1. PHARMACOTHERAPY OF MICROBIAL DISEASES IN THE EYE
DR.KARARA M.W.

2. i. Conjunctivitis
Conjunctivitis is an inflammatory process of the conjunctiva that varies in severity from mild hyperemia to severe purulent discharge.
Common causes of conjunctivitis include viruses, allergies, environmental irritants, contact lenses, and chemicals.
Less common causes include other infectious pathogens, immune-mediated reactions, associated systemic diseases, and tumors of the conjunctiva or eyelid.

3. Conjunctivitis: Microbial causes
More commonly reported infectious agents include
adenovirus and herpes simplex virus, enterovirus, coxsackievirus, measles virus, varicella zoster virus, and vaccinia-variola virus)
bacterial sources (e.g., Neisseria species, Streptococcus pneumoniae, Haemophilus species, S. aureus, Moraxella lacunata, and Chlamydia species).
Rare causes of conjunctivitis include Rickettsia, fungi, and parasites (in both cyst and trophozoite form).

4. Bacterial conjuctivitis: Signs and Symptoms
The infection usually starts in one eye and is spread to the other by the hands.
It also may be spread to other persons.
It usually associated with symptoms of a diffusely reddened eye with purulent or serous discharge accompanied by itching, stinging, or a scratching, and foreign-body sensation.

5. Bacterial conjuctivitis

6. Bacterial conjunctivitis: Etiology
The most common causes of bacterial conjuctivitis are staphylococci, streptococci (particularly S pneumoniae), Haemophilus species, Pseudomonas, and Moraxella.
All may produce a copious purulent discharge.
There is no blurring of vision and only mild discomfort.

7. Antibiotic Rx of Bacterial conjuctivitis
The disease is usually self-limited, lasting about 10–14 days if untreated.
Topical sulfonamide (e.g., sulfacetamide, 10% ophthalmic solution or ointment three times a day) will usually clear the infection in 2–3 days.
Other ophthalmic antibiotic drops or ointments, such as neomycin-polymyxin-B-gramicidin combination and povidone-iodine can also be used.
Although other antimicrobials, such as the ocular quinolones may be used for bacterial conjunctivitis, these agents should be reserved as second-line therapies, because of cost and the potential development of resistance.

8. Other measures in Rx of Bacterial conjuctivitis
Proper management of this infection also includes mechanical cleaning of the eyelids and hygienic measures that prevent spreading the infection to other children.
The deposits should be removed as often as possible with moist cotton swabs or cotton-tipped applicators.
A mild baby shampoo can be used to moisten the applicator.
Firm adherent crusts may be softened with warm, moist compresses.

9. ib. Gonococcal conjunctivitis
Gonococcal conjunctivitis is usually acquired through contact with infected genital secretions,
It typically causes copious purulent discharge
It is an ophthalmologic emergency because corneal involvement may rapidly lead to perforation.
The diagnosis should be confirmed by stained smear and culture of the discharge.

10. ib. Gonococcal conjunctivitis: Rx
A single 1-g dose of intramuscular ceftriaxone is usually adequate.
Topical antibiotics such as erythromycin and bacitracin may be added.
Other sexually transmitted diseases, including chlamydia, syphilis and HIV infection should be considered.

11. Trachoma
Trachoma is a chronic keratoconjunctivitis caused by Chlamydia trachomatis.
It is the world’s leading cause of preventable blindness of infectious origin.

12. Trachoma: Transmission
C trachomatis can be spread by either:
direct contact with an infected person's eyes or nose or
indirect contact, such as through contact with clothing or flies that have come into contact with an infected person's eyes or nose.
Poor sanitation, crowded living conditions, and insufficient clean water and toilets can also increase the spread of trachoma.
Disease transmission occurs primarily between children and the women who care for them.
Flies that transmit trachoma preferentially lay their eggs on human feces lying exposed on soil.

13. Trachoma:Pathophysiology
Repeated episodes of reinfection cause chronic intense conjunctival inflammation (active trachoma), which leads to tarsal conjunctival scarring.
The scarring distorts the upper tarsal plate and, in some individuals, leads to entropion and trichiasis (cicatricial trachoma).
The end result includes corneal abrasions; corneal scarring and opacification; and, ultimately, blindness.

14. Trachoma

15. Trachoma: Prevention and control
Prevention of trachoma-related blindness requires a number of interventions.
The World Health Organization (WHO) and their partners endorse the surgery, antibiotics, facial cleanliness, and environmental improvement (SAFE) strategy for trachoma control

16. SAFE strategy: Surgery
“S”in the SAFE strategy stands for trichiasis surgery.
Eyelid surgery to correct trichiasis is important in people with trichiasis, who are at high-risk for trachomatous visual impairment and blindness.
Eyelid surgery to correct entropion and/or trichiasis may prevent blindness in individuals at immediate risk.

17. SAFE strategy: Antibiotics
The WHO recommends 2 antibiotics for trachoma control:
oral azithromycin
tetracycline eye ointment.
Azithromycin eye drops have also been shown to be very effective.
Azithromycin is better than tetracycline, but it is more expensive.

18. SAFE strategy: Antibiotics (cont’d)
Azithromycin is the drug of choice because it is easy to administer as a single oral dose.
Its administration can be directly observed.
Therefore, compliance is higher than with tetracycline and can actually be measured, whereas, with the home administration of tetracycline, the level of compliance is unknown.
Azithromycin has high efficacy and a low incidence of adverse effects.
When adverse effects occur, they are usually mild; gastrointestinal upset and rash are the most common adverse events.
Infection with C trachomatis occurs in the nasopharynx; therefore, patients may reinfect themselves if only topical antibiotics are used.

19. SAFE strategy: Facial cleanliness
Epidemiologic studies and community-randomized trials have shown that facial cleanliness in children reduces both the risk and the severity of active trachoma.
To be successful, health education and promotion activities must be community based and require considerable effort.

20. SAFE strategy: Environmental improvement
General improvements in personal and community hygiene are almost universally associated with a reduction in the prevalence—and eventually the disappearance—of trachoma.
Environmental improvement activities include
the promotion of improved water supplies and
improved household sanitation, particularly methods for safe disposal of human feces.

21. iii. Dacryoadenitis
Dacryoadenitis is an infection of the lacrimal gland located at the outer upper eyelid.
It is most common in children and young adults.
Dacryoadenitis is most commonly due to inflammation, and occurs in conditions such as sarcoidosis.
It may be bacterial (typically Staphylococcus aureus, Streptococcus species) or viral (most commonly seen in mumps, infectious mononucleosis, influenza, and herpes zoster).

22. Dacryoadenitis: Signs and symptoms
It is characterized by pain, redness, swelling, tearing, and discharge over the lacrimal gland (ie, the lateral one-third of the upper eyelid).
Other common signs are fever, and an elevated white blood cell count.
Any discharge from the lacrimal sac should be sent for smears and cultures.
Systemic antibiotics typically are indicated.

23. Dacryoadenitis

24. Dacryoadenitis: Rx
Dacryoadenitis is empirically treated with systemic antibiotics until the exact cause is identified.
These include amoxicillin-clavulanate, cefuroxime, cephalexin and cefazolin
Inflammatory causes are treated with 80 to 100 mg of oral prednisone once daily, along with an antiulcer medication, such as 150 mg of oral ranitidine twice daily.
Viral causes are treated for symptom relief, including cool compresses over the affected area and over-the-counter analgesics.

25. iv. Hordeolum (stye )
A hordeolum, is an infection of the meibomian, Zeis, or Moll glands at the eyelid margins.
It is typically caused by S. aureus,
Meibomian, Zeis and Moll glands Glands of Zeis are sebaceous glands located on the margin of the eyelid. These glands produce an secrete lipids that adds to the superficial layer of the tear film, thus preventing evaporation of tears.

26. Hordeolum (stye )

27. Hordeolum: Rx Medical therapy for hordeola includes:
Eyelid hygiene (lid scrubs),
Warm compresses and massages of the lesions for 10 minutes 4 times per day,
Topical antibiotic ointment can be used if the lesion is draining
Systemic antibiotics may be indicated if the hordeola is complicated by preseptal cellulitis. 
Co-amoxiclav, cephalexin, erythromycin can be used

28. iv. Blepharitis
Blepharitis refers to inflammation of the eyelid margins;
It is usually associated with Staphylococcus spp.
Patients with blepharitis typically present with symptoms of eye irritation, itching, erythema of the lids, flaking of the lid margins, and/or changes in the eyelashes.
Blepharitis primarily affects older persons (mean age years)

30. Blepharitis: Rx Eyelid hygiene is the mainstay of therapy.
Topical antibiotics frequently are used, usually in ointment form, particularly when the disease is accompanied by conjunctivitis and keratitis.
Refractory cases of blepharitis often respond to oral antibiotic use.
Systemic tetracycline, doxycycline, minocycline, and erythromycin often are effective in reducing severe eyelid inflammation, but must be used for 4-8 weeks .

31. Blepharitis : Eyelid hygiene
Step
Description 1
Soaked warm compresses are applied to the lids repeatedly to warm the eyelid gland secretions, to liquiefy the turbid lipid glandular material and to promote evacuation and cleansing of the secretory passages. Patients should be instructed to use extreme care and to avoid the use of excessive heat. 2
The eyelid margin is washed mechanically to remove adherent material such as crusts and to clean the gland orifices. This can be completed with a warm washcloth or with cotton-tip applicators or gauze pads. Water can used but some clinicians prefer that a few drops of baby shampoo be mixed in one bottle cap full of warm water to form a cleaning solution. Attention must be directed to gentle mechanical scrubbing of the eyelid margin itself, not the skin of the lids or of theconjunctival surface. Vigorous scrubbing is not necessary and may be harmful. 3
An antibiotic ointment is applied to the eyelid margin after it has been soaked and scrubbed. Commonly used agents include bacitracin, polymyxin B, erythromycin, or sulfacetamide ointments. Antibiotic-corticosteroid ointment combinations can be used for short courses, although, because of the risks associated with ocular steroids, their use is less appropriate for long-term management.

32. V. Keratitis
Keratitis, or corneal inflammation can be due to noninfectious or infectious causes.
Microbial causes of infectious keratitis, include bacteria, viruses, fungi, spirochetes, and cysts and trophozoites.

33. Keratitis

34. Keratitis: General Rx guidelines
Severe infections, with tissue loss (corneal ulcers), generally are treated more aggressively than infections without tissue loss (corneal infiltrates).
Mild, small, more peripheral infections usually are not cultured and the eyes are treated with broad spectrum topical antibiotics.
In more severe, central, or larger infections, corneal scrapings for smears, cultures, and sensitivities are performed and the patient is immediately started on intensive hourly, around-the-clock topical antibiotic therapy.

35. Va: Bacterial keratitis
Bacterial keratitis is a sight-threatening process.
Bacterial keratitis remains one of the most important potential complications of contact lens use and refractive corneal surgery. 
A particular feature of bacterial keratitis is its rapid progression;
Corneal destruction may be complete in hours with some of the more virulent bacteria.
Corneal ulceration, stromal abscess formation, surrounding corneal edema, and anterior segment inflammation are characteristic of this disease.

36. Bacterial keratitis: Rx
The initial choice of therapy for bacterial corneal ulcers commonly is based on a Gram's stain and clinical impression of the severity of the ulcer.
If no organisms are identified on the slide smear, initiate broad-spectrum antibiotics with the following: tobramycin (14 mg/mL) 1 drop every hour alternating with fortified cefazolin (50 mg/mL) 1 drop every hour.
If the corneal ulcer is small, peripheral and no impending perforation is present, intensive monotherapy with fluoroquinolones is an alternative treatment.
Other antimicrobials can be used, depending on the clinical progress and laboratory findings.
Although commercial antimicrobial ophthalmic formulations are available, the antimicrobial concentrations in these products might be inadequate to effectively treat bacterial corneal ulcers.
Topical antimicrobials for the treatment of bacterial corneal ulcers can be prepared from parenteral antimicrobials or by the addition of parenteral antimicrobials to “fortify” commercially available products.
Commonly prescribed products include bacitracin 5,000 to 10,000 U/mL, cefazolin 33 to 100 mg/mL, gentamicin or tobramycin 9.1 to 13.6 mg/mL, and vancomycin 25 to 50 mg/mL.
Fortified gentamicin has been prepared by adding 80 mg of parenteral gentamicin to the commercially available gentamicin ophthalmic solution. The final concentration of this solution is 13.6 mg/mL.
Cefazolin ophthalmic solution is prepared by reconstituting 500 mg parenteral cefazolin with 2 mL sterile normal saline. Two milliliters of artificial tears solution are removed from a commercially available 15-mL bottle and replaced with the 2-mL reconstituted cefazolin solution (resulting in a final cefazolin concentration of 33 mg/mL). Therapy initially can be administered as frequently as every 15 to 30 minutes with extension of intervals as the ulcer resolves

37. Vb. Viral keratitis
Viral keratitis, an infection of the cornea that may involve either the epithelium or stroma, is most commonly caused by herpes simplex type I and varicella zoster viruses.
Less common viral etiologies include herpes simplex type II, Epstein-Barr virus, and cytomegalovirus.
Topical antiviral agents are indicated for the treatment of epithelial disease due to herpes simplex infection.

38. Viral keratitis: Rx
When treating viral keratitis topically, there is a very narrow margin between the therapeutic topical antiviral activity and the toxic effect on the cornea; hence, patients must be followed very closely.
Topical glucocorticoids are contraindicated in herpetic epithelial keratitis due to active viral replication. In contrast, for herpetic disciform keratitis, which is presumed to predominantly involve a cell-mediated immune reaction, topical glucocorticoids accelerate recovery.
For recurrent herpetic stromal keratitis, there is clear benefit from treatment with oral acyclovir in reducing the risk of recurrence.

39. Vc. Acanthamoeba keratitis
Acanthamoeba keratitis is a parasitic infection which is very common in persons wearing contact lenses
Risk factors include:
Poor contact lens hygiene,
Ocular trauma.
Treatment usually consists of a combination topical antibiotic, such as polymyxin B sulfate, bacitracin zinc, and neomycin sulfate.
Sometimes an imidazole (e.g., clotrimazole, miconazole, or ketoconazole) can be included in the treatment.

40. Acanthamoeba keratitis
Other treatments include:
The use of the aromatic diamidines i.e. propamidine isethionate in both topical aqueous and ointment forms.
The cationic antiseptic agent polyhexamethylene biguanide (PHMB) which is typically used in drop form
Topical chlorhexidine is an alternative to PHMB.
Oral itraconazole or ketoconazole often are used in addition to the topical medications
Resolution of Acanthamoeba keratitis may require many months of treatment.

41. vi. Endophthalmitis
Endophthalmitis is an inflammatory condition of the intraocular cavities (ie, the aqueous and/or vitreous humor) usually caused by infection.
Endophthalmitis is usually caused by bacteria or fungi, or rarely by spirochetes.
The typical case occurs during the early postoperative course (e.g., after cataract, glaucoma, cornea, or retinal surgery), following trauma, or by endogenous seeding in the immunocompromised host .
Noninfectious (sterile) endophthalmitis may result from various causes such as retained native lens material after an operation or from toxic agents.
Panophthalmitis is inflammation of all coats of the eye including intraocular structures.

43. Endophthalmitis: Rx Type Rx Postoperative endophthalmitis
Vitrectomy or vitreous aspiration may be performed by an ophthalmologist with administration of intravitreal antibiotics (ie, vancomycin, amikacin, ceftazidime).
Consider systemic antibiotic administration as well as intravitreal steroids.
Traumatic endophthalmitis
Admit to hospital. Systemic antibiotics including vancomycin and an aminoglycoside or a third-generation cephalosporin are indicated. Consider clindamycin until Bacillus species can be ruled out if soil contamination is suspected.Topical fortified antibiotics are used.Intravitreal antibiotics should be administered.Tetanus immunization is necessary if immunization record is not current.Cycloplegic drops (ie, atropine) may be considered.
Endogenous bacterial endophthalmitis
Broad-spectrum intravenous antibiotics including vancomycin and an aminoglycoside or third-generation cephalosporin. Consider adding clindamycin in intravenous drug users until Bacillus infection can be ruled out.Periocular antibiotics are sometimes indicated.Intravitreal antibiotics are indicated.
Cycloplegic drops (ie, atropine) may be administered.Topical steroids may be considered.Vitrectomy may be needed for virulent organisms.
Candidal endophthalmitis
Admit the patient to the hospital.Oral fluconazole is indicated.Amphotericin B intravenous or intravitreal may be considered.Cycloplegic drops (ie, atropine) may be considered.

44. vii. Herpes zoster ophthalmicus
Herpes zoster ophthalmicus is a latent reactivation of a varicella zoster infection in the first division of the trigeminal cranial nerve.
Systemic acyclovir, valacyclovir, and famciclovir are effective in reducing the severity and complications of herpes zoster ophthalmicus.

45. viii. Viral retinitis
Viral retinitis may be caused by herpes simplex virus, cytomegalovirus (CMV), adenovirus, and varicella zoster virus.
With the highly active antiretroviral therapy, CMV retinitis does not appear to progress when specific anti-CMV therapy is discontinued, but some patients develop an immune recovery uveitis.
Treatment usually involves long-term parenteral administration of antiviral drugs.
Intravitreal administration of ganciclovir has been found to be an effective alternative to the systemic route.

46. ix. Retinal necrosis
Acute retinal necrosis and progressive outer retinal necrosis, most often caused by varicella zoster virus, can be treated by various combinations of oral, intravenous, intravitreal injection, and intravitreal implantation of antiviral medications.

47. x. Toxoplasmosis
Toxoplasmosis may present as a posterior (e.g., focal retinochoroiditis, vitritis, or retinitis) or occasionally as an anterior uveitis.
Treatment is indicated when inflammatory lesions encroach upon the macula and threaten central visual acuity.

48. Toxoplasmosis: Rx
Several regimens have been recommended with concurrent use of systemic steroids:
Pyrimethamine , sulfadiazine, and folinic acid (leucovorin);
Pyrimethamine, sulfadiazine, clindamycin, and folinic acid;
Sulfadiazine and clindamycin;
Clindamycin ;
Trimethoprim -sulfamethoxazole with or without clindamycin.