EXTERNAL DISEASE AND CORNEA

Embryology
-
week 4 of gestation, neuroectoderm evagination
-
week 5 of gestation, optic vesicle invagination to form optic cup
-
surface ectoderm: lens placode and corneal, conjunctival epithelium, eyelid
epidemis
-
mesenchymal cells from the neural crest of surface ectoderm: corneal
endothelium
-
week 6 of gestation, mesenchymal cells of neural crest: corneal stroma and
sclera

-
at 3 mos, all corneal components are present except bowman’s layer (4th mo)
-
at 6 mos, eyelids begin to open
-
at birth, infant’s globe is 80% of adult size; pupillary membrane has regressed
cornea is 9.5-10.5mm in diameter; adult size at 2y/o; sclera more rigid at 2 years
of age
-
tear reflex is absent until 3 weeks after birth and gland continues to grow for 3-
4 years

Anatomy
-
cilia are replaced every 3-5 mos; regrow in 2 weeks when cut and within 2 mos
if pulled out
-
eyelid margin, apocrine sweat glands (glands of Moll) and sebaceous glands
(glands of Zeis)
-
palisades of Vogt: contains corneal stem cells at the limbus
-
Cornea: 11-12 mm horizontally and 10-11mm vertically; refractive index 1.376,
aspheric; average radius 7.8mm; contributes 74% or 43.25 D of total 58.60D of
normal human eye; one of the body’s highest densities of nerve endings (long
ciliary nerves)
-
Corneal Transparency: Avascular
Nonkeratinized
Paucity of cells
Relative deturgescence (endothelial pump) 78% water
content
Uniform arrangement of collagen fibrils
-
major corneal proteoglycans: decorin (associated w/ dermatan sulfate) &
lumican (keratin sulfate)
sclera: dermatan sulfate
Examination
-
Specular reflection: endothelial mosaic; guttae and KP’s
-
Sclerotic scatter: epithelial edema and nebulae
-
Retroillumination: subtle corneal abnormalities
-
Fluorescein: disruption of intracellular junctions
-
Rose bengal: devitalized cells that have lost their normal mucin surface
-
Papillae (vascular changes): Bacterial and Allergic conjunctivitis; Soft contact
lens wearer; SJS
-
Follicles(lymphoid): Chlamydia, HSV, Adenoviral, Molluscom, Pharmacologic
(dipivefrin)
-
Membrane/Pseudomembrane: Severe conjunctivitis, SJS, chemical burn (Sunog)
-
Key feature of stromal inflammation is presence of new blood vessels
-
Pseudoguttae: swollen endothelial cells
-
Keratic precipitates: clumps of inflammatory cells on the endothelium
-
Pannus: subepithelial fibrous ingrowth into the peripheral cornea
 -
Scleromalacia: areas of increased transluscency
-
Pachymetry: corneal thickness; thinnest zone is about 1.5mm temporal to the
geographic center
-
DM folds: CCT increases by 10%; epithelial edema: CCT>0.70mm (normal
0.52mm); increased permeability and insufficient pump when endothelial cell
density is lower than 500 cells/mm2
-
Early signs of corneal edema: Patchy or diffuse haze of the epithelium
Mild stromal thickening
Waite-Beetham lines: faint deep stromal wrinkles
DM folds, pseudoguttae and corneal guttae
-
Endothelial cells: children >3500cells/mm2
Adults: 2400 cells/mm2 (1500-3500) ↓ to 2000 in older eyes
mean cell size 150-350 μm2
Donor corneas: 2000 cells/mm2
-
Polymegathism: increased variation in individual cell areas (>0.40) seen in
contact lens wear
-
Pleomorphism: increased variability in cell shape (>50% nonhexagonal)
-
Keratinized epithelial cells: OCP, SJS, severe KCS and graft versus host disease
-
Keratometry: estimates corneal power by reading 4 points of the central 2.8-
4.0mm zone
Tear Film
pH 7.2 thickness: 8-9 μm
osmolarity: 302 mOsm/L refractive index 1.336
volume: 7.0 μL rate: 1.2 μL/min
K+ is 5-7X greater than that in serum while Na+ parallels that of the serum
Urea, glucose, ascorbate, citrate, lactate, amino acids, protein like IgA, IgM, IgG
and IgE

Layers: Lipid: meibomian glands (MGD)

Aqueous: main and accessory lacrimal glands (ATD)
Mucin: conjunctival goblet cells and ocular surface epithelium (chemical burn –
xerosis)

Examination
-
TBUT: instability and rupture of the mucin layer by van der Waals forces
(<10secs is abnormal)
-
Tear meniscus: normally 1.0mm in height and convex (0.3 or less is abnormal)
-
Basic secretion test: with anesthesia for 5 mins (≥10 mm)
-
Schirmer I: without anesthesia for 5 mins (≥10 mm)
-
Schirmer II: without anesthesia for 5 mins but with nasal stimulation (≥15 mm)
-
Gram stain: (VIAS) crystal Violet (1min) grams Iodine (1min) Alcohol; Safranin (1
min)
-
Giemsa stain: Giemsa stain (1hr); Ethanol – Chlamydial inclusions purple red
Bacteria and fungi blue purple
-
Acridine orange stain: acidic acridine orange dye (2mins) – Bacteria and
amoeba orange
Tissue cells and fungi green
-
Calcofluor white stain: calcofluor white-Evans blue stain – Fungi and amebic
cyst green
-
Acid-fast stain: Carbofuschin (5mins); Acid alcohol; Malachite green (5mins)
Most Mycobacterium and Nocardia stain
red
-
PAS stain: mucin content of goblet cells stains magenta
-
Halberstaedter-Prowazek inclusion bodies: neonatal chlamydial conjunctivitis
 -
Lipschutz bodies: Cowdry type I intranuclear inclusion bodies seen in HSV and
VZV

Meibomian Gland Dysfunction

-
lipid tear deficiency which results in tear film instability, increased rate of tear
film evaporation and elevated tear osmolarity; risk factors include rosacea and
oral retinoid therapy
-
with prominent telangiectatic blood vessels (brush marks), papillary reaction,
punctate epithelial erosions, marginal infiltrates, pannus and corneal thinning
-
Treatment: Lid scrub, warm compress
Systemic Tetracycline 250mg q6hrs for 3-4 wks tapered to 250-500
mg daily
Doxycycline 100 mg q12hrs for 3-4 wks tapered to 50-100 mg daily
Minocycline 50 mg q12hrs for 3-4 wks then tapered
Erythromycin

Chalazion
-
localized lipogranulomatous inflammation involving the meibomian or gland of
Zeis
-
granulomas: epithelioid cells are prominent with lymphocytes, macrophage,
neutrophil, plasma cells and giant cells
-
internal chalazia: vertical incisions (avoid horizontal scarring of the tarsal plate)
-
recurrent chalazia: rule out meibomian gland carcinoma

Sarcoidosis
-
non-caseating granulomas in affected tissues (eyelid skin, conjunctiva, lacrimal
gland)
-
Mikulicz syndrome: concomitant enlargement of the lacrimal and salivary
glands combined with keratoconjunctivitis sicca
-
Lofgren syndrome: erythema nodosum, hilar adenopathy and iridocyclitis
-
Heerdordts syndrome: with uveitis, fever and facial nerve palsy (uveoparotid
fever)
-
Calcific band keratopathy is the most common corneal finding
-
Granulomatous uveitis with mutton-fat keratic precipitates and iris nodules
-
Periphlebitis is the most common fundus finding

Dry Eye Syndrome

-
disorder of tear film which results from either ↓ tear production or excessive
tear evaporation
-
Global symptoms: ↓ tear film; ocular surface damage, hyperosmolarity and
inflammation of ocular surface and tear producing glands
-
Symptoms tend to be worse toward the end of the day, with prolonged use of
the eye and with exposure to environmental extremes
-
Fluorescein, Rose bengal and Lissamine green stain: nasal and temporal limbus
or inferior paracentral cornea (exposure staining); inferior cornea and
conjunctiva (linear staining)
-
Vitamin A deficiency is the most common cause of mucin deficiency: corneal &
conjunctival xerosis, bitot spots, xerophthalmia, nyctalopia - earliest symptom,
corneal ulceration, and keratomalacia
-
Treatment: topical tear substitute, cyclosporine, acetylcysteine, punctual plugs,
tarsorrhaphy

Sjogren Syndrome
 -
Ocular symptom: dry eyes x >3mos, sensation of sand or gravel and use of tear
substitute >TID
-
Oral symptom: dry mouth x >3mos, swollen salivary glands & difficulty
swallowing dry foods
-
Ocular signs: Schirmer I (=5mm in 5 mins) and Rose bengal score ( =4
Bijsterveld score)
-
Histopath: Focus score = 1 on minor salivary gland biopsy
-
Salivary gland involvement: salivary scintography, parotid sialography,
unstimulated salivary flow
-
Autoantibodies: Ab to Ro/SS-A or La/SS-B antigens, ANA and RF

Neurotrophic Keratopathy
-
results from damage of CNV causing corneal hypoesthesia and anesthesia
-
surgical trauma, CVA, aneurysm, MS, tumors, VZV, HSV, Hansen (leprosy),
topical anesthetic abuse, Riley Day syndrome and hereditary sensory
neuropathy
-
epithelial defects stain intensely with fluorescein and surrounded by raised
rolled-up gray edges

Exposure Keratitis: result from any disease that limits eyelid closure (lagophthalmos)
Floppy eyelid Syndrome: flimsy, lax upper tarsus that everts with minimal upward force
to the upper eyelid
Superior Limbic Keratoconjunctivitis: mechanical trauma transmitted from the upper
eyelid to the superior bulbar and tarsal conjunctiva; papillary rxn;
characateristic nuclear pyknosis with “snake nuclei” and loss of goblet cells;
associated with thyroid disease
Recurrent Corneal Erosion: poor adhesion of the epithelium caused by abnormality in
the epithelial basement membrane
Dellen: saucer-like depression due to desiccation of the epithelium and subepithelial
tissues at or near the limbus adjacent to surface elevation produced by
pterygium, large filtration blebs and dermoids

Contact Lens Wear

-
Sattler’s veil: central epithelial edema (hypoxia w/ lactate accumulation &
impaired CO2 efflux)
-
Microcystic epitheliopathy seen with retroillumination; extended-wear soft
contect lenses
-
Toxic conjunctivitis: cleaning agents such as benzalkonium Cl. Chlorhexidine,
hydrogen peroxide
-
Allergic reaction: preservative thimerosal (delayed hypearsensitivity)
-
Neovascularization: superficial pannus with soft CL; deep stromal NV with
extended wear CL

Limbal Stem Cell Deficiency

-
Corneal stem cells are located in the basal cell layer of the limbus whereas
conjunctival stem cells are uniformly distributed throughout the bulbar surface
-
Approximately 25-33% of the limbus must be intact in order to ensure normal
ocular resurfacing
-
Recurrent ulceration and irregular corneal surface, corneal NV
-
Secondary causes: chemical burn, thermal burn, CL wear, cicatricial
pemphegoid, trachoma, SJS, pterygium, ocular surgery, dysplastic and
neoplastic lesions of the limbus
-
Impression cytology
-
Limbal transplantation
Invasion of an Intact Corneal Epithelium: Corynebacterium diphtheriae
Neisseria gonorrhea and meningitidis
Haemophilus
Listeria
Shigella

Biofilm in Streptococcus inhibits recognition of the bacteria by the immune system and
accounts for the paucity of inflammation and chronic nature characteristic of
crystalline keratopathy

Dermatoblepharitis: Staph and Streptococcus, HSV and VZV

Angular Blepharitis: Staph and Moraxella
Conjunctivitis: Adenovirus, HSV, Staph and Strep, Chlamydia, Neisseria, Haemophilus,
Moraxella
Keratitis: HSV, Pseudomonas, Staph and Strep, Moraxella, Fungi, Acathamoeba
Dacroadenitis: EBV, Mumps, Staph and Strep
Canaliculitis: Actinomycetes
Dacryocystitis: Staph and Strep
Molluscum contangiosum: umbilicated wartlike lesion; Henderson-Patterson
intracytoplasmic inclusion

Gram +peptidoglycan and teichoic acid

Cocci Staph: grapelike clusters, singly, pairs or in chains
Strep: in pairs and chains Strep pyogenes β hemolysis
Strep pneumoniae α hemolysis; lancet shape diplococci
Enterococcus: important cause of endophthalmitis

Rods Proprionibacterium: beaded appearance; chronic postop endophthalmitis

Corynebacterium: pleomorphic bacilli producing palisading or cuneiform
patterns
Bacillus: spore forming, aerobes; post traumatic endophthalmitis
Clostridium: anaerobe

Gram - lipopolysaccharide (endotoxin) and thin peptidoglycan

Cocci Neisseria: hyperacute conjunctivitis, keratolysis of the corneal stroma and
perforate the cornea
Bean shaped gram negative diplococci seen within neutrophils
(intracellular)
Chocolate agar and Thayer Martin media
Rods Pseudomonas: slender gram negative rods which are contaminants of water
Enterobacteriaceae: Salmonella
Shigella
Proteus
Escherichia coli
Enterobacter
Citrobacter
Klebsiella
Serratia: able to survive preserved contact lens disinfection
solutions

Haemophilus: coccobacilli to short rods; obligate parasite of mucous membrane

 Bleb infection following glaucoma filtering surgery (along with
strep)
Chocolate agar (requires hemin and NAD)
Bartonella henselae

Gram + filaments: Mycobacterium: nonmotile aerobic weakly gram + but acid fast
M fortuitum and M chelonei: ulcerative keratitis during
refractive sx
Lowenstein-Jensen culture media
Nocardia: gram + and weakly acid fast
Actinomyces: gram +, non acid-fast anaerobic; canaliculitis

Chlamydia: obligate intracellular parasites of mucosal epithelium with dimorphic life

cycle
intraCytoplasmic inclusion bodies (intranuclear inclusion in HSV and HZV)
A to C: Trachoma
D to K: genital infection and keratoconjunctivitis
SPIROCHETES
Treponema pallidum: venereal syphilis
Fine and corkscrew shaped
MHA-TP and FTA-ABS test are specific; reactive for life
RPR and VDRL are non-specific (RA, SLE); assess response
to treatment
Borrelia burgdorferi: Lyme disease

FUNGI: cell walls (stain w/ Gomori methenamine silver) are rigid and contain chitin and
polysaccharide
Dimorphic fungi: yeast in the host and molds in room temp laboratory; highly
virulent
Yeast: Candida: most commonly isolated yeast; immunocompromised
Ocular topical corticosteroids reduce local cell mediated immunity
Cryptococcus neoformans
Rhinosporidium

Septate Filamentous: Fusarium, Aspergellus, Curvularia

Follow trauma with vegetative matter
Blood agar; Sabourand and BHI at room temp
Nonseptate Filamentous: Mucor, Rhizopus, Pneumocystis carinii
Immunocompromised: DM and renal failure

PROTOZOA
Acanthamoeba: motile trophozoite and dormant cyst
Corneal scraping (chemical stain & culture) or Corneal biopsy
(histochemistry)
Non-nutrient agar with an overlay of E. coli
Calcofluor white (cysts)
Acridine Orange (cysts and trophozoites)
H&E and PAS stain, Grams and Giemsa
Microsporidia: obligate intracellular parasites
Toxoplasma gondii: most common parasitic infections of human; causes
chorioretinitis

Recommended Stains and Culture Media for Microbial Keratitis

 Organism Stain Media
Aerobic bacteria Gram Blood Agar Plate
Acridine orange Chocolate Agar
Thioglycolate broth
Anaerobic bacteria Gram Anaerobic Blood Agar
Acridine orange Phenylethyl alcohol agar
Thioglycolate broth
Neisseria & Gram Chocolate Agar
Haemophilus Thayer-Martin
Mycobacterium Gram Blood agar
&Nocardia Acid-fast (red) Lowenstein-Jensen agar
Lectin
Fungi Gram Blood agar (25°C)
Acridine orange (green) Saboraud’s agar (25°C)
Calcofluor white (green) Brain-heart infusion (25°C)
Acanthamoeba Acridine orange (orange) Nonnutrient agar with E. coli
Calcofluor white (green) overlay
Blood agar
Buffered charcoal-yeast extract
agar

Infectious Diseases

Adenoviral Keratoconjunctivitis
1. Simple follicular conjunctivitis
2. PharyngoConjunctival Fever (PCF): 3 and 7
o fever, headache, pharyngitis and preauricular adenopathy
3. Epidemic KeratoConjunctivitis (EKC): 8, 19 and 37
o preceded by URTI, with preauricular adenopathy
o severe bilateral follicular conjunctivitis, punctate epithelial keratitis,
petechial conjunctival hemorrhages, pseudomembranes or frank
membranes
o within 7-14 days, multifocal subepithelial (stromal) corneal infiltrates
-
Treatment: cool compress and artificial tears; topical antibiotic if with
mucopurulent discharge
-
Topical corticosteroids: membranes or photophobia, bilateral subepithlial
infiltrates
-
Viral shedding may persist for 10-14 days after onset of clinical sxs

Acute Hemorrhagic Conjunctivitis

-
Enterovirus type 70 and Coxsackie A24, Adenovirus type 11
-
Highly contagious; sudden onset of follicular conjunctivitis asso w/ multiple
petechial hemorrhage

Herpes Simplex Eye Disease

Primary Ocular Infection
o unilateral blepharoconjunctivitis, follicular
o dendritic epithelial keratitis
 o vesicles on the skin or eyelid margin
o palpable preauricular lymph node

Recurrent Ocular Infection

o blepharoconjunctivitis
o epithelial keratitis: arborizing dendritic epithelial ulcers w/ terminal
bulbs
ulcer margin stains with rose bengal while bed stains
w/ fluorescein
ghost image or ghost dendrite
reduction in corneal sensation
resolves spontaneously but treatment shortens course
& ↓ neuropathy
topical TFT 1% 8x/day or vidarabine 3% ointment 5x/day
discontinued within 10-14 days to avoid toxicity
topical steroids: contraindicated in active herpetic
epithelial keratitis

o stromal keratitis: most common cause of infectious corneal blindness in

US
Interstitial keratitis: stromal haze in the absence of
epithelial ulceration
Disciform keratitis: corneal stromal and epithelial edema,
KPs
Necrotizing keratitis: suppurative corneal inflammation
HEDS
 topical corticosteroid together with antiviral treatment
o ↓ persistence and progression of stromal
inflammation
o shorten the duration of HSV keratitis
o ↓ rate of recurrent HSV keratitis
o help preserve vision
 No additional benefit of oral acyclovir in treating active
HSV stromal keratitis in those pxs also receiving
concomitant topical steroid and trifluridine
 Oral acyclovir is preferred for necrotizing herpetic stromal
keratitis
o Iridocyclitis: unilateral ↑ IOP due to trabeculitis; patchy iris
transillumination
 Oral acyclovir is given for HSV iridocyclitis + topical
steroids
PKP: visually significant stromal scarring and astigmatism not correctable by
spectacles or CL
Oral antiviral may improve graft survival by reducing the risk of
recurrence
Prognosis approaches 80% in eyes w/o signs of active inflammation for
at least 6 mos

Herpes SimplexVirus Varicella Zoster Virus

Dermatomal distribution Incomplete Complete
Pain Moderate Severe
Dendrite morphology Central ulceration with Smaller without central
terminal bulbs; geographic ulceration no terminal
 in presence of bulbs; dendritiform mucous
corticosteroid plaques occur later
Skin scarring No Common
Postherpetic neuralgia No Common
Iris atrophy Patchy Sectoral
Bilateral involvement Uncommon No
Recurrent epithelial Common Rare
keratitis
Corneal hypoesthesia Sectoral or diffuse May be severe
Viral replication causes Sloughing of epithelial cells Swollen epithelial cells and
heaped-up

Herpes Zoster Ophthalmicus

-
painful vesicular dermatitis typically localized to a single dermatome on the
thorax (T3 to L3) or face (CN V ophthalmic division)
-
Hutchinson’s sign: rash on the tip of the nose indicating probable ocular
involvement (nasociliary)
-
Nummular corneal infiltrates are characteristic of zoster stromal keratitis
-
Treatment: Oral Antiviral Therapy: Famciclovir 500 mg TID given
for 7-10 days
Valacyclovir 1 gram TID started w/in
72 hrs of the
Acyclovir 800 mg 5x/day onset of skin
lesions
 Reduce viral shedding from vesicular skin lesions
 Reduce chance of systemic dissemination of the virus
 Reduce incidence and severity of most common ocular
complications
 Reduce duration of postherpetic neuralgia
Topical corticosteroids and cycloplegics are indicated for
keratouveitis
Capsaicin cream: post herpetic neuralgia

Blepharitis
-
symptoms upon awakening
-
poliosis (white lashes); madarosis (lash loss)
-
chronic: persist for 4 weeks or more
-
Moraxella: chronic angular blepharoconjunctivitis
-
Treatment: antibacterial and anti-inflammatory; eyelid hygiene; artificial tears

Staphylococcal Seborrheic MGD

Location Anterior eyelid Anterior eyelid Posterior eyelid
Loss/whitening of Frequent Rare (-)
lashes
Eyelid crusting Hard, fibrinous Oily or greasy +/-
scales; Hard,
matted crust
Eyelid ulceration Occasional (-) (-)
Conjunctivitis Papillary with Mild injection, Mild-mod injection
mucopurulent follicular or Papillary tarsal rxn
discharge papillary tarsal rxn
Keratitis Inferior PEE Inferior PEE Inferior PEE
Marginal infiltrates (punctate epithelial Marginal infiltrates
 Vascularization erosion) Vascular pannus
Phlyctenulosis (type
IV)
Aqueous tear Occasional Occasional Occasional
deficiency
Rosacea (-) + ++

Hordeolum: Staphylococcus
External: Gland of Zeis of lash follicle
Internal: Meibomian gland

Bacterial Conjunctivitis

Course of Onset Severity Common Organisms

Slow (days to weeks) Mild- Moraxella lacunata
moderate Enterobacteriaceae
Pseudomonas sp
Proteus sp.
Staphylococcus aureus
Acute or subacute Moderate- Staph aureus (blepharoconjunctivitis)
- less than 3 weeks severe Strep pneumoniae (most common)
duration Haemophilus influenzae (children esp w/
otitis media)
Hyperacute (<24hrs) Severe Neisseria gonorrheae
Neisseria meningitidis

Treatment:
Acute Conjunctivitis: Erythromycin or bacitracin ointment
Gramicidin-Neomycin-Polymyxin B eyedrops QID
for
Trimethoprim-Polymixin B eyedrops 5-7
days
Fluoroquinolone (Ciprofloxacin, Ofloxacin, Levofloxacin)
Tobramycin or Gentamicin eyedops

Gonococcal Conjunctivitis: Systemic Antibiotics

Ceftriaxone 1 gm/IM; 1 gm IV every 12 hrs x 3 days
Spectimycin 2 gm/IM
Ciprofloxacin 500mg
Ofloxacin 400mg BID for 5 days
Topical Antibiotics
Bacitracin, Erythromycin and Gentamicin ointment
Ciprofloxacin eyedrop / Fluoroquinoline
Concomittant Chlamydia
Minocycline / Doxycline 100mg BID
Erythromycin 250mg QID for 1
week
Tetracycline 500mg QID
Azithromycin 1 gm once

Neonatal Gonococcal conjunctivitis: Ceftriaxone 25-50mg/kg up to 125 mg IV/IM

single dose
Cefotaxime 100mg/kg IV/IM single dose
 Erythromycin/Gentamicin ointment /
Fluoroquinolone drops

Neonatal Chlamydial conjunctivitis: Erythromycin 12.5mg/kg oral or IV QID for 14

days

Chlamydial Conjuctivitis
-
Chlamydia trachomatis: obligate intracellular bacterium
-
Trachoma: serotypes A-C
o Severe follicular reaction most prominent in the superior tarsal
conjunctiva
o Arlt’s Line: linear or stellate scarring of the superior tarsus
o Herbert’s pit: involution and necrosis of follicles resulting to limbal
depression
o Vascular pannus most marked on the superior limbus
-
Adult and Neonatal Inclusion Conjunctivitis: serotypes: D-K
-
Lymphogranuloma venereum: L1, L2 and L3

Parinaud Oculoglandular Syndrome

-
granulomatous conjunctivitis with regional lymphadenopathy
-
Cat-scratch disease is the most common cause; primary causative agent is
Bartonella henselae
-
Treatment: Azithromycin, Erythromycin and Doxycycline

Bacterial Keratitis
-
Predisposing Factors: contact lens wear, trauma, contaminated ocular meds,
impaired defense mechanism, altered structure of the corneal surface
-
Pseudomonas: stromal necrosis with a shaggy surface, adherent mucopurulent
exudates, hypopyon
Most common organism in soft contact lens wearers
-
Infectious crystalline keratopathy: α hemolytic Strep
Densely packed, white, branching aggregates of
organisms
Steroid use, CL wear, infected corneal grafts

Organism Examples Antibiotic Topical Dose

Gram + cocci Staphylococcus Cefazolin 50mg/ml
Streptococcus Vancomycin 50mg/ml
Gram - cocci Neisseria Ceftriaxone 50mg/ml
Ceftazidime 50mg/ml
Gram - rods Pseudomonas Tobramycin 9-14mg/ml
Enterobacteria Ceftazidime 50mg/ml
ceae Fluoroquinolone 3mg/ml
Mycobacterium Amikacin 20mg/ml
No organism / Cefazoline 50mg/ml
multiple Tobramycin 9-14mg/ml
Fluoroquinolone 3mg/ml

Gram positive bacteria: Cefazolin and Cefuroxime Gram negative bacteria:

Tobramycin
Vancomycin Amikacin
 Neosporin
Gentamicin
Bacitracin
Ceftazidime

Fluoroquinolone
Clinical Response to Antibiotic Therapy:
1. Reepithelialization
2. Blunting of the perimeter of the stromal infiltrates
3. Decreased density of the stromal infiltrates
4. Reduction of stromal edema and endothelial inflammatory plaques
5. Reduction of AC inflammation
6. Cessation of corneal thinning
Corticosteroids
-
to decrease tissue destruction caused by neutrophils
-
should not be used in the initial phase of treatment
-
favorable clinical response to antibiotic therapy before initiating topical
corticosteroids
-
frequent follow-up examination and compliance with appropriate antibiotic
therapy
-
no associated virulent or difficult to eradicate organism
-
Prednisolone acetate 1% every 4-6 hours; monitored 24 and 48 hours after
initiation of therapy
PKP
-
disease progresses despite therapy
-
descematocoele formation or perforation
-
keratitis unresponsive to antimicrobial therapy
-
peripheral iridectomies are indicated (seclusio pupillae from inflammatory
papillary membranes)
-
postoperative antibiotics, cycloplegics and intense topical corticosteroids

Fungal Keratitis
-
trauma with plant or vegetable material, trauma related to contact lens wear,
topical corticosteroid use, corneal surgery (PKP, RK) and chronic keratitis (HSV,
HZV, vernal/allergic conjunctivitis)
-
infiltrate with irregular feathery and filamentous margins; multifocal or satellite
infiltrates; deep stromal infiltrates,endothelial plaques; hypopyon; intense
suppuration
-
Treatment: Natamycin / Oral Ketoconazole: Filamentous (Fusarium-most
common);
Amphotericin B / Oral Fluconazole: Yeast (Candida)
Aspergillus (filamentous): Amphotericin B; Oral Itraconazole (also for
candida)
Acanthamoeba Keratitis
-
free-living ubiquitous protozoa found in fresh water and soil, resistant to killing
by freezing, desiccation and chlorine
-
associated with contact lens wear using home made saline solution
-
diffuse punctate epithliopathy or dendritic epithelial lesions; central stromal
infection; partial or complete ring infiltrate in the paracentral cornea; enlarged
corneal nerves (radial perineuritis)
-
Non-nutrient agar with E coli overlay, or BAP; stains with Giemsa, PAS,
Calcofluor or Acridine
-
Characteristic trails form as the motile trophozoite travel across the culture
plate
 -
Difference with HSV keratitis
o Non-contiguous or multifocal pattern of granular epitheliopathy (HSV
contiguous)
o Disproportionate severe pain (HSV: hypoesthesia and disproportional
mild pain)
o Risk factor of contact lens use and exposure to contaminated freshwater
o Failure to respond to initial antiviral therapy
-
Treatment: Epithelial debridement + anti-amebic therapy for 3-4 months
-
Stromal Infiltrates: treat for 6-12 months
o Diamidines: propamidine, hexamidine
o Imidazole/Triazole: miconazole, itraconazole, clotrimazole, ketoconazole
o Biguanides: polyhexamethylene biguanide, chlorhexidine
o Aminoglycoside: neomycin, paromomycin

Immune Mediated Diseases

Contact Dermatoblepharitis
-
Acute onset as anaplylactic reaction : Type I IgE mediated hypersensitivity
o Topical anesthetics & antibiotics: bacitracin, cephalosporin, penicillin,
sulfa, tetracycline
-
delayed onset: 24-72 hours following exposure: Type IV cell mediated or delayed
hypersensitivity
o cycloplegics (atropine) aminoglycoside, antiviral and preservatives
(thimerosal, EDTA)

Vernal Keratoconjunctivitis
-
seasonally recurring, bilateral inflammation predominantly in male children, (+)
FHx of atopy
-
both type I and IV hypersensitivity reaction
-
diffuse papillary hypertrophy more prominent in the upper eyelid; giant papillae
resembling cobblestones on the upper tarsus
-
Horner-Trantas dots: macroaggregates of degenerated eosinophils & epithelial
cells at the limbus
-
Pannus most commonly in the superior cornea but 360° corneal vascularization
may develop
-
Shield ulcer: non-infectious epithelial ulcer with underlying stromal
opacification
-
Treatment: topical antihistamines, mast-cell stabilizer (cromolyn sodium and
lodoxomide), topical NSAIDS (ketorolac), topical corticosteroid, topical
cyclosporine

Atopic Keratoconjunctivitis
-
history of atopic dermatitis, type 1 immediate hypersensitivity, year round
disease in older pxs
-
papillae are small and medium sized in the upper and lower palpebral
conjunctiva
-
extensive corneal vascularization and opacification secondary to chronic
epithelial disease
-
eosinophils less numerous and less granulated
-
conjunctival scarring and symblepharon formation
-
characteristic PSC & multifaceted or shield-shaped anterior subcapsular lens
opacity
-
Treatment: same
Contact Lens-Induced Conjunctivitis
-
mild papillary reaction (papillae <0.3mm in diameter) on the superior tarsal
conjunctiva; punctuate epithelial erosions and peripheral corneal infiltrates and
vascularization
-
Giant Papillary Conjunctivitis (>0.3mm): soft contact lens wearers; excessive
mucous discharge
-
Treatment: Discard offending contact lens and improve CL hygiene; use
preservative free agents

Stevens-Johnson Syndrome
-
immune complex deposition in the dermis and conjunctival stroma
-
drugs: Penicillin, Ampicillin, Sulfonamides, Salicylates, Isoniazid and
Anticonvulsants
-
organisms: Strep, HSV, Adenovirus and Mycoplasma
-
Erythema multiforme minor: skin only
-
Erythema multiforme major: skin and mucous membrane
-
Acute inflammatory vesiculobullous reaction, more common in children and
young female adults
-
Classic “target” lesion: red center surrounded by a pale ring and then a red ring
-
Bullous lesions with membrane or pseudomembrane formation and
cicatrization, symblepharon
-
Treatment: Ocular lubrication with artificial tears and ointments is the mainstay
Systemic corticosteroids: oral prednisone 1mkd
PKP has an extremely poor prognosis

Ocular Cicatricial Pemphigoid

-
cytotoxic type II hypersensitivity; autoantibodies against cell surface antigen in
the BM
-
chronic vesiculobullous disease affecting the conjunctiva and other mucous
membranes
-
female older than 60; bilateral
-
Stage I: subepithelial fibrosis
-
Stage II: loss of goblet cells; shortening of the fornices
-
Stage III: symblepharon formation
-
Stage IV: EOM restriction due to extensive fibrosis and adhesions between the
lid and the globe
-
Inferior forniceal depth <8mm and subtle inferior symblepharon detected when
lower lid is pulled down while the patient look up
-
Conjunctival Biopsy sent for immunofluorescent and immunoperoxidase staining
o C3, IgG, IgM and / or IgA localized in the BMZ of the conjunctiva
-
Treatment: Dapsone (caution in G6PD deficiency and sulfa allergy)
Cyclophosphamide (Cytoxan) 1.5-2.0 mkd (target is ↓WBC to 2000-
3000 cells/μL)
Azathioprine (Imuran) and Methotrexate
Topical corticosteroid to suppress immediate inflammatory response
and exacerbation

Thygeson Superficial Punctate Keratitis

-
bilateral asymmetrical with waxing and waning appearance
-
hallmark finding is multiple slightly elevated corneal epithelial lesions during
exacerbations
 -
greatest density typically appears in the central cornea; stains w/ fluorescein
and rose bengal
-
patient’s symptoms may far exceed the apparent signs
-
Treatment: artificial tears and BCL; topical corticosteoids (FML)

Interstitial Keratitis with Infectious Disease

-
type IV hypersensitivity
-
cellular infiltration & vascularization w/o involvement of epithelium and
endothelium
-
HSV, VZV, Mycobacterium, Measles virus, EBV, Chlamydia

Peripheral Ulcerative Keratitis

-
occurs most often in association with rheumatoid arthritis
-
conjunctival biopsy: immune-mediated vaso-occlusive disease
-
peripheral corneal infiltration or frnak stromal melting may be the 1 st sign;
keratolysis
-
usually unilateral and limited to one sector, within 2 mm of the limbus
-
Treatment: lubrication, patching/BCL, topical corticosteroid;
immunosuppressants

Mooren’s Ulcer
-
PUK of unknown cause; unilateral (slowly progressive) or bilateral (rapidly
progressive)
-
Chronic, progressive, painful idiopathic ulceration of the peripheral corneal
stroma and epithelium
-
Starts peripherally and spreads circumferentially and then centripetally with a
leading undermined edge of de-epithelized tissue; slower movement of
ulceration proceeds toward the sclera
-
Treatment: topical corticosteroids or cyclosporine, contact lens, acetylcysteine,
immunosuppresive

Episcleritis: bright red or salmon pink color will blanch with application of topical
phenylephrine
Scleritis: - asso with systemic immunologic disease (RA, SLE, AS, Wegener,
polyarteritis nodosa, GCA) and infectious diseases (TB, HZV, SY, Hansen
disease); 4th to 6th decades; women
-
significant pain worsen at night, tender to touch; violaceous hue; inflamed
vessels have a crisscross pattern which cannot be moved with a cotton-
tipped applicator
-
scleromalacia perforans: necrotizing scleritis without inflammation
-
sclerokeratitis: with fibrosis and lipid deposition; herpes zoster scleritis and
rheumatic dse
-
complications: peripheral keratitis, uveitis, cataract, glaucoma and scleral
thinning
-
Treatment: Topical corticosteroid, oral NSAIDs or corticosteroids (No to Depot
steroid)
High dose IV steroids or immunosuppressive therapy

Neoplastic Disorders

Conjunctival Papilloma
-
HPV 6 & 11: verruca vulgaris (wart) of the eyelid skin; pedunculated papilloma
of the conjunctiva
-
HPV 16 & 18: dysplastic or carcinomatous lesion, cervical carcinoma
 -
Pedunculated papilloma with small corkscrew blood vessels
-
Sessile papilloma at the limbus has a flat base; resemble a strawberry
-
Signs of dysplasia: keratinization (leukoplakia), inflammation and invasion
-
Regress spontaneously; cryotherapy, excision with cryo or MMC; recurrences
are frequent
Conjunctival Intraepithelial Neoplasia
-
does not invade the underlying basement membrane; exposed areas of the
bulbar conjunctiva
-
light complexion, older male, smokers, exposed to petroleum products and sun
over long periods
-
acanthosis, dysplasia, hyperkeratosis, parakeratosis, dyskeratosis
-
Treatment: Excisional biopsy with cryotherapy
Squamous Cell Carcinoma
-
Most common malignant epithelial tumor of the conjunctiva
-
broad base along the limbus grow outward with sharp borders and appear
leukoplakic
-
ultraviolet radiation is an important influence, large conjunctival feeder blood
vessels
-
invasion beneath the epithelial basement membrane; locally invasive and can
metastasize
-
Treatment: excision 4 mm beyond the clinically apparent margins of the tumors
with then lamellar scleral flap beneath the tumor; remaining sclera with
absolute alcohol; cryotherapy
-
extensive spread necessitates exenteration; radiation

Sebaceous Adenocarcinoma
-
more common on the upper eyelid because of more meibomian glands
-
painless, slow-growing, firm, nonmobile, yellowish nodule; intraepithelial
pagetoid spread into the conjunctiva with inflammation; enlarged preauricular
lymph node may indicate metastatic spread
-
Treatment: wide excision with tumor free margins / exenteration with
radiotherapy

Malignant Melanoma
-
conjunctival melanoma can metastasize but has a better prognosis than
cutaneous melanoma
-
may arise from acquired nevi, primary acquired melanosis; intralymphatic
spread increases the risk of metastasis to regional lymph nodes, the brain and
other sites
-
most commonly in the bulbar conjunctiva or at the limbus
-
heavy vascularization; grow in a nodular fashion; can invade the globe or orbit
-
Treatment: Excision of conjunctiva 4mm beyond the clinically apparent margins
of the tumor along with a thin lamellar scleral flap beneath the tumor, absolute
alcohol and cryotherapy

Epibulbar Dermoid Tumor

-
inferotemporal globe or temporal limbus
-
associated with Goldenhar syndrome (oculoauriculovertebral dysplasia):
autosomal dominant
o Triad: epibulbar dermoid in the inferotemporal limbus
facial anomalies: eyelid coloboma, preauricular skin tags, aural
fistula
skeletal anomalies
Dermolipoma: dermoid containing adipose tissue; occurs superotemptorally and may
extent posteriorly
Congenital Anomalies

Cryptophthalmos
-
bilateral “hidden eye” autosomal recessive
-
ablepharon: eyelids and associated structures of the brows and lashes fail to
form
-
pseudocryptophthalmos: eyelids & asso structures form but fail to separate
(ankyloblepharon)
-
dermoid transformation of the cornea and conjunctiva into skin
-
absence of the eyelid structures, lacrimal glands and canaliculi
-
absence or transformation into CT of the iris, Schlemm’s canal, TM,AC and lens

Microphthalmos
-
small disorganized globe; malformed eye
-
failure of the fetal fissure to close properly and colobomatous defects are often
present

Nanophthalmos
-
small, functional eye with relatively normal internal organization and
proportions
-
high degree of hyperopia (7-15D) due to a short axial length (15-20mm); high lens
to eye volume ratio which can lead to angle closure glaucoma, narrow palpebral
fissure, thickened sclera

Blue Sclera
-
generalized scleral thinning with increased visibility of the underlying uvea
-
associated with Osteogenesis imperfecta, Ehlers-Danlos syndrome
-
kyphoscoliosis, joint extensibility and elastic skin

Microcornea
-
clear cornea with normal thickness but diameter is <10mm (or 9mm in newborn)
-
fetal arrest of growth in the fifth month

Megalocornea
-
X-linked bilateral, non progressive corneal enlargement measuring >13.0-
16.5mm in diameter
-
Normal thickness, endothelial cell count and clarity but may be steeper
keratometrically
-
Normal axial length in contrast to buphthalmos of congenital glaucoma

Cornea Plana
-
flat cornea whose radius of curvature is <43D and reading of 20-30 D are
common
-
corneal curvature that is the same as the adjacent sclera is pathognomonic
-
associated with sclerocornea and microcornea, hyperopia

Keratectasia and Congenital Anterior Staphyloma

-
protrusion of the opaque cornea between the eyelids at birth
-
Descemet’s membrane and endothelium are absent
-
Staphyloma: presence of a uveal lining of the cornea

Circumscribed Posterior Keratoconus

 -
localized central/paracentral indentation of the post. cornea with no protrusion
of the ant. surface
-
loss of stromal substance which can lead to corneal thinning (1/3 of normal)
-
Descemet’s membrane and endothelium are usually present
-
Unilateral, non-progressive and sporadic

Sclerocornea
-
non-progressive, non-inflammatory scleralization of the cornea making the
limbus ill-defined
-
no sex predilection, and 90% are bilateral; mostly are sporadic

Congenital Hereditary Stromal Dystrophy

-
bilateral central superficial corneal clouding present at birth; peripheral cornea
is clear
-
no photophobia, edema or tearing but opacities can be dense to reduce vision
Congenital Hereditary Endothelial Dystrophy
-
bilateral congenital corneal edema (DDx: birth trauma and congenital GL)
ground-glass
-
abnormal differentiation of neural crest ectoderm that forms corneal
endothelium
-
CHED 1: autosomal dominant; presents in the 1st and 2nd year of life; slowly
progressive
-
CHED 2: autosoma recessive; present at birth, with nystagmus; remains
stationary

Chemical Injuries
-
Alkali: saponification of fatty acids in cell membranes and ultimately cellular
disruption
-
Acid: denature and precipitates proteins in tissues

Traumatic Hyphema
-
vessels of the peripheral iris or anterior ciliary body
-
rebleeding from 3-30% frequently between 2-5 days after injury
-
Avoid CAI and osmotic agents in patients with sickle cell because of their
tendency to reduce pH and lead to hemoconcentration, exacerbating sickling of
RBCs
Surgical Intervention:
o To prevent Optic Atrophy
 IOP averages >50 mmHg for 5 days
 IOP averages >35 mmHg for 7 days
o To prevent Corneal Bloodstaining
 IOP averages >25mmHg for 6 days
 Indication of early bloodstaining
o To prevent PAS
 Before total hyphema persists for 5 days
 Before diffuse hyphema persists for 9 days
o Patients with sickle hemoglobinopathies
 IOP averages ≥25mmHg for 24 hours
 Repeated transient elevations >30mmHg

Indications for Pterygium Excision Treatment:

1. persistent discomfort - bare sclera: 40-50% recurrence
2. vision distortion - excision with MMC
3. >3-4mm - conjunctival autograft: 2-5% recurrence
 4. progressive growth toward the visual axis
5. restricted ocular motility

☺ Elisa P. Fermin, M.D.