination from a primary pulmonary focus.
Pathogenesis
The development of tuberculosis involves complex interactions between the bacillus and host immune system:
- Entry: Bacilli enter through respiratory tract and lodge in alveoli.
- Multiplication: They multiply inside alveolar macrophages.
- Immune response: Cell-mediated immunity (T-lymphocytes) attempts to contain infection.
- Granuloma formation: A granulomatous lesion forms consisting of epithelioid cells, Langhans giant cells, lymphocytes, and central caseous necrosis.
- Dissemination: If immunity is weak, bacilli spread through bloodstream to other organs including the eye.
Types of Tuberculosis
- Primary TB: Initial infection in previously unexposed individuals, often in children.
- Secondary TB: Reactivation of latent bacilli, usually in adults, associated with immunosuppression.
- Extrapulmonary TB: Involvement of other organs (lymph nodes, bones, kidneys, meninges, eyes).
Clinical Features (General)
- Persistent cough lasting more than 2 weeks
- Fever, usually low-grade and worse at night
- Weight loss and fatigue
- Night sweats
- Hemoptysis (coughing blood, in pulmonary TB)
Ocular Tuberculosis
Ocular TB can be primary (rare, direct inoculation) or secondary (more common, due to hematogenous spread). Clinical features are often nonspecific, making diagnosis difficult.
Common Ocular Manifestations:
- Eyelids: Lupus vulgaris (chronic skin TB), cold abscess, ulcerative lesions.
- Conjunctiva: Granulomatous conjunctivitis, chronic inflammation, tuberculoma.
- Cornea: Interstitial keratitis, phlyctenular keratoconjunctivitis (seen in children, associated with hypersensitivity reaction).
- Sclera: Nodular or diffuse scleritis, often painful and recurrent.
- Uvea: Granulomatous anterior uveitis, choroidal tubercles, tuberculoma of choroid, choroiditis.
- Retina and optic nerve: Retinitis, neuroretinitis, optic neuritis, papilledema in TB meningitis.
- Lacrimal apparatus: Dacryoadenitis or dacryocystitis due to TB.
Investigations
- Tuberculin Skin Test (Mantoux test): Positive in most cases of latent or active TB, but cannot distinguish between past and current infection.
- Interferon-Gamma Release Assays (IGRAs): Blood test, more specific than Mantoux.
- Chest X-ray: To detect pulmonary TB.
- Sputum examination: Acid-fast bacilli (AFB) by Ziehl-Neelsen staining.
- Polymerase Chain Reaction (PCR): Detects mycobacterial DNA in ocular fluid samples.
- Histopathology: Biopsy of ocular lesions shows granulomas with caseation necrosis.
- Ocular imaging: Fundus fluorescein angiography (FFA) and OCT can detect choroidal involvement.
Complications
- Chronic uveitis leading to synechiae and secondary glaucoma
- Corneal scarring after phlyctenular keratitis
- Choroidal tuberculoma mimicking intraocular tumor
- Vision loss due to optic nerve involvement
- Panophthalmitis in severe cases
Management
The management of tuberculosis requires a combination of systemic anti-tubercular therapy (ATT) along with adjunctive measures for ocular involvement.
1. Systemic Treatment (First-line ATT drugs):
- Isoniazid (H): Bactericidal, inhibits mycolic acid synthesis.
- Rifampicin (R): Inhibits RNA polymerase, potent bactericidal.
- Pyrazinamide (Z): Effective against dormant bacilli.
- Ethambutol (E): Inhibits cell wall synthesis (note: can cause optic neuritis as side effect).
- Streptomycin (S): Second-line drug, aminoglycoside antibiotic.
Standard regimen (DOTS strategy): 2 months of HRZE (intensive phase) followed by 4 months of HR (continuation phase).
2. Ocular Management:
- Topical steroids and cycloplegics: For anterior uveitis.
- NSAIDs: To control inflammation.
- Immunosuppressants: Rarely used if severe inflammation persists despite ATT.
- Surgical management: For complications like cataract, glaucoma, or scleral thinning.
Prevention
- BCG vaccination in children
- Early detection and treatment of pulmonary TB to prevent spread
- Improved nutrition and immunity
- Proper sterilization of ophthalmic instruments
- Use of personal protective equipment (PPE) in clinics
Ocular Importance for Optometrists
- Recognizing ocular signs like phlyctenular keratitis, granulomatous uveitis, or chronic scleritis may be the first clue to systemic TB.
- Optometrists must be aware of ethambutol-induced optic neuritis, a common side effect of TB treatment, which can cause central vision loss and red-green color vision defects.
- Routine visual acuity testing, visual field monitoring, and color vision assessment are important in patients on anti-TB therapy.
Leprosy
Introduction:
Leprosy, also known as Hansen’s disease, is a chronic infectious disease caused by Mycobacterium leprae. It primarily affects the skin, peripheral nerves, mucous membranes, and eyes. Despite significant progress in its control, leprosy continues to be an important public health issue in India and many developing countries. Ocular involvement is common in leprosy, and if not detected early, it can result in blindness. For optometry students, understanding the pathology, clinical presentation, and management of ocular leprosy is essential.
Etiology
- Causative organism: Mycobacterium leprae, discovered by Gerhard Armauer Hansen in 1873.
- Characteristics: Acid-fast bacillus, obligate intracellular parasite, cannot be cultured in artificial media (grows in mouse footpads and armadillos).
- Mode of transmission: Prolonged close contact with untreated patients, mainly via nasal droplets. Rarely through skin contact.
- Incubation period: Long (average 3–5 years, sometimes up to 20 years).
Pathogenesis
Pathogenesis depends on the interaction between M. leprae and host immunity:
- Entry: Bacilli enter through nasal mucosa or skin abrasions.
- Spread: Invade peripheral nerves (especially Schwann cells) and skin.
- Immune response:
- Strong cell-mediated immunity → localized tuberculoid leprosy.
- Weak cell-mediated immunity → widespread lepromatous leprosy.
- Granuloma formation: Epithelioid cells and lymphocytes in tuberculoid type.
- Bacillary proliferation: Extensive multiplication in lepromatous type.
Types of Leprosy
Leprosy presents in a spectrum based on immunity (Ridley-Jopling classification):
- Tuberculoid leprosy (TT): Few skin lesions, asymmetrical nerve involvement, strong immunity, less infectious.
- Lepromatous leprosy (LL): Multiple widespread lesions, symmetric nerve involvement, weak immunity, highly infectious.
- Borderline forms (BT, BB, BL): Intermediate types.
- Indeterminate leprosy: Early, undifferentiated form.
Clinical Features (General)
- Hypopigmented or reddish skin patches with loss of sensation.
- Nodules, plaques, or diffuse infiltration of skin.
- Thickened peripheral nerves (ulnar, posterior tibial, peroneal).
- Muscle weakness and wasting (claw hand, foot drop).
- Loss of eyebrows and eyelashes in lepromatous leprosy (madarosis).
Ocular Leprosy
Ocular involvement occurs in about 20–50% of leprosy patients and is a major cause of blindness. It may result from direct invasion of bacilli, immune-mediated inflammation, or secondary to nerve damage.
1. Eyelid and Adnexa:
- Lagophthalmos (inability to close eyelids due to facial nerve palsy).
- Loss of eyebrows and eyelashes (madarosis).
- Thickened eyelid margins, nodules, or ulcers.
2. Cornea:
- Superficial punctate keratitis.
- Interstitial keratitis (immune reaction).
- Neurotrophic keratitis due to corneal anesthesia.
- Corneal opacities and scarring → visual loss.
3. Uvea:
- Chronic granulomatous iridocyclitis (chronic anterior uveitis).
- Iris pearls (pathognomonic small white nodules on iris surface).
- Seclusio pupillae and secondary glaucoma.
4. Lens:
- Cataract formation (often steroid-induced or due to chronic uveitis).
5. Retina and Optic Nerve:
- Rarely affected, but optic atrophy may occur secondarily.
Investigations
- Slit-skin smear: Demonstration of acid-fast bacilli using Ziehl-Neelsen stain.
- Skin biopsy: Histopathology showing granulomas in tuberculoid type and foamy macrophages with bacilli in lepromatous type.
- Lepromin test: Positive in tuberculoid leprosy, negative in lepromatous type.
- Ocular evaluation: Slit-lamp examination to detect keratitis, uveitis, iris pearls, or corneal anesthesia.
Complications
- Lagophthalmos → exposure keratitis.
- Corneal ulcers and opacities.
- Secondary glaucoma due to chronic uveitis.
- Cataract formation.
- Blindness in advanced untreated cases.
Management
1. Systemic Treatment (WHO Multidrug Therapy – MDT):
- Multibacillary (MB) leprosy: Rifampicin, Clofazimine, and Dapsone for 12 months.
- Paucibacillary (PB) leprosy: Rifampicin and Dapsone for 6 months.
2. Ocular Management:
- Topical corticosteroids: For anterior uveitis.
- Cycloplegics: To prevent synechiae.
- Lubricant eye drops: To prevent exposure keratitis.
- Surgery:
- Tarsorrhaphy for lagophthalmos.
- Cataract extraction if vision significantly impaired.
- Trabeculectomy for glaucoma.
Prevention
- Early detection and complete treatment of patients with MDT.
- Regular ocular screening in all leprosy patients.
- Education regarding eye care and hygiene.
- Protective eyewear for patients with corneal anesthesia.
- Regular follow-up for cataract and glaucoma detection.
Ocular Importance for Optometrists
- Optometrists often encounter patients with lagophthalmos, corneal opacities, or cataracts due to leprosy.
- They play a vital role in early detection of ocular changes during routine eye exams.
- Must monitor visual acuity, intraocular pressure, corneal sensation, and anterior segment changes in leprosy patients.
- Provide low vision aids for patients with irreversible vision loss due to corneal scars or optic atrophy.
Syphilis
Introduction:
Syphilis is a chronic, systemic, sexually transmitted infection caused by the spirochete Treponema pallidum. It is often referred to as the “great imitator” because of its wide range of clinical presentations that resemble many other diseases. The infection progresses through distinct stages—primary, secondary, latent, and tertiary—and can affect multiple organs, including the eye. Ocular syphilis can occur at any stage of the disease and may cause severe visual impairment or blindness if untreated. With the resurgence of syphilis worldwide, particularly in association with HIV infection, optometrists must recognize its ocular signs and understand management principles.
Etiology
- Causative organism: Treponema pallidum, a thin, spiral-shaped, motile spirochete.
- Transmission: Primarily through sexual contact; also transplacental (congenital syphilis), and rarely through blood transfusion.
- Incubation period: About 10–90 days (average ~21 days).
Stages of Syphilis
1. Primary Syphilis
- Painless ulcer (chancre) at site of inoculation (genitalia, rectum, oral cavity).
- Regional lymphadenopathy.
- Heals spontaneously within 3–6 weeks, but spirochetes persist.
2. Secondary Syphilis
- Occurs weeks to months later.
- Generalized maculopapular rash (including palms and soles).
- Mucous patches, condylomata lata.
- Systemic symptoms: fever, malaise, lymphadenopathy.
3. Latent Syphilis
- No clinical symptoms, but serological tests are positive.
- Early latent (<2 and="" late="" latent="" years="">2 years).
4. Tertiary Syphilis
- Occurs years after initial infection.
- Cardiovascular syphilis (aortitis, aneurysm).
- Neurosyphilis (tabes dorsalis, general paresis).
- Gummatous syphilis (granulomatous lesions in skin, bone, and viscera).
Congenital Syphilis
- Transplacental transmission of T. pallidum from infected mother to fetus.
- Early congenital syphilis: Snuffles (nasal discharge), rash, hepatosplenomegaly, bone deformities.
- Late congenital syphilis (after 2 years):
- Hutchinson’s triad: interstitial keratitis, Hutchinson’s teeth (notched incisors), sensorineural deafness.
- Saddle nose deformity, frontal bossing, saber shins.
Ocular Manifestations of Syphilis
Ocular involvement may occur in both acquired and congenital syphilis. It can affect virtually every ocular structure.
1. Eyelids and Conjunctiva
- Primary chancre may rarely occur on eyelids or conjunctiva.
- Chronic conjunctivitis.
2. Cornea
- Interstitial keratitis (especially in congenital syphilis).
- Deep stromal vascularization leading to corneal opacity.
3. Uvea
- Granulomatous anterior uveitis.
- Iris nodules, synechiae, secondary glaucoma.
4. Retina and Choroid
- Syphilitic chorioretinitis (salt-and-pepper fundus).
- Placoid chorioretinitis (common in HIV-associated syphilis).
- Retinal vasculitis, hemorrhages, and exudates.
5. Optic Nerve
- Optic neuritis and optic atrophy in neurosyphilis.
- Papillitis and papilledema.
Investigations
1. Direct Tests
- Dark-field microscopy: Demonstrates motile T. pallidum from chancre.
- PCR (Polymerase Chain Reaction): Detects treponemal DNA.
2. Serological Tests
- Nontreponemal tests: VDRL (Venereal Disease Research Laboratory), RPR (Rapid Plasma Reagin). Useful for screening and monitoring treatment response.
- Treponemal tests: FTA-ABS (Fluorescent Treponemal Antibody Absorption), TPHA (Treponema pallidum Hemagglutination). Highly specific, confirmatory tests.
3. Ocular Evaluation
- Slit-lamp examination for keratitis and uveitis.
- Fundus examination for chorioretinitis, vasculitis, optic neuropathy.
- OCT and fluorescein angiography for retinal and choroidal changes.
Complications
- Corneal opacity and scarring.
- Secondary glaucoma due to synechiae.
- Cataract following chronic uveitis.
- Retinal damage leading to vision loss.
- Optic atrophy causing permanent blindness.
Management
1. Systemic Treatment
- Drug of choice: Benzathine Penicillin G.
- Primary, secondary, and early latent syphilis: Single intramuscular dose of 2.4 million units.
- Late latent and tertiary syphilis: 2.4 million units weekly for 3 weeks.
- Neurosyphilis and ocular syphilis: Intravenous aqueous crystalline penicillin G, 18–24 million units daily for 10–14 days.
- Alternative in penicillin allergy: Doxycycline or Ceftriaxone (though penicillin desensitization is preferred).
2. Ocular Management
- Topical corticosteroids and cycloplegics for uveitis.
- Management of glaucoma with anti-glaucoma drugs or surgery if needed.
- Treatment of complications like cataract or corneal opacity with surgery.
Prevention
- Safe sexual practices and condom use.
- Routine antenatal screening to prevent congenital syphilis.
- Partner notification and treatment to prevent spread.
- Screening for syphilis in HIV patients (and vice versa).
Ocular Importance for Optometrists
- Optometrists may be the first to detect ocular syphilis during eye exams.
- They should be alert to signs such as interstitial keratitis, unexplained uveitis, or chorioretinitis.
- Early referral for systemic evaluation and treatment is crucial to prevent blindness.
- Regular monitoring of visual acuity, intraocular pressure, and fundus changes is essential in treated patients.
Fungal Infections
Introduction:
Fungal infections (mycoses) are caused by a diverse group of eukaryotic organisms ranging from yeasts to filamentous molds. Although less common than bacterial or viral infections, fungal infections of the eye can be sight-threatening and are often more difficult to treat. Ocular mycoses most commonly present as keratitis (corneal infection) or endophthalmitis (intraocular infection) and are frequently associated with specific risk factors such as corneal trauma with vegetative matter, contact lens misuse, ocular surface disease, or systemic immunosuppression. For optometry students and clinicians, early recognition, appropriate sampling for microbiology, and prompt antifungal therapy are essential to preserve vision.
Etiology & Common Causative Organisms
- Filamentous fungi (molds): Fusarium spp., Aspergillus spp., Curvularia, Penicillium. These are common after trauma with plant material and in tropical climates.
- Yeasts: Candida albicans and non-albicans species. Candida causes keratitis and endogenous endophthalmitis, especially in debilitated or fungemic patients.
- Dematiaceous (pigmented) fungi: Alternaria, Cladosporium — often cause corneal or conjunctival infections.
- Cryptococcus neoformans: Can cause meningitis with secondary ocular involvement in immunocompromised hosts.
- Rare pathogens: Pythium insidiosum (not a true fungus but causes aggressive keratitis), Mucorales (mucormycosis — orbital and rhino-orbital disease in diabetic and immunocompromised patients).
Risk Factors & Predisposing Conditions
- Corneal trauma, especially with vegetative matter (thorns, sticks, leaves).
- Poor contact lens hygiene, overnight wear, contaminated solutions.
- Prior topical steroid use or prolonged antibiotic therapy disrupting normal flora.
- Ocular surface disease (dry eye, exposure keratopathy, persistent epithelial defects).
- Systemic immunosuppression (diabetes mellitus, HIV/AIDS, hematologic malignancies, steroid therapy, organ transplantation).
- Recent ocular surgery or penetrating injury (risk of postoperative or post-traumatic fungal endophthalmitis).
Pathogenesis
Fungi typically invade the corneal stroma after an epithelial breach. Filamentous fungi form hyphae that penetrate deep into stroma, producing proteolytic enzymes and provoking a chronic inflammatory response. Yeasts like Candida often cause infection in compromised ocular surfaces or as endogenous seeding from bloodstream. In severe systemic fungemia, organisms can seed the choroid/retina, leading to endogenous fungal endophthalmitis. Mucormycosis (Mucorales) invades blood vessels causing tissue necrosis and rapid orbital spread, representing an ophthalmic emergency.
Clinical Features (Ocular)
Fungal Keratitis
- Onset: Often subacute — slower than bacterial keratitis but may progress rapidly with severe pathogens.
- Symptoms: Pain (variable), redness, photophobia, tearing, reduced vision.
- Signs: Irregular feathery-edged corneal infiltrate, raised dry-appearing surface, satellite lesions, raised sloughing surface, stromal necrosis, hypopyon (sterile or mixed), pigmented lesions with dematiaceous fungi.
- Filamentous organisms (Fusarium, Aspergillus): deep stromal infiltrates with feathery margins and satellite lesions.
- Candida keratitis: often associated with chronic ocular surface disease; may resemble bacterial ulcers and form well-defined dense infiltrates.
Fungal Endophthalmitis
- Exogenous endophthalmitis: after surgery, penetrating trauma, or contaminated injections — presents with severe pain, loss of vision, hypopyon, and vitritis.
- Endogenous endophthalmitis: hematogenous spread (e.g., in candidemia) — often bilateral, with subretinal/retinal lesions, vitritis, and systemic signs.
Rhino-orbital Mucormycosis
- Rapid onset, facial pain, proptosis, ophthalmoplegia, chemosis, black necrotic tissue in nasal/orbital area — common in uncontrolled diabetics or immunocompromised patients.
Investigations
- Corneal scraping: Essential — obtain material from the leading edge and base of the ulcer for direct microscopy and culture.
- Direct microscopy: 10% KOH wet mount with or without calcofluor white (reveals fungal hyphae or yeast). Gram stain, Giemsa may help.
- Culture: Sabouraud dextrose agar, blood agar, and brain–heart infusion media. Culture identifies species and guides therapy though it may be slow.
- Confocal microscopy: In vivo confocal scan can visualize filamentous hyphae in corneal stroma and support rapid diagnosis.
- PCR and molecular tests: Faster identification when available, useful for deep infections or negative cultures.
- Vitreous tap/aspiration and culture: For suspected endophthalmitis.
- Imaging: B-scan ultrasonography (for posterior segment involvement), CT/MRI orbit for suspected mucormycosis or orbital spread.
- Systemic workup: Blood cultures, echocardiography, and searches for systemic foci in endogenous endophthalmitis.
Complications
- Corneal perforation and descemetocele.
- Scarring and irregular astigmatism causing permanent visual loss.
- Endophthalmitis with potential loss of the eye.
- Orbital extension or intracranial spread in mucormycosis — life-threatening.
- Secondary glaucoma from inflammation and steroid response.
Management
Principles
Early diagnosis, appropriate topical/systemic antifungal therapy based on organism and infection severity, surgical intervention when indicated, and management of underlying predisposing factors.
Topical Antifungals
- Natamycin 5% eye drops: First-line for filamentous fungal keratitis (especially Fusarium). Applied hourly initially, then tapered per response.
- Amphotericin B 0.15%–0.5%: Effective for yeast infections like Candida and some molds; used as topical and occasionally intracameral/intravitreous formulations.
- Voriconazole 1%: Broad-spectrum triazole; topical and intrastromal/intravitreal use for recalcitrant cases and Aspergillus infections.
Systemic Antifungals
- Oral voriconazole: Good ocular penetration — used for deep stromal infections and endophthalmitis adjunctively.
- Oral itraconazole/fluconazole: Used selectively (fluconazole for Candida); choice depends on susceptibility.
- Amphotericin B (IV): For systemic or life-threatening fungal infections; has poor ocular penetration unless inflammation is present.
Intracameral / Intravitreal Therapy
- In severe keratitis with impending perforation intrastromal injections of voriconazole or intracameral amphotericin may be used.
- In endophthalmitis, intravitreal amphotericin B and/or voriconazole combined with vitrectomy are mainstays.
Surgical Management
- Therapeutic penetrating keratoplasty (TPK): Indicated for progressive keratitis not responding to medical therapy, impending or frank perforation, or to remove infected tissue.
- Pars plana vitrectomy: For fungal endophthalmitis to remove vitreous load, obtain samples, and allow intravitreal drug delivery.
- Debridement: Repeated superficial debridement may improve topical drug penetration.
- Orbital surgery and debridement: For mucormycosis; may require exenteration in fulminant disease to save life.
Adjunctive Measures
- Stop topical steroids unless specifically indicated under specialist guidance.
- Manage pain, intraocular pressure, and secondary infection.
- Correct underlying systemic immunosuppression when possible (optimize glycemic control in diabetics).
Prevention
- Prompt irrigation and antibiotic prophylaxis after corneal trauma; early ophthalmic review for injuries with vegetative matter.
- Strict contact lens hygiene, avoid overnight wear, use sterile solutions and proper storage.
- Avoid indiscriminate use of topical steroids without microbiological diagnosis.
- In hospitalized or fungemic patients, maintain aseptic intravenous lines and monitor for ocular seeding.
- Early recognition and control of systemic risk factors like diabetes.
Ocular Importance for Optometrists
- Optometrists are often first contact — recognize suspicious corneal ulcers (feathery margins, satellite lesions) and urgently refer for scraping and microbiological workup.
- Understand red flags that warrant immediate referral: rapidly worsening pain, thinning/perforation, hypopyon, or vision deteriorating despite antibiotics.
- Educate contact lens users about hygiene and risks of fungal keratitis.
- Monitor post-operative and immunocompromised patients closely for early signs of fungal infection.
Viral & Chlamydial Infections
Introduction:
Viral and chlamydial infections are major causes of ocular morbidity worldwide. Viruses such as adenovirus, herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV) and others produce a spectrum of disease from self-limiting conjunctivitis to sight-threatening keratitis and retinitis. Chlamydia trachomatis causes both trachoma (a chronic blinding disease) and inclusion conjunctivitis. Early recognition, appropriate laboratory sampling, and timely management (including infection control) are essential for preserving vision and preventing community spread.
Etiology & Important Organisms
- Adenoviruses: Multiple serotypes cause epidemic keratoconjunctivitis (EKC) and pharyngoconjunctival fever.
- Herpes simplex virus (HSV-1, HSV-2): Most ocular HSV is HSV-1 — causes epithelial keratitis (dendritic ulcers), stromal keratitis, blepharoconjunctivitis, and keratouveitis.
- Varicella-zoster virus (VZV): Causes herpes zoster ophthalmicus (HZO) when trigeminal branch is involved — can affect lids, cornea, uvea, retina.
- Cytomegalovirus (CMV): Important in immunocompromised patients — causes CMV retinitis and anterior segment disease (e.g., endothelial disease after transplant).
- Measles and other viral agents: Conjunctivitis and keratitis can occur with systemic viral illnesses.
- Chlamydia trachomatis: Serovars A–C cause trachoma (follicular conjunctivitis → scarring); D–K cause inclusion conjunctivitis and neonatal conjunctivitis (ophthalmia neonatorum).
Pathogenesis — General Principles
Viruses infect ocular surface or intraocular tissues, replicate within host cells, and cause direct cytopathic effects. Some ocular disease results from immune responses to viral antigens (e.g., stromal keratitis is largely immune-mediated). Chlamydia is an obligate intracellular bacterium with an elementary body (infectious) and reticulate body (replicative), producing chronic follicular conjunctivitis and scarring through persistent infection and inflammation.
Clinical Features — Ocular Presentations
Adenoviral Infections
- EKC (epidemic keratoconjunctivitis): Acute onset redness, watery discharge, foreign body sensation, photophobia; often bilateral but not simultaneous. Follicular conjunctivitis, punctate epithelial keratitis, subepithelial infiltrates (seen days–weeks later) which may produce persistent blurred vision.
- Pharyngoconjunctival fever: Conjunctivitis with fever, sore throat, common in children and outbreaks.
Herpes Simplex Virus (HSV)
- Blepharitis/blepharoconjunctivitis: Vesicular eyelid lesions.
- Epithelial keratitis: Dendritic (branching) dendritic ulcer with terminal bulbs — very characteristic. Presents with pain, photophobia, tearing, decreased vision.
- Stromal (interstitial) keratitis: Immune-mediated stromal inflammation causing scarring and vascularisation.
- Disciform keratitis, neurotrophic keratitis, keratouveitis: Possible complications.
Varicella-Zoster Virus (HZO)
- Dermatomal vesicular rash along V1 (ophthalmic) distribution. Ocular signs: conjunctivitis, pseudodendrites, epithelial and stromal keratitis, anterior uveitis, raised intraocular pressure, neurotrophic keratopathy. Risk of severe inflammation and post-herpetic neuralgia.
Cytomegalovirus (CMV)
- CMV retinitis: In immunocompromised patients (e.g., advanced HIV/AIDS) — retinal hemorrhages with “ketchup and cottage-cheese” appearance; rapid, progressive necrosis if untreated.
- Anterior segment CMV: Corneal endotheliitis or hypertensive anterior uveitis in some post-transplant or immunocompetent patients.
Chlamydial Infections
- Trachoma (A–C): Chronic follicular conjunctivitis → repeated episodes → conjunctival scarring, trichiasis, corneal opacity and blindness. Often begins in childhood, with active disease (follicles, intense inflammatory papillae) progressing over years.
- Inclusion conjunctivitis (D–K): Acute/moderate conjunctivitis, mucopurulent discharge, follicles. Neonatal form presents as ophthalmia neonatorum (red, swollen eyes) acquired during birth.
Investigations
- Clinical examination: Slit lamp with fluorescein staining (dendritic ulcers), look for follicles, pseudomembranes, corneal involvement, anterior chamber reaction.
- Laboratory tests:
- PCR/NAAT on conjunctival or corneal swabs — highly sensitive for adenovirus, HSV, VZV, CMV, Chlamydia.
- Direct antigen tests (adenovirus rapid kits) — quick but variable sensitivity.
- Tzanck smear — shows multinucleated giant cells in herpetic lesions (low sensitivity).
- Viral culture — slower, less commonly used clinically.
- Serology — limited role for acute ocular disease but used in systemic/retinal disease workup.
- Ocular fluid PCR (aqueous/vitreous) — used in suspected viral retinitis or atypical uveitis.
Complications
- Corneal scarring, neovascularisation and irregular astigmatism → permanent vision loss (especially after stromal disease or chronic trachoma).
- Recurrent epithelial disease leading to neurotrophic keratitis.
- Secondary bacterial infection of compromised cornea.
- Optic neuritis, retinal necrosis or CMV retinitis causing irreversible visual loss.
- Trichiasis and entropion in trachoma causing corneal damage.
Management — Principles & Specifics
Treatment depends on the agent, site and severity of infection. Avoid indiscriminate steroids without antiviral cover or microbiological confirmation.
Adenoviral Conjunctivitis
- Supportive therapy: cold compresses, lubricants, topical antihistamines/decongestants for comfort.
- Strict infection control (hand hygiene, avoid eye rubbing, disinfection of instruments) to prevent outbreaks.
- Topical steroid: may be used short-term for severe subepithelial infiltrates under ophthalmologist supervision to reduce scarring; monitor for viral persistence.
HSV Ocular Disease
- Epithelial keratitis: Topical antiviral agents (e.g., trifluridine drops or topical acyclovir ointment) are used; topical steroids are contraindicated for active epithelial disease.
- Stromal keratitis/uveitis: Often immune-mediated — treat with systemic antiviral (oral acyclovir) combined with topical corticosteroids and cycloplegics under specialist guidance.
- Consider oral antiviral prophylaxis for recurrent disease.
VZV (HZO)
- Early high-dose oral antiviral therapy (acyclovir/valacyclovir/famciclovir) reduces viral replication and complications — start within 72 hours of rash onset when possible.
- Topical steroids and cycloplegics for uveitis with concurrent antivirals.
- Manage pain and consider referral for neuralgia control.
CMV
- CMV retinitis (immunocompromised): Systemic and/or intravitreal antivirals (ganciclovir, valganciclovir, foscarnet, cidofovir) with close monitoring — usually managed in tertiary care.
- Maintain/improve immune status where possible (e.g., antiretroviral therapy in HIV).
Chlamydial Infections
- Inclusion conjunctivitis: Systemic antibiotics — single dose oral azithromycin 1 g OR doxycycline 100 mg twice daily for 7 days (adult dosing) plus topical tetracycline/erythromycin ointment to reduce local load.
- Trachoma: WHO SAFE strategy:
- S — Surgery for trichiasis
- A — Antibiotics (mass azithromycin distribution where endemic)
- F — Facial cleanliness
- E — Environmental improvement (sanitation, water)
- Neonatal conjunctivitis: Prophylaxis with topical erythromycin ointment at birth and prompt systemic treatment if infected.
Prevention & Public Health
- Hand hygiene, instrument disinfection, and isolation of acute adenoviral cases during outbreaks.
- Safe sexual practices and screening for sexually transmitted infections to reduce ocular chlamydia in adults.
- Neonatal prophylaxis and antenatal screening to prevent congenital infections.
- Mass azithromycin campaigns, improved sanitation, and health education for trachoma control.
- Vaccination where applicable (e.g., measles, varicella) reduces associated ocular complications.
Ophthalmic Importance for Optometrists
- Be alert to characteristic signs (dendritic ulcers for HSV, follicles/pseudomembranes for viral conjunctivitis, chronic follicles/scarring in trachoma) and perform appropriate fluorescein testing and slit-lamp examination.
- Obtain timely conjunctival/corneal swabs for PCR or antigen testing when indicated; do not start steroids empirically on a suspicious ulcer.
- Provide urgent referral for suspected HSV stromal disease, HZO with ocular involvement, CMV retinitis, or trachoma with entropion/trichiasis.
- Educate patients on hygiene and adherence to systemic antiviral/antibiotic therapy and community prevention measures.
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