Acute Bronchitis

Acute Bronchitis

Susan Davids, MD, MPH and Ralph M. Schapira, MD in Rakel & Bope: Conn's Current Therapy 2008, 60th ed.

Acute bronchitis is one of the most common diagnoses made by primary care physicians in the United States and accounts for nearly 10 million office visits per year. Acute bronchitis is a transient, self-limited inflammatory process of the upper respiratory tract, specifically the trachea and bronchi. Antibiotics are overprescribed to patients with acute bronchitis; this practice has raised significant concern related to the worldwide rise of antibiotic resistance, which is viewed as one of the world's most pressing public health problems.

Acute bronchitis manifests as an acute respiratory illness of less than 3 weeks' duration, with or without sputum production. Acute bronchitis is a clinical diagnosis and must be distinguished from other respiratory diseases, such as pneumonia, acute exacerbation of chronic bronchitis (episode of worsening of symptoms and expiratory airflow obstruction in patients with chronic obstructive pulmonary disease), and the onset of asthma. Most cases of acute bronchitis occur in the fall and winter. The etiology of acute bronchitis is infectious, and viruses appear to be the cause of most cases. Influenzas A and B are the most common viruses isolated, although a wide variety of infectious agents have been identified, such as adenovirus, coronavirus, parainfluenza virus, respiratory syncytial virus, coxsackievirus, Mycoplasma pneumoniae, Bordetella pertussis, and Chlamydia pneumoniae.

Diagnosis of acute bronchitis is based on findings of a prominent cough that may be accompanied by wheezing and sputum production. Most patients are otherwise healthy and without preexisting respiratory disease. Nonspecific constitutional symptoms may also be part of acute bronchitis. Appropriate management of acute bronchitis is essential because it is one of the most common illnesses that present to physicians in the outpatient setting. Antibiotics are often prescribed unnecessarily for acute bronchitis and other respiratory tract illnesses; these prescriptions may potentially lead to adverse events (i.e., allergic reactions and gastrointestinal side effects) and bacterial resistance. Other medications, such as inhaled bronchodilators and antitussives, are often prescribed for acute bronchitis despite questionable evidence to support their routine use.

Pathophysiology of acute bronchitis involves an acute inflammatory response involving the mucosa of the trachea and bronchi, resulting in injury to the respiratory tract epithelium. Sputum production is increased and bronchoconstriction (potentially resulting in airflow obstruction and wheezing) can occur. Positron emission tomography (PET) of a patient with acute bronchitis confirms that the primary inflammatory changes occur in the trachea and bronchi and not the remainder of the lower respiratory track.

CURRENT DIAGNOSIS

1. Normal healthy adult with cough 2. Predominance of cough 3. Lasts 1 to 3 weeks 4. With or without sputum 5. Can be accompanied by other respiratory and constitutional symptoms 6. Absence of abnormal vital signs and physical exam suggesting pneumonia,particularly Heart rate >100 beats per minute Respiratory rate >24 breaths per minute Temperature >100.4°F (38°C) Lung findings suggest a consolidation process

Diagnosis

Cough, phlegm (which may be purulent as both bacteria and viruses can cause purulent sputum), and wheezing help differentiate acute bronchitis from upper respiratory infections such as pharyngitis and sinusitis. Acute bronchitis must be differentiated from acute bacterial pneumonia. The absence of abnormalities in vital signs (heart rate >100 bpm, respiratory rate >24 breath/min, oral temperature >100.4°F [38°C] and physical examination of the chest) supports the diagnosis of acute bronchitis and makes the need for chest radiography unnecessary in most cases. The treatment and outcome of acute bronchitis and pneumonia are very different; a chest radiograph should always be obtained if there is uncertainty about the diagnosis. Chest radiography will demonstrate no lung infiltrates in a patient with acute bronchitis. In contrast, lung infiltrates are present in pneumonia. Pertussis or whooping cough should be considered in adults with cough in the setting of what appears to be an upper respiratory infection, even in those previously immunized. Typically, the cough of pertussis, unlike acute bronchitis, lasts for longer than 3 weeks. Other respiratory diseases, such as previously undiagnosed asthma, can also mimic acute bronchitis, although several features differentiate asthma from acute bronchitis (see Section 12). Rapid testing to diagnose influenza viruses A and B (the most common causes of acute bronchitis) as a cause of acute bronchitis should be considered given the availability of effective treatment if initiated in the first 48 hours.

Treatment

ANTIBIOTICS, INHALED BRONCHODILATORS, AND ANTITUSSIVES

Existing evidence does not support the routine use of antibiotics for uncomplicated cases of acute bronchitis. Although most cases of acute bronchitis are caused by viral infections, upwards of 60% of patients are prescribed antibiotic therapy, which is contributing to the rise of bacterial resistance to commonly used antibiotics. Meta-analyses examining the effectiveness of antibiotic therapy in patients without underlying lung disease suggest no consistent effect of antibiotics on the severity or duration of acute bronchitis. A recent study evaluated children and patients with colored sputum and found that they also did not benefit from antibiotics. This study also found that compared to other populations, the elderly were less likely to benefit from antibiotics. Smokers with acute bronchitis are even more likely to be prescribed antibiotics.

Their response to antibiotics was either equal to or worse than that of nonsmokers.

CURRENT THERAPY

Antibiotics not routinely recommended If influenza is highly probable and patient is presenting within the first 48 hours, consider treatment with : a. Oseltamivir (Tamiflu) 75 mg PO bid with food for 5 days (influenza A/B) b. Zanamivir (Relenza) 10 mg bid by inhalation for 5 days (influenza A/B) [*] c. Amantadine (Symmetrel) 100 mg bid or 200 mg once daily for 5 days (influenza A) [*] d. Rimantadine (Flumadine) 100 mg bid for 5 days (influenza A) In patients with evidence of bronchial hyperresponsiveness, consider treatment with a. β2-agonists for 1 to 2 weeks b. Antitussives in those with cough for 2 to 3 weeks c. Antipyretics and analgesics as needed d. Smoking cessation Education: cough likely to last 3 weeks or more. ' Due to emergence of antiviral resistance, use of these agents has been discouraged by the CDC.

One possible reason for overuse of antibiotics is the concern by physicians about patient satisfaction. Studies show that patients presenting to the doctor expecting antibiotics were more likely to be prescribed antibiotics; studies also suggest that satisfaction is more related to appropriate patient education than to receiving antibiotics. Patient education should include information regarding the duration of symptoms associated with acute bronchitis. It was found that patients presented on average after 9 days of cough and that the cough persisted for an additional 12 days after the physician visit. This information can impart a realistic expectation of illness duration to the patient.

If influenza is highly suspected and the patient presents within 48 hours of the onset of symptoms, rapid diagnostic testing and treatment should be considered. Both amantadine (Symmetrel) and rimantadine (Flumadine) are effective for influenza A, and neuraminidase inhibitors, inhaled zanamivir (Relenza), and oral oseltamivir (Tamiflu) are effective for influenzas A and B. If these medications are initiated within the first 48 hours of symptoms (and ideally within 30 hours), the duration of illness can be shortened.

The evidence supporting the use of inhaled bronchodilators for the treatment of the symptoms has been variable. Two small trials reported a shorter duration of cough with the use of inhaled ß-agonists; another study reported benefit in those with evidence of bronchial hyperresponsiveness. Current recommendations support the use of ß-agonists only in patients with evidence of bronchial hyperresponsiveness (wheezing or spirometry demonstrating a forced expiration volume in 1 second [FEV₁] <80%>

Antitussive agents have not been shown to improve the acute or early cough but did show some improvements in cough lasting longer than 3 weeks. The current recommendations are to use antitussives, namely dextromethorphan (Benylin) or codeine, in patients with cough of 2 to 3 weeks' duration.

Acute uncomplicated bronchitis is most often a viral illness in which antibiotics are not routinely indicated. Patients presenting with an acute respiratory illness, who are younger than 65 years old without existing pulmonary disease or other significant comorbid illness, should have a thorough physical examination, including vital signs. If the vital signs are normal and physical examination of the chest is clear, pneumonia can most likely be ruled out. In patients who present within 48 hours of onset of symptoms, influenza should be considered as effective therapy is available for acute bronchitis caused by influenzas A or B. Otherwise, the evidence for treatment with antibiotics does not support their routine use. Bronchodilators should be considered in those with evidence of bronchial hyperresponsiveness; cough suppressants should be considered in those with 2 to 3 weeks of cough. Patient education is an integral part of the treatment, and patients should receive information that provides realistic expectations regarding the duration of cough.

Acne Vulgaris

Acne ulgaris

Major points

• Most prevalent skin disorder in pediatrics

1. Affects 40% of children aged 8–10 years
2. Affects 85% of adolescents aged 15–17 years

• Lesion types:

1. Comedones: obstructive lesions
a. Microcomedone: microscopic plugging of the hair follicle that is the precursor lesion to
acne vulgaris
b. Open comedone (blackhead): plugging at the follicular opening; cellular plug of stratum
corneum with oxidized melanin within the follicle (Figure 1)

Figure 1 Comedonal acne - on forehead with open and closed comedones

c. Closed comedone (whitehead): plugging of the pilosebaceous unit just below the
follicular opening with cystic swelling of the duct; filled with cellular debris
2. Inflamatory lesions: papules, pustules, cysts, sinus tracts (Figures 2–4)
3. Scars: depressed, pitted, macular, papular, hypertrophic, keloidal

• Acne is one of the earliest stages of adrenarche
• Lesion type often correlates with pubertal stage
  1. Comedonal acne is predominant type in prepubertal children
  2. Inflammatory acne is more prevalent in adolescents
  

• Develops in areas with high numbers of pilosebaceous units: face, chest, back
• Increased severity often predicted by earlier onset and positive family history of scarring acne
  

Figure 2 Papulopustular acne - numerous erythematous papules and pustules on the face

Figure 3 Cystic acne on the chest with erythematous nodules, crusts and scarring

Figure 4 Inflammatory acne with comedones, erythematous papules and nodules on the back of a teenager

Pathogenesis

• Acne development is a complex process that involves four main contributing factors :
  1. Abnormal keratinization and obstruction of the pilosebaceous unit
  a. Initial lesion is a microcomedone; caused by obstruction of the follicular opening with
  the accumulation of cellular debris
  b. Obstruction is due to abnormal keratinization of the cells lining the follicle with delayed
  shedding and increased cohesiveness
  2. Hormonal stimulation and increased sebum production
  a. Increased secretion and accumulation of sebum within the follicle which is stimulated
  by increased adrenal and gonadal androgens that occur with adrenache
  b. Poly cystic ovary syndrome, a heterogeneous disorder with altered gonadotropin
  secretion, hyperandrogenism (acne, hirsutism and virilization), chronic anovulation,
  obesity and insulin resistance
  3. Bacterial overgrowth
  a. Propionibacterium acnes overgrows within the dilated follicle
  b. Bacterial lipases convert accumulated sebum triglycerides into free fatty acids that
  cause inflammation
  c. P. acnes also releases other proteolytic enzymes and chemotactic factors that further
  stimulate inflammation and recruitment of polymorphonuclear cells (PMNs)
  4. Inflammatory reaction
  a. Inflammatory cells including PMNs are recruited to the area
  b. Ingestion of bacteria by PMNs causes release of hydrolytic enzymes that causes
  rupture of the follicular wall
  c. This leads to intense inflammation and a surrounding foreign body reaction
  

Diagnosis

• Clinical findings

Differential diagnosis

• Drug-induced acne
• Chemical-induced acne
• Rosacea
• Gram-negative folliculitis
• Pityrosporum folliculitis
  

Treatment

• Topical retinoids: important for normalizing keratinization (e.g. tretinoin, adapalene)
• Topical keratolytics: salicylic acid, azelaic acid
• Topical benzoyl peroxide preparations
• Topical antibiotics: clindamycin, erythromycin
• Systemic antibiotics for inflammatory lesions
  1. Doxycycline, tetracycline and minocycline most commonly used in those >9 years of age
• Systemic retinoids for severe cystic acne or early scarring
• Oral contraceptives
  

Prognosis

• Can have significant impact on social interactions and self-esteem and can lead to depression in severe cases
• May produce significant scarring in inflammatory and cystic lesions
• Can rarely be associated with an underlying endocrine disorder
  

References
Cunliffe WJ, Holand DB, Clark SM, Stable GI. Comedogenesis: some new aetiological, clinical and therapeutic strategies. Br J Dermatol 2000; 142: 1084–91
Harper JC, Thiboutot DM. Pathogenesis of acne: recent research advances. Adv Dermatol 2003; 19: 1–10
Lee DJ, VanDyke GS, Kim J. Update on pathogenesis and treatment of acne. Curr Opin Pediatr 2003; 15: 405–10
Leyden JJ. A review of the use of combination therapies for the treatment of acne vulgaris. J Am Acad Dermatol 2003; 49: S200–10
Lucky AW, Biro FM, Simbartl LA, et al. Predictors of severity of acne vulgaris in young adolescent girls: results of a five-year longitudinal study. J Pediatr 1997; 130: 30–9
Weiss JS. Current options for topical treatment of acne vulgaris. Pediatr Dermatol 1997; 14: 480–8

Bullous Pemphigoid

Bullous Pemphigoid

Major points

• Large, tense blisters arising on normal or erythematous skin
• Mucous membrane involvement in 10–35%
• Sites of predilection: lower abdomen, inner thighs, flexor forearms or generalized
• Bullae may have clear or hemorrhagic fluid
  

(Figures 1 and 2)

Figure 1. Bullous pemphigoid - large bullae on erythematous patches

Figure 2. Pemphigoid gestationis - in a young pregnant woman. Her child was unaffected

• Erosions tend to re-epithelialize quickly
• Nikolsky sign is negative
• New vesicles may form at the edge of old blisters
• Blisters do not tend to scar but may be hyperpigmented
• Mild to moderate pruritus
• Early lesions tend to look urticarial
• Rare in childhood
  

Pathogenesis

Bullous pemphigoid (BP) antigens are proteins in the hemidesmosomes (HDs). Autoantibody binds both inside the cell to plaques of HDs and outside cells to the extracellular section of HDs
BP antibodies are directed against both BPAg-1 (230 kDa) component and also BPAg-2 (180kDa) (also called type XVII collagen)

BP IgG can activate complement by the classical pathway causing leukocyte adherence to the basement membrane, degranulation of polymorphonuclear leukocytes and subsequent dermal–epidermal separation

Diagnosis

Histology: Subepidermal blister without necrosis, and superficial dermal infiltrate with lymphocytes, histiocytes and eosinophils
DIF: linear pattern of C3 and IgG at BMZ

Indirect immunoflourescence: 70–80% of patients will have circulating IgG which binds to stratified squamous epithelium; titers do not correlate with disease extent or activity ~50% have elevated IgE, and sometimes eosinophilia, which correlates with pruritus

Differential diagnosis

1. Bullous insect bite reactions
2. Bullous impetigo
3. Bullous erythema multiforme
4. Chronic bullous disease of childhood
   

Treatment

• Prednisone 1–2mg/kg per day until activity is suppressed. Once under control, steroids should be tapered to avoid side-effects
  
• Steroid-sparing agents can be used as an adjunct: cyclophosphamide, azathioprine, cyclosporine, methotrexate, or gold
• Localized BP can be treated with high-potency topical steroids
• Some patients respond to sulfones, tetracycline, or nicotinamide
  

Prognosis
BP may be self-limited and can last several months to many years
Prognosis is good. In adults, half of treated patients go into remission in 2.5–6 years

Venomous Snakebite

Venomous Snakebite

Epidemiology

Venomous snakes (Fig. 1) of the world belong to the families Viperidae (subfamily Viperinae: Old World vipers; subfamily Crotalinae: New World and Asian pit vipers), Elapidae (including cobras, kraits, coral snakes, and all Australian venomous snakes), Hydrophiidae (sea snakes), Atractaspididae (burrowing asps), and Colubridae (a large family, of which most species are nonvenomous and only a few are dangerously toxic to humans). Bite rates are highest in temperate and tropical regions where the population subsists by manual agriculture. Estimates indicate >5 million bites annually by venomous snakes worldwide, with >125,000 deaths.

Figure 1. Types of highly venomous snakes. (A).The Viperidae, (B). The Elapidae, (C). Hydrophiidae (D). Atractaspididae

Snake Anatomy/Identification

The typical snake-venom apparatus consists of bilateral venom glands located below and behind the eye and connected by ducts to hollow, anterior maxillary teeth. In viperids (vipers and pit vipers), these teeth are long mobile fangs that retract against the roof of the mouth when the animal is at rest. In elapids and sea snakes, the fangs are smaller and are relatively fixed in an erect position. In ~20% of pit viper bites and higher percentages of other snakebites (e.g., up to 75% for sea snakes), no venom is released ("dry" bites). Significant envenomation probably occurs in ~50% of all venomous snakebites.

Differentiation of venomous from nonvenomous snake species can be difficult. Viperids are characterized by somewhat triangular heads (a feature shared with many harmless snakes); elliptical pupils (also seen in some nonvenomous snakes, such as boas and pythons); enlarged maxillary fangs; and, in pit vipers, paired heat-sensing pits (foveal organs) on each side of the head. The New World rattlesnakes generally have a series of interlocking keratin plates (the rattle) on the tip of the tail; the rattle is used to warn potentially threatening intruders. Color pattern is notoriously misleading in identifying most venomous snakes. Many harmless snakes have color patterns that closely mimic venomous snakes found in the same region.

Venoms and Clinical Manifestations

Snake venoms are complex mixtures of enzymes, low-molecular-weight polypeptides, glycoproteins, and metal ions. Among the deleterious components are hemorrhagins that promote vascular leakage and cause both local and systemic bleeding. Proteolytic enzymes cause local tissue necrosis, affect the coagulation pathway at various steps, and impair organ function. Myocardial depressant factors reduce cardiac output, and neurotoxins act either pre- or postsynaptically to inhibit peripheral nerve impulses. Most snake venoms have multisystem effects in their victims.

Envenomations by most viperids and some elapids with necrotizing venoms typically cause progressive local swelling, pain, ecchymosis (Fig. 2), and (over a period of hours or days) hemorrhagic bullae and serum-filled vesicles. In serious bites, tissue loss can be significant (Fig. 3). Systemic findings can include changes in taste, mouth numbness, muscle fasciculations, tachycardia or bradycardia, hypotension, pulmonary edema, hemorrhage (from essentially any anatomic site), and renal dysfunction. Envenomations by neurotoxic elapids such as kraits (Bungarus spp.), many Australian elapids [e.g., death adders (Atractaspis spp.) and tiger snakes (Notechis spp.)], some cobras (Naja spp.), and some viperids [e.g., the South American rattlesnake (Crotalus durissus) and some Indian Russell's vipers (Daboia russelii)] cause neurologic dysfunction. Early findings may consist of cranial nerve weakness (e.g., manifested by ptosis) and altered mental status. Severe poisoning may result in paralysis, including the muscles of respiration, and lead to death due to respiratory failure and aspiration. After elapid bites, the time of onset of venom intoxication varies from minutes to hours depending on the species involved, the anatomic location of the bite, and the amount of venom injected. Sea snake envenomation usually causes local pain (variable), myalgias, rhabdomyolysis, and neurotoxicity; these manifestations are occasionally delayed for hours.

Figure 2. Northern Pacific rattlesnake (Crotalus oreganus oreganus) envenomations. Top: Moderately severe envenomation. Note edema and early ecchymosis 2 h after a bite to the finger. Bottom: Severe envenomation. Note extensive ecchymosis 5 days after a bite to the ankle.

Figure3. Early stages of severe, full-thickness necrosis 5 days after a Russell's viper (Daboia russelii) bite in southwestern India

Treatment

Field Management

The most important aspect of prehospital care of a victim bitten by a venomous snake is rapid delivery to a medical facility equipped to provide supportive care (airway, breathing, and circulation) and antivenom administration. Most first aid recommendations made in the past are of little benefit, and some can actually worsen outcome. It is reasonable to apply a splint to the bitten extremity in order to lessen bleeding and discomfort and, if possible, to keep the extremity at approximately heart level. In developing regions, indigenous people should be encouraged to seek care quickly at health care facilities equipped with antivenoms as opposed to consulting traditional healers.

Although mechanical suction has been recommended in the field management of venomous snakebite for many years, there is now evidence that this intervention is of no benefit and can actually be deleterious in terms of local tissue damage.

Techniques or devices used for centuries in an effort to limit venom spread remain controversial. Lympho-occlusive bandages or tourniquets may limit spread only at the cost of greater local tissue damage, particularly with necrotic venoms. Because tourniquets lead to higher rates of amputation and loss of function, they absolutely should not be used. Elapid venoms that are primarily neurotoxic and have no significant local tissue effects may be localized by pressure-immobilization, in which the entire limb is immediately wrapped with a bandage (e.g., crepe or elastic) and then splinted. The wrap pressure must reach ~40–70 mmHg to be effective. Furthermore, if more than a few minutes from medical care, the victim must be carried out from the scene of the bite. Otherwise, muscular pumping will promote venom dispersal, even in bites to the upper extremities. In short, pressure-immobilization should be used only in cases where the offending snake is reliably identified and has a primarily neurotoxic venom, the rescuer is skilled in pressure-wrap application, and the victim can be carried to medical care—an uncommon combination of conditions. Besides tourniquets, other forbidden measures include incising or cooling the bite site, giving the victim alcoholic beverages, and applying electric shocks. The best first aid advice, as coined by Dr. Ian Simpson of the World Health Organization's Snakebite Treatment Group, is to "do it 'RIGHT'": reassure the victim, immobilize the extremity, get to the hospital, and inform the physician of telltale symptoms and signs.

Hospital Management

In the hospital, the victim should be closely monitored (vital signs, cardiac rhythm, oxygen saturation, urine output) while a history is quickly obtained and a rapid, thorough physical examination is performed. Victims of neurotoxic envenomation should be watched carefully for evidence of difficulty swallowing or respiratory insufficiency, which should prompt definitive securing of the airway by endotracheal intubation. To provide objective evidence of the progression of envenomation, the level of swelling in a bitten extremity should be marked and limb circumferences measured in several locations every 15 min until swelling has stabilized. Large-bore IV access in unaffected extremities should be established. Early hypotension is due to pooling of blood in the pulmonary and splanchnic vascular beds. Later, hemolysis and loss of intravascular volume into soft tissues may play important roles. Fluid resuscitation with isotonic saline should be initiated for clinical shock. If the blood pressure response to administration of crystalloid (20–40 mL/kg) is inadequate, a trial of 5% albumin (10–20 mL/kg) is prudent. If tissue perfusion fails to respond to volume resuscitation and antivenom infusion (see below), vasopressors (e.g., dopamine) can be added. Invasive hemodynamic monitoring (central venous and/or pulmonary arterial pressures) can be helpful in such cases, although obtaining access is risky if coagulopathy has developed.

Blood should be drawn for typing and cross-matching and for laboratory evaluation as soon as possible. Important studies include a complete blood count (to evaluate degree of hemorrhage or hemolysis and effects on platelet count), studies of renal and hepatic function, coagulation studies (to identify consumptive coagulopathy), and testing of urine for blood or myoglobin. In developing regions, the 20-min whole-blood clotting test (WBCT) can be used to diagnose coagulopathy reliably. A few milliliters of fresh blood are placed in a new, plain glass receptacle (e.g., test tube) and left undisturbed for 20 min. The tube is then tipped once to 45° to determine whether a clot has formed. If not, coagulopathy is diagnosed. In severe envenomations or with significant comorbidity, arterial blood gas studies, electrocardiography, and chest radiography may be helpful. Any arterial puncture in the setting of coagulopathy, however, requires great caution and must be performed at an anatomic site amenable to direct-pressure tamponade. After antivenom therapy (see below), laboratory values should be rechecked every 6 h until clinical stability is achieved.

The key to management of venomous snakebite is the administration of specific antivenom. Circulating venom components bind quickly with heterologous antibodies produced in animals immunized with the venom in question (or a very closely related venom). Antivenoms may be monospecific (for a particular snake species) or polyspecific (covering several medically important species in the region) but rarely offer cross-protection against snake species other than those used in their production unless the species are known to have homologous venoms. In the United States, assistance in finding antivenom can be obtained 24 h a day from regional poison control centers.

Indications for antivenom administration in victims of viperid bites include any evidence of systemic envenomation (systemic symptoms or signs; laboratory abnormalities) and (possibly) significant, progressive local findings (e.g., soft tissue swelling crossing a joint or involving more than half the bitten limb in the absence of a tourniquet). Care must be used in determining the significance of isolated soft-tissue swelling as, in many countries, the saliva of some relatively harmless snakes causes mild edema at the bite site. In such bites, antivenoms are unhelpful and unnecessary.

In the developing world (e.g., much of Asia and Africa), elapid bites are generally treated similarly to viperid bites. Systemic symptoms such as ptosis, other manifestations of cranial nerve impairment, or respiratory compromise constitute grounds for antivenom administration. Decisions about antivenom administration to victims with isolated local signs or symptoms are based on the criteria listed above for viperid bites.

Production of the only antivenom currently available in the United States for coral snake bites has been discontinued, and remaining stocks will be exhausted or will expire shortly. Until a suitable substitute is produced or imported, physicians caring for victims of Micrurus bites may have to rely on sound supportive care, especially airway management and respiratory support.

The package insert for the selected antivenom can be consulted regarding species covered, method of administration, starting dose, and need (if any) for re-dosing. The information in antivenom package inserts, however, is not always accurate and reliable. Whenever possible, it is advisable for treating physicians to seek advice from experts in snakebite management regarding indications for and dosing of antivenom. For viperid bites, antivenom administration should generally be continued as needed until the victim shows definite improvement (e.g., stabilized vital signs, reduced pain, restored coagulation). Neurotoxicity from elapid bites may be harder to reverse with antivenom. Once neurotoxicity is established and endotracheal intubation is required, further doses of antivenom are unlikely to be beneficial. In such cases, the victim must be maintained on mechanical ventilation until recovery occurs, which may take days to weeks.

The newest available antivenom in the United States (CroFab; Fougera, Melville, NY) is an ovine, Fab fragment antivenom that covers systemic venom effects of all North American pit viper species and carries a low risk of allergic sequelae. Table 1 compares the two antivenoms recently available for the treatment of pit viper bites in the United States. The manufacturer of Antivenin (Crotalidae) Polyvalent has recently discontinued its production, leaving CroFab as the current drug of choice for the management of indigenous pit viper envenomations in the United States. Use of any heterologous serum product carries a risk of anaphylactoid reactions and delayed-hypersensitivity reactions (serum sickness). Skin testing for potential allergy is insensitive and nonspecific and should be omitted. Worldwide, the quality and availability of antivenoms are highly variable. In many developing countries, antivenom resources are scarce, contributing to high morbidity and mortality rates in these regions. The rates of acute anaphylactoid reactions to some of these products exceed 50%. If the risk of allergic reaction is significant, pretreatment with appropriate loading doses of IV antihistamines (e.g., diphenhydramine, 1 mg/kg to a maximum of 100 mg; and cimetidine, 5–10 mg/kg to a maximum of 300 mg) may be considered. In some regions, a prophylactic SC or IM dose of epinephrine is given in an effort to reduce the risk of reaction. Further research is necessary to determine whether any pretreatment measures are truly beneficial. Modest expansion of the patient's intravascular volume with crystalloids could blunt an acute adverse reaction.

Table 1 Comparison of Antivenoms Recently Available for Treatment of Pit Viper Bites in the United States

Antivenin (Crotalidae) Polyvalenta CroFabb Available since 1954 2000 Origin Equine Ovine Snakes used in manufacture Crotalus adamanteus C. adamanteus C. atrox C. atrox C. durissus terrificus C. scutulatus Bothrops atrox Agkistrodon piscivorus Snakes covered All North, Central, and South American and some Asian pit vipers All North American pit vipers (and possibly other Latin American pit vipers) Contains IgG, equine albumin Fab fragments Skin testing recommended by manufacturer Yes No Pretreatment with antihistamines recommended Yes No Dosing (for North American pit viper bites only)c Dry bite None None Mild 0 or 5 vials 4 vials Moderate 10 vials 4–6 vials Severe 15–20 vials 6 vials Repeat dosing As needed Repeat starting dose if patient fails to stabilize. After stabilization, give 2 vials q6h for 3 more doses. (Alternatively, re-dose on an as-needed basis with close observation for recurrence of abnormalities.) Volume of diluent 1000 mLd 250 mL Administer over 2 h 1 h Incidence of anaphylactic/-oid reaction 23–56%e 14%f Incidence of delayed serum sickness 18–86%g 3%

aWyeth-Ayerst Laboratories, Philadelphia, PA. bFougera, Melville, NY. cDegrees of envenomation: mild = progressive local findings (no systemic findings and normal laboratory tests); moderate = local findings plus either mild systemic findings or mild laboratory abnormalities; and severe = local findings plus either severe systemic findings or severe laboratory abnormalities. dReduce for children and for patients with congestive heart failure. eSome reactions have been severe, and some have been fatal. fTo date, all reactions have been relatively mild. gIncidence is higher with larger doses.

Pretreatment is not recommended by the manufacturer of CroFab. Epinephrine should, however, always be immediately available, and the antivenom dose to be administered should be diluted in an appropriate volume of crystalloid according to the package insert. Antivenom should be given only by the IV route, and the infusion should be started slowly, with the physician at the bedside during the initial period to intervene immediately at the first signs of any acute reaction. The rate of infusion can be increased gradually in the absence of a reaction until the full starting dose has been administered (over a total period of ~1 h). Further antivenom may be necessary if the patient's clinical condition fails to stabilize or worsens. After stabilization, additional doses of CroFab are often recommended as the small-molecular-weight Fab fragments are rapidly cleared from the circulation. Larger, whole IgG or F(ab)2 antivenoms have longer half-lives that eliminate the need for re-dosing after initial stabilization unless definitive symptoms of envenomation reappear.

If the patient develops an acute reaction to antivenom, the infusion should be temporarily stopped and the reaction immediately treated with IM epinephrine and IV antihistamine and steroids (Chap. 311). If the severity of envenomation warrants additional antivenom, the dose should be further diluted in isotonic saline and restarted as soon as possible. Rarely, in recalcitrant cases, a concomitant IV infusion of epinephrine may be required to hold allergic sequelae at bay while further antivenom is administered. The patient must be very closely monitored, preferably in an intensive care setting, during such therapy.

Blood products are rarely necessary in the management of the envenomated patient. The venoms of many snake species can cause a drop in platelet count or hematocrit and depletion of coagulation factors. Nevertheless, these components usually rebound within hours after administration of adequate antivenom. If the need for blood products is thought to be great (e.g., for a dangerously low platelet count in a hemorrhaging patient), these products still should be given only after adequate antivenom administration to avoid adding fuel to ongoing consumptive coagulopathy.

Rhabdomyolysis and hemolysis should be managed in standard fashion. Victims who develop acute renal failure should be evaluated by a nephrologist and referred for dialysis (peritoneal or hemodialysis) as needed. Such renal failure, usually due to acute tubular necrosis, is frequently reversible. If bilateral cortical necrosis occurs, however, the prognosis for renal recovery is more grim, and long-term dialysis with possible renal transplantation may be necessary.

Acetylcholinesterase inhibitors (e.g., edrophonium and neostigmine) may promote neurologic improvement in patients bitten by snakes with postsynaptic neurotoxins. Victims with objective evidence of neurologic dysfunction after snakebite should receive a trial of acetylcholinesterase inhibitors as outlined in Table 2. If they respond, additional doses of long-acting neostigmine can be continued as needed. Special vigilance is required to prevent aspiration if repetitive dosing of neostigmine is used in an attempt to obviate endotracheal intubation.

Table 2 Use of Acetylcholinesterase Inhibitors in Neurotoxic Snake Envenomation

1. Patients with clear, objective evidence of neurotoxicity after snakebite (e.g., ptosis or inability to maintain upward gaze) should receive a trial of edrophonium (if available) or neostigmine. a. Pretreat with atropine: 0.6 mg IV (children, 0.02 mg/kg; minimum of 0.1 mg) b. Follow with: Edrophonium: 10 mg IV (children, 0.25 mg/kg) or Neostigmine: 1.5–2.0 mg IM (children, 0.025–0.08 mg/kg) 2. If objective improvement is evident at 5 min, continue neostigmine at a dose of 0.5 mg (children, 0.01 mg/kg) every 30 min as needed, with continued administration of atropine by continuous infusion of 0.6 mg over 8 h (children, 0.02 mg/kg over 8 h). 3. Maintain vigilance regarding aspiration risk, and secure the airway with endotracheal intubation as needed.

Care of the bite wound includes application of a dry sterile dressing and splinting of the extremity with padding between the digits. Once the administration of an indicated antivenom has been initiated, the extremity should be elevated above heart level to relieve edema. Tetanus immunization should be updated as appropriate. Prophylactic antibiotics are generally unnecessary after bites by North American snakes, as the incidence of secondary infection is low. Antibiotics can be considered, however, if misguided first-aid efforts have included incisions or mouth suction. In some regions of the world, secondary bacterial infection is more common and the consequences are dire. In these regions, prophylactic antibiotics (e.g., cephalosporins) are commonly used.

Most snake envenomations involve subcutaneous deposition of venom. On occasion, however, venom can be injected more deeply into muscle compartments. If swelling in the bitten extremity raises concern that subfascial muscle edema may be impeding tissue perfusion (muscle-compartment syndrome), intracompartmental pressures (ICPs) should be checked by any minimally invasive technique—e.g., wick catheter or ICP monitor (Stryker Instruments, Kalamazoo, MI). If any ICP is high (>30–40 mmHg), the extremity should be kept elevated while further antivenom is given. A dose of IV mannitol (1 g/kg) can be given in an effort to reduce muscle edema if the patient's hemodynamic status is stable. If, after 1 h of such therapy, the ICP remains elevated, a surgical consultation for possible fasciotomy should be obtained. While evidence from studies of animals suggests that fasciotomy may actually worsen myonecrosis, compartmental decompression is still required to preserve nerve function. Fortunately, the incidence of muscle-compartment syndrome is very low following snakebite.

Wound care in the days after the bite may require careful aseptic debridement of clearly necrotic tissue once coagulation has been restored. Intact serum-filled vesicles or hemorrhagic blebs should be left undisturbed. If ruptured, they should be debrided with sterile technique.

Physical therapy should be started when pain allows in order to return the victim to a functional state. The incidence of long-term loss of function (e.g., reduced range of motion, impaired sensory function) is unclear but is probably quite high (>30%), particularly after viperid bites.

Any patient with signs of venom poisoning should be observed in the hospital for at least 24 h. In North America, a patient with an apparently "dry" viperid bite should be watched for at least 8 h before discharge, as significant toxicity occasionally develops after a delay of several hours. The onset of systemic symptoms is commonly delayed for a number of hours after bites by several of the elapids (including coral snakes), some non–North American viperids [e.g., the hump-nosed pit viper (Hypnale hypnale)], and sea snakes. Patients bitten by these reptiles should be observed in the hospital for at least 24 h. Unstable patients should be admitted to a monitored setting.

At discharge, victims of venomous snakebite should be warned about signs and symptoms of wound infection and serum sickness as well as other potential long-term sequelae, such as pituitary insufficiency in Russell's viper (D. russelii) bites. If the victim had evidence of coagulopathy early on, this abnormality can recur during the first 2–3 weeks after the bite. Such victims should be warned to avoid elective surgery or activities posing a high risk of trauma during this period. Outpatient analgesic treatment and physical therapy should be continued.

In the event of serum sickness (fever, chills, urticaria, myalgias, arthralgias, and possibly renal or neurologic dysfunction developing 1–2 weeks after antivenom administration), the victim should be treated with systemic glucocorticoids (e.g., oral prednisone, 1–2 mg/kg daily) until all findings resolve, at which point the dose is tapered over 1–2 weeks. Oral antihistamines (e.g., diphenhydramine in standard doses) provide additional relief of symptoms.

Morbidity and Mortality

The overall mortality rates for venomous snakebite are low in areas with rapid access to medical care and appropriate antivenoms. In the United States, for example, the mortality rate is <1% for victims who receive antivenom. Eastern and western diamondback rattlesnakes (Crotalus adamanteus and C. atrox, respectively) are responsible for the few snakebite deaths occurring in the United States. Snakes responsible for large numbers of deaths in other regions include cobras (Naja spp.), carpet and saw-scaled vipers (Echis spp.), Russell's vipers (D. russelii), large African vipers (Bitis spp.), lancehead pit vipers (Bothrops spp.), and tropical rattlesnakes (C. durissus).

The incidence of morbidity—defined as permanent functional loss in a bitten extremity—is difficult to estimate but is substantial. Morbidity may be due to muscle, nerve, or vascular injury or to scar contracture. In the United States, such loss tends to be more common and severe after rattlesnake bites than after bites by copperheads (Agkistrodon contortrix) or water moccasins (A. piscivorus).

Eye Anatomy

A Brief Anatomy of the Eye
Gray's Anatomy 39th

The eyeball, the peripheral organ of vision, is situated in a skeletal cavity, the orbit, the walls of which help to protect it from injury. The orbit also has a more fundamental role in the visual process itself, in providing a rigid support and direction to the eye and in forming the sites of attachment for its external muscles. This setting permits the accurate positioning of the visual axis under neuromuscular control, and determines the spatial relationship between the two eyes - essential for binocular vision and conjugate eye movements.

The eyeball is embedded in orbital fat, separated from it by a thin fascial sheath. It is composed of the segments of two spheres of different radii. The anterior segment, part of the smaller sphere, is transparent and forms c.7% of the surface of the whole globe. It is more prominent than the posterior segment, which is part of a larger sphere and opaque, and forms the remainder of the globe. The anterior segment is bounded by the cornea and the lens, and is incompletely subdivided into anterior and posterior chambers by the iris. These chambers are continuous through the pupil. The anterior chamber is slightly overlapped by the sclera peripherally. The angle between the iris and cornea therefore forms an annulus of greater diameter than the limbus, the junction between the sclera and cornea. The difference between these two varies from 1 to 2 mm, the angle being deeper above and below than at the sides of the eyeball. The posterior chamber lies between the posterior surface of the iris and the anterior aspect of the lens and its supporting ligament, the zonule, and is triangular in section. The apex of the triangle is the point where the iris touches the lens, and the base, or zonular region, extends among the collagenous bundles of the zonule, sometimes even into a retrozonular space between the zonule and the vitreous humour in the posterior segment of the eyeball. The posterior segment consists of the parts of the eye posterior to the zonule and lens.

The anterior pole is the centre of the anterior (corneal) curvature, and the posterior pole is the centre of its posterior (scleral) curvature; a line joining these two points forms the optic axis. (By the same convention, the eye has an equator, equidistant between the poles: any circumferential line joining the poles is a meridian.) The optic axes of the two eyes, in their primary position, are parallel and do not correspond with the orbital axes, which diverge anterolaterally at a marked angle to each other . The optic nerves follow the orbital axes and are therefore not parallel; each enters its eye c.3 mm medial (nasal) to the posterior pole. The ocular vertical diameter (23.5 mm) is rather less than the transverse and anteroposterior diameters (24 mm); the anteroposterior diameter at birth is c.17.5 mm and at puberty 20-21 mm; it may vary considerably in myopia (c.29 mm) and in hypermetropia (c.20 mm). In females all diameters are on average slightly less than in the male.

Figure 1 The organization of the eye, viewed from above. In this illustration the left eye and part of the lower eyelid are depicted in horizontal section and also cut away to show internal structure.

OCULAR FIBROUS TISSUE

The eye has three layers enclosing its contents. From the outer surface these are a fibrous layer, which consists of the sclera behind and the cornea in front; a vascular, pigmented layer which consists of (from behind forwards) the choroid, ciliary body and iris, collectively termed the uveal tract; and a neural layer, known as the retina.

The fibrous layer of the eyeball (Fig. 1) has an opaque posterior sclera and a transparent anterior cornea. Together these form the protective enclosing capsule of the eye, a semi-elastic structure which when made turgid by intraocular pressure, determines with great precision the optical geometry of the visual apparatus. The sclera also provides attachments for the extraocular muscles which rotate the eye, its smooth external surface rotating easily on the adjacent tissues of the orbit. The cornea admits light, refracts it towards a retinal focus, and plays an important role in the image-processing mechanism

OCULAR VASCULAR TUNIC

The vascular tunic, or uveal tract (Fig. 2), consists of the choroid, ciliary body and iris (Fig. 3), which collectively form a continuous structure. The choroid covers the internal scleral surface, and extends forwards to the ora serrata. The ciliary body continues forward from the choroid to the circumference of the iris, which is a circular diaphragm behind the cornea and in front of the lens. It presents an almost central aperture, the pupil

Figure 2 The vascular arrangements of the uveal tract. The long posterior ciliary arteries, one of which is visible (A), branch at the ora serrata (b) and feed the capillaries of the anterior part of the choroid. Short posterior ciliary arteries (C) divide rapidly to form the posterior part of the choriocapillaris. Anterior ciliary arteries (D) send recurrent branches to the choriocapillaris (e) and anterior rami to the major arterial circle (f). Branches from the circle extend into the iris (g) and to the limbus. Branches of the short posterior ciliary arteries (C) form an anastomotic circle (h) (of Zinn) round the optic disc, and twigs (i) from this join an arterial network on the optic nerve. The vorticose veins (J) are formed by the junctions (k) of suprachoroidal tributaries (l). Smaller tributaries are also shown (m, n). The veins draining the scleral venous sinus (o) join anterior ciliary veins and vorticose tributaries. (By permission from Hogan MJ, Alvarado JA, Weddell JE 1971 Histology of the Human Eye. Philadelphia: WB Saunders.)

Figure 3. Composite view of the surfaces and internal strata of the iris. In a clockwise direction from above, the pupillary (A) and ciliary (B) zones are shown in successive segments. The first (brown iris) shows the anterior border layer and the openings of crypts (c). In the second segment (blue iris), the layer is much less prominent and the trabeculae of the stroma are more visible. The third segment shows the iridial vessels, including the major arterial circle (e) and the incomplete minor arterial circle (f). The fourth segment shows the muscle stratum, including the sphincter (g) and dilator (h) of the pupil. The everted 'pupillary ruff' of the epithelium on the posterior aspect of the iris (d) appears in all segments. The final segment, folded over for pictorial purposes, depicts this aspect of the iris, showing radial folds (i and j) and the adjoining ciliary processes (k). (By permission from Hogan MJ, Alvarado JA, Weddell JE 1971 Histology of the Human Eye. Philadelphia: WB Saunders.)

RETINA

The retina is the sensory neural layer of the eyeball. It is a most complex structure and should be considered as a special area of the brain, from which it is derived by outgrowth from the diencephalon . It is dedicated to the detection and early analysis of visual information and is an integrated part of the much larger apparatus of visual analysis present in the thalamus, cortex and other areas of the central nervous system.

Layers of Retina

The retina is organized into layers or zones where distinctive components of its cells are clustered together or in register to form continuous strata. These layers extend uninterrupted throughout the photoreceptive retina except at the exit point of the optic nerve fibres at the optic disc, although certain layers are much reduced at the foveola where the photoreceptive elements predominate. The names given to the different layers reflect in part the components present within them, and also their position in the thickness of the retina. Conventionally, those structures furthest from the vitreous (i.e. towards the choroid) are designated as outer or external, and those towards the vitreous are inner or internal.

Customarily, ten retinal layers are distinguished (Fig. 4), beginning at the choroidal edge and passing towards the vitreous. These are: retinal pigment epithelium; layer of rods and cones (outer segments and inner segments); external limiting membrane; outer nuclear layer; outer plexiform layer (OPL); inner nuclear layer (INL); inner plexiform layer (IPL); ganglion cell layer; nerve fibre layer; internal limiting membrane. Some of these are subdivisible into substrata, and an innermost plexiform layer between layers 8 and 9 has also been demonstrated.


The composition of the different retinal layers is as follows:

Layer 1: Pigment epithelium

This is a simple low cuboidal epithelium which forms the back of the retina, and, therefore forms the boundary with the choroid, from which it is separated by a thick composite basal lamina.

Layer 2: Rod and cone cell processes

This contains the photoreceptive outer segments and the outer part of the inner segments of rod and cone cells.

Layer 3: External limiting membrane

This layer appears as a distinct line by light microscopy. It consists of a zone of intercellular junctions of the zonula adherens type (p. 7) between the processes of radial glial cells and photoreceptor processes.

Layer 4: Outer nuclear layer

This consists of several tiers of rod and cone cell bodies and their nuclei, the cone nuclei lying outermost. Mingled with these are the outer and inner fibres from the same cell bodies, directed outward to the bases of inner segments, and inwards towards the outer plexiform layer.

Layer 5: Outer plexiform layer

This is a region of complex synaptic arrangements between the processes of the cells whose cell bodies lie in the adjacent layers. The outer plexiform layer contains the synaptic processes of rod and cone cells, bipolar cells, horizontal cells, and some interplexiform cells (which in this account are grouped with the amacrines).

Layer 6: Inner nuclear layer

This is composed of three nuclear strata. Horizontal cell nuclei form the outermost zone, then in sequence inwards, the nuclei and cell bodies of bipolar cells, radial glial cells, and the outer set of amacrine cells, including the interplexiform cells whose dendrites cross this layer.

Layer 7: Inner plexiform layer

This is divisible into three layers depending on the types of contact occurring. The outer or 'OFF' layer contains synapses between 'OFF' bipolar cells, ganglion cells and some amacrines; a middle or 'ON' layer contains synapses between the axons of 'ON' bipolars and the dendrites of ganglion cells and displaced amacrines; and an inner 'rod' layer contains synapses between rod bipolars and displaced amacrines. (Refer to Wässle & Boycott 1991 for an explanation of the 'OFF' and 'ON' cell designations.)

Layer 8: Ganglion cell layer
This layer contains the nuclei of the displaced amacrine cells. Its inner regions consist of the cell bodies, nuclei and initial segments of retinal ganglion cells of various classes.

Layer 9: Nerve fibre layer

This contains the unmyelinated axons of retinal ganglion cells. It forms a zone of variable thickness over the inner retinal surface, and is the only component of the retina at the point where the fibres pass into the nerve at the optic disc. The inner aspect of this layer contains the nuclei and processes of astrocytes which, together with radial glial cells, ensheath the nerve fibres. Between the nerve fibre layer and the ganglion cells there is another narrow innermost plexiform layer where neuronal processes make synaptic contact with the axon hillocks and initial segments of ganglion cells.

Layer 10: Internal limiting membrane

This is a glial boundary between the retina and the vitreous body. It is formed by the end feet of radial glial cells and astrocytes, and is separated from the vitreous body by a basal lamina.

Figure 4 The layered arrangement of neuronal cell bodies in the retina and the interconnections of their processes in the intervening plexiform layers. Also shown are the two principal types of neuroglial cell in the retina; microglia are also present but not shown.

Optic disc

The optic disc is the region where retinal tissues meet the neural and glial elements of the optic nerve and the connective tissues of the sclera and meninges. It is the exit point for the optic nerve fibres, and a point of entry and exit for the retinal circulation. It is the only site where anastomoses occur with other arteries (the posterior ciliary arteries). It is visible, by ophthalmoscopy, and is a region of much clinical importance, since it is here that the central vessels can be inspected directly: the only vessels so accessible in the whole body. Oedema of the disc (papilloedema) may be the first sign of raised intracranial pressure, which is transmitted into the subarachnoid space around the optic nerve and compresses the central retinal vein where it crosses the space.

The optic disc is superomedial to the posterior pole of the eye, and so lies away from the visual axis. It is round or oval, usually c.1.6 mm in transverse diameter and 1.8 mm in vertical diameter, and its appearance is very variable (for details see Jonas et al 1988). In light-skinned subjects, the general retinal hue is a bright terracotta-red, with which the pale pink of the disc contrasts sharply; its central part is usually even paler and may be light grey. These differences are due in part to the degree of vascularization of the two regions, which is much less at the optic disc, and also to the total absence of choroidal or retinal pigment cells, since the retina is represented in the disc by little more than the internal limiting membrane. In subjects with strongly melanized skins, both retina and disc are darker . The optic disc does not project at all in many eyes, and rarely does it project sufficiently to justify the term papilla. It is usually a little elevated on its lateral side, where the papillomacular nerve fibres turn into the optic nerve. There is usually a slight depression where the retinal vessels traverse its centre.

RETINAL VASCULAR SUPPLY

The central retinal artery enters the optic nerve as a branch of the ophthalmic artery, c.1.2 cm behind the eyeball. It travels in the optic nerve to its head, where its fascicles traverse the lamina cribrosa. At this level, which is usually not visible to ophthalmoscopy, the central artery divides into two equal branches, superior and inferior. After a few millimetres, these divide into superior and inferior nasal, and superior and inferior temporal, branches. Each of these four supplies its own 'quadrant' of the retina, although each territory is much more than a quadrant, since the branches ramify as far as the ora serrata. Corresponding retinal veins unite to form the central retinal vein. However, the courses of the venous and arterial vessels do not correspond exactly, and arteries often cross veins, usually lying superficial to them. In severe hypertension the arteries may press on the veins and cause visible dilations distal to these crossings. Arterial pulsation is not visible by routine ophthalmoscopy without higher magnification.

The branching of the artery is usually dichotomous, and equal rami diverge at angles of 45-60°. Smaller branches may leave singly and at right angles. Arteries and veins ramify in the nerve fibre layer, near the internal limiting membrane, which accounts for their clarity when seen through an ophthalmoscope . Arterioles pass deeper into the retina and may penetrate to the internal nuclear lamina, from which venules return to larger superficial veins. The question of whether or not the dense capillary bed is diffusely organized or layered is unsettled. Some lamination has been identified, most noticeably at the interface between the inner nuclear and outer plexiform layers. The structure of the blood vessels resembles that of vessels elsewhere, except that the internal elastic lamina is absent from the arteries, and muscle cells may appear in their adventitia. Capillaries have a non-fenestrated endothelium.

OCULAR REFRACTIVE MEDIA

The components of the eye that transmit and refract light are the cornea, the aqueous humour, the lens and the vitreous body. Of these, only the refracting power of the lens can be varied.

Aqueous humour

To satisfy the requirements of vision the eye has its own circulatory system. Aqueous humour is secreted into the posterior chamber by the non-pigmented epithelium of the ciliary processes. It passes into the anterior chamber through the pupil and drains to the scleral venous sinus at the iridocorneal angle through the spaces of the trabecular tissue. It is responsible for maintaining the metabolism of the avascular transparent media, vitreous, lens and cornea, and it also maintains and regulates the relatively high intraocular pressure (c.17 mmHg), and hence the constancy of the ocular dimensions of the eyeball, via the balance between production and drainage. Depth of the anterior chamber may be assessed using slit-lamp biomicroscopy, and the filtration angle may be viewed directly by gonioscopy. Any interference with its drainage into the sinus increases intraocular pressure leading to the condition of glaucoma.

Lens

The lens is a transparent, encapsulated, biconvex body, which lies between the iris and the vitreous body. Posteriorly, the lens contacts the hyaloid fossa (p. 719) of the vitreous body. Anteriorly, it forms a ring of contact with the free border of the iris, but further away from the axis of the lens the gap between the two increases to form the posterior chamber of the eye (p. 708). The lens is encircled by the ciliary processes, and is attached to them by the zonular fibres which issue mainly from the pars plana of the ciliary body. Collectively, the fibres form the zonule which holds the lens in place and transmits the forces which stretch the lens (except in visual accommodation).

The lens has a characteristic shape. Its anterior convexity is less steep, and has a greater radius of curvature, than the posterior, which has a more parabolic shape. The central points of these surfaces are the anterior and posterior poles; a line connecting these is the axis of the lens. The marginal circumference of the lens is its equator. In fetuses the lens is nearly spherical, has a slight reddish tinge, and is soft, such that it breaks up on application of the slightest pressure. A hyaloid artery from the central retinal artery traverses the vitreous body to the posterior pole of the lens, whence its branches spread as a plexus. This covers the posterior surface and is continuous round the capsular circumference with the vessels of the pupillary membrane and iris.

In infants and adults the lens is avascular, colourless and transparent, but still quite soft in texture. In old age, the anterior surface becomes a little more curved, which pushes the iris forward slightly. It becomes less clear, with an amber tinge, and its nucleus is denser. In cataract, the lens gradually becomes opaque, causing blindness.

The dimensions of the lens are optically and clinically important, but they change with age as a consequence of continuous growth. Its equatorial diameter at birth is 6.5 mm, increasing rapidly at first, then more slowly to 9.0 mm at 15 years of age, and even more gradually to reach 9.5 mm in the ninth decade. Its axial dimension increases from 3.5-4.0 mm at birth to 4.75-5.0 mm at age 95. The radii of curvature reduce throughout life; the anterior surface shows the greater change as the lens thickens (Brown 1974). Average adult radii of the anterior and posterior surfaces are 10 mm and 6 mm respectively; the reduction during accommodation occurs mainly at the anterior surface.

Vitreous body

The vitreous body fills the vitreous chamber, and occupies about four-fifths of the eyeball. It is hollowed in front as a deep concavity, the hyaloid fossa, which is adapted to the lens. It is colourless, consisting of c.99% water, but not entirely structureless. At its perimeter it has a gel-like consistency (100-300μm thick) and is firmly attached to the surrounding structures of the eye; nearer the centre it has a more liquid zone in the form of long glycosaminoglycan chains, fills the whole vitreous. In addition, the peripheral gel or cortex contains a random loose network of type II collagen fibrils which are occasionally grouped into fibres. The cortex also contains scattered cells, the hyalocytes, which possess the characteristics of mononuclear phagocytes. They are responsible for the production of . Whilst they are normally in a resting state, they have the capacity to be actively phagocytic in inflammatory conditions. Hyalocytes are not present in the cortex bordering the lens. The liquid vitreous is absent at birth, appears first at 4 or 5 years, and increases to occupy half the vitreous space by the seventh decade. The cortex is most dense at the pars plana of the ciliary body adjacent to the ora serrata, where attachment is strongest, and this is often referred to as the base of the vitreous. Here the vitreous is thickened into a mass of radial (zonular) fibres which form the suspensory ligament of the lens

A narrow hyaloid canal runs from the optic nerve head to the central posterior surface of the lens. In the fetus this contains the hyaloid artery which normally disappears about 6 weeks before birth. It persists as a very delicate fibrous structure and is of no functional importance.