-
POSTULATED RISK FACTORS FOR AMD
AgeingThe Framingham Eye study (1976) showed the prevalence65-74
years- 11%75-85 years- 28%
GenderBlue Mountains study (2002) suggests that 5-year incidence
of neovascular AMD among women is double that of men.
Smoking The Beaver Dam Study (1992) disclosed a relationship
between the development of exudative lesions and a history of
current cigarette smoking.
-
Cardiovascular Risk factorsHypertension: Rotterdam study (2003)
suggests positive correlation between high blood pressure and
increased incidence of AMD.
LightInitially postulated hypothesis: UV-damage by
photo-oxidative damage via reactive oxygen intermediates.The Blue
Mountains Eye Study (2002) disclosed no relationship between light
and AMD.
POSTULATED RISK FACTORS FOR AMD
-
NutritionSeveral studies (including AREDS) have described the
beneficial effects of dietary carotenoids, anti-oxidants, Zn and
omega-3 fatty acid in slowing the course of the disease.
Exogenous Post Menopausal OestrogenThe use of exogenous
supplements in post menopausal women lowered risk of AMD in a study
performed by the Eye Case Control Study Group.
POSTULATED RISK FACTORS FOR AMD
Chart1
50
29
21
Risk factors for AMD
Sheet1
Risk factors for AMD
Genetics50
Smoking29
Other factors21
4th Qtr
To resize chart data range, drag lower right corner of
range.
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GENETICSFamily history of macular degeneration:Autosomal
dominant with variable penetrationIn first degree relative with
macular degeneration, chances is about 2.5 times.
Macular Degeneration Gene:Few studies* have described the
increased risk of AMD associated with polymorphisms of complement
factor H (HF1/CFH)single nucleotide polymorphisms on 1q32, 6p21,
and 10q26 are the risk for development of AMDThe odds of developing
macular degeneration are increased by about 2.5 to 5.5 times if one
has the CFH gene variant.
*Moshfeghi DM, Blumenkranz MS, Retina. 2007 Mar;27(3):269-75
-
AMD: SYMPTOMSInitial symptoms: Straight lines appear wavy Blurry
vision Distorted vision Objects may appear as the wrong shape or
size A dark empty area in the centre of vision
-
AMD: SYMPTOMSPatients ability to perform normal daily tasks such
as reading, sewing, telling the time, driving are greatly
impaired.
-
FoveolaFoveaMACULAPara-foveal zonePeri-foveal zoneMACULA:
ANATOMYUmbo
-
RETINAL PIGMENT EPITHELIUMThe retinal pigment epithelium (RPE)
is a single layer of hexagonally shaped cells & attached to the
photoreceptor layer.
Functions - Maintain the photoreceptorsAbsorption of stray light
Formation of the outer blood retinal barrierPhagocytosis and
regeneration of visual pigment
-
Bruchs membrane separates the RPE from vascular choroid.
Function of Bruchs membrane is to provide support to the
retina.
Choroid capillaries are a layer of fine blood vessels that
nourishes the retina and provides O2.
-
TYPES
-
DRY AMDAccounts for about 90% of all casesAlso called atrophic,
non-exudative or drusenoid macular degeneration
Clinically , dry AMD may manifest- Stage of drusen and/or
hyperpigmentation Stage of incipient atrophy (non geographic
atrophy) Stage of geographic atrophy
-
DRY AMDDrusen
-
Insufficient oxygen and nutrients damages photoreceptor
molecules
With ageing, the ability of RPE cells to digest these molecules
decreases
Excessive accumulation of residual metabolic debris and hyaline
material (drusen)
RPE membrane and cells degenerate and atrophy sets in and
central vision is lostDRY AMD
-
Drusen:
Drusen are aggregation of hyaline material located between
Bruchs membrane and RPE.
Drusen are composed of metabolic waste products from
photoreceptors.
Hypo/hyper pigmentation of RPE may be present.DRY AMD
-
Types:Small: 125
Hard:generally small (63 ), pale yellow, ill defined, fluffy
marginsHigh risk for neovascular AMD
-
Soft Drusen:Membranous:63-175 Pale, shallow appearing
drusensGranular:About 250 Solid appearing drusensSerous:>500
Have pooled serous fluidblister like appearanceMay result in serous
PED
-
HISTOPATHOLOGYDrusen appear as focal areas of the eosinophilic
material between the basement membrane of RPE & BM.
Deposits on the internal side of RPE basement membrane called
basal laminar deposits & on its external aspects called basal
linear deposits.
Basal linear deposits are believed to form soft drusen with the
passage of time & are more common in eyes effected by
neo-vascular AMD.
Drusen
-
Diagnostic criteria*Degenerative disorder in persons >50
years, characterized by the presence of any of the following:Soft
drusen (>63 )RPE abnormalities- areas of hypo/hyperpigmentation
(excluding pigment surrounding small, hard drusen)Visual acuity
(VA) is not a criterion for the diagnosis
*International Epidemiological Age-related Maculopathy study
Group
-
DRY AMD
-
DRUSEN
-
GEOGRAPHIC ATROPHY
-
DRY AMD: COURSE AND VISUAL PROGNOSISPatients with only drusen
not have much loss of vision, but require additional magnification
of the text and more intense lighting to read small points.
Presence of large drusen (>63 microns in diameter) is
associated with a risk of the late form of the disease like
CNV.
Geographic atrophy- severest form of the dry AMD, RPE atrophy
>175 microns with exposure of the underlying choroidal
vessels.
-
EXUDATIVE MACULAR DEGENERATION( WET OR NEOVASCULAR AMD )
Accounts for about 10%
The pathology of neovascular AMD is choroidal neovascularisation
with the formation of a subretinal/choroidal neovascular membrane
(SRNVM/CNVM) The CNVM lead to haemorrhage and fibrovascular
proferation and subsequent scarring.
Age related Bruchs membrane change may be especially important
in exudative macular degeneration, this change includes thickening
of Bruchs membrane, drusen and other metabolic accuminata such as
lipids and loss of basal connections with the RPE.
Pigment epithelial detachment may occur in relation to Bruchs
membrane change.
-
Photoreceptors and pigment epithelium send a distress signal to
choriocapillaries to make new vessels
New vessels grow behind the macula
Breakdown in the Bruchs membrane
Blood vessels are fragile
Leak blood and fluid
Scarring of macula
WET AMDPotential for rapid and severe visual damage
-
WET AMD
-
Diagnostic criteria*persons >50 years, characterized by the
presence of any of the following:choroidal neovascularizationserous
retinal pigment epithelial detachmenthemorrhagic retinal pigment
epithelial detachmentfibrotic scar in the maculaWET AMD*Takahashi K
et al.Nihon Ganka Gakkai Zasshi. 2008 Dec;112(12):1076-84.
-
WET AMD
-
WET AMD
- WET AMDCNV lesion is well demarcated & its location may be
determined by closest point to the FAZ.Lesion location is
classified angiograpically as follows:-Subfoveal: under the centre
of FAZJuxtafoveal: 1-199 m from the centre of FAZExtrafoveal:
>200 m &
-
CLASSIC CNV
-
OCCULT CNV (TYPE-I)
-
OCCULT CNV (TYPE-II)
-
RPE DETACHMENT (PED) PED (Pigment epithelium detachment)
Depending on cause, it is of many types:DrusenoidSerousFibro
vascularHemorrhagic
-
RPE DETACHMENT (PED)
-
RPE TEARSpontaneously or on photocoagulation of CNV.
Visual acuity abruptly fall
Angiogram shows CNV in early & in late phase shows
hypofluorescence corresponding to heaped-up RPE with
hyperfluorescence over the torn area.
-
DISCIFORM SCAR
-
WET AMD: COURSE AND VISUAL PROGNOSISLeakage of blood or serum in
CNV may occur precipitously and associated with the abrupt loss of
vision.
Patients with CNV shows rapid decline in vision (20/200) within
weeks.
Once CNV has developed in one eye, the other eye is at
relatively high risk for the same change.
More frequently, visual acuity deteriorates more slowly and
stabilizes within 3 years.
-
AREDS Categories:No AMD (AREDS category 1)No or a few small
(
-
Visual acuityAmsler grid test: Assesses distorted or reduced
vision and small irregularities in the central field of
vision.Ophthalmoscopy: to detect drusen, as well as
neovascularizationFluorescein and ICG angiography: Determines the
presence and location of neovascularization. Aided by optical
coherence tomography.
AMD: DIAGNOSTIC TOOLS
-
Role of Antioxidants:AREDS-1 study- use of high dose of
multivitamins & antioxidants decreases the risk of progression
of ARM in those with high risk characteristics.Combination of
antioxidants and zinc (AREDS-1 Formula)-Vitamin C: 500 milligrams
(mg)Vitamin E: 400 international units (IU)Beta carotene: 15 mg
(equivalent to Vit.A 25000 IU)Zinc: 80 mgCopper (cupric oxide): 2
mg
AMD: MANAGEMENT
-
AREDS-2 Study:Lutein & zeaxanthin antioxidants
micronutrients found in human macula.Diet rich in these give some
protection against the disease.omega-3 fatty acids,docosahexaenoic
acid (DHA) and eicosapentaenoic acid (EPA) have also been shown to
help with AMD.AREDS-2 Formula-Vitamin C - 500 mgVitamin E - 400
IUBeta-Carotene - 15 mgZinc - 80 mgCopper - 2 mgLutein - 10
mgZeaxanthin - 2 mgDHA - 350 mgEPA - 650 mg
AMD: MANAGEMENT
-
Current treatment
Antiangiogenic drugs
Photodynamic therapy
Laser photocoagulation
AMD: MANAGEMENT
-
ANTI ANGIOGENICSAnti-VEGFs:reduce the growth of new blood
vessels, decrease the leakage through them.
Bevacizumab (Avastin)Ranibizumab (Lucentis)Pegaptanib sodium
(Macugen)Aflibercept (VEGF Trap-Eye)
-
Bevacizumab (Avastin)-
Full-length monoclonal antibody (150 kD)Binds all isoforms of
VEGFHas FDA approval for i.v. use in metastatic colorectal,
metastatic breast and non-small cell carcinoma of lungIs being used
off-label for choroidal neovascularization based on results of
short-term studiesDose- 1-1.25 mg, repeated 6-8 weekly.
-
Ranibizumab (Lucentis ) Recombinant humanized immunoglobulin G1,
kappa isotype, antibody fragment (Fab) (48 kD)Binds to all isoforms
of VEGF.Dose- First 3 injections of 0.5 mg (0.05 mL) four weekly
& further on physician's assessment.Comparison of AMD Treatment
Trials (CATT)Multicentre clinical trialCompare safety and efficacy
of ranibizumab and bevacizumabCurrently under way
-
Pegaptanib sodium (Macugen)
28 base ribonucleotide aptamerBinds to Heparin-binding domain of
VEGF-AInactivates VEGF-A 165,189 and 206 isoformsGiven 0.3 mg dose
six weekly minimum for two years.VISION (VEGF Inhibition Study in
Ocular Neovascularization) (2002) has shown that pegaptanib (6
weekly injections) is superior to sham injections and as effective
as PDT in teatment of CNV.
-
Aflibercept (VEGF Trap-Eye)
a fusion protein of key binding domains of human VEGFR-1 and 2
combined with a human IgG Fc fragment blocks all isoforms of
VEGF-AAlso blocks placental growth factors-1 and 2Two Phase III
clinical trials (VIEW-1 and VIEW-2) comparing aflibercept to
ranibizumab are currently ongoing.
-
COMPLICATIONS
Common-Raised intra-ocular pressureOccasionalCataract
FormationIntra-ocular hemorrhageRareEndophthalmitisRetinal
Detachment
-
Submacular excision of CNVMacular translocationRetinal
rotationHomologous Iris/Retinal pigment epithelium
transplantationAutologous RPE transplantationSURGICAL OPTIONS
-
EMERGING TREATMENTS FOR AMDRetaane (Anecortave acetate)modified
steroid promising in reducing the risk of vision loss due to the
growth of unhealthy blood vessels in wet AMD.
AdPEDF : Adenovirus-based Pigment Epithelium Derived Factora
gene that leads to the production of the protein PEDF, which helps
keep photoreceptors healthy, thereby preserving vision.
siRNA (Bevasiranib)silences the genes that lead to the growth of
unhealthy, vision-robbing blood vessels under the retina. safety
and efficacy established in a Phase II studyPhase III clinical
trial is planned
-
ATG3 (mecamylamine)a topical formulation that inhibits the
nicotinic acetylcholine receptors Currently undergoing phase II
human study
EVIZON (squalamine lactate)aminosterol with antiangiogenic
activity Derived from the liver of the dogfish shark, administered
intravenously (no eye injection)in a Phase III human study for the
treatment of wet AMD
OT-551 (antioxidant eye drops)supplement the eyes natural
defense system against disease and injury.Protection against both
cataract and dry AMDcurrently in a clinical study for geographic
atrophy (advanced dry AMD)EMERGING TREATMENTS FOR AMD (Contd.)
-
Encapsulated Cell Technology (ECT)
Developed by Neurotech, tiny capsule (6 mm) implanted into the
eye, contains retinal cells that produce a vision-preserving
protein ,Ciliary Neurotrophic Factor (CNTF) keep photoreceptors
alive and healthy, preserving vision.currently in a Phase II human
clinical trial for people with dry AMD.
EMERGING TREATMENTS FOR AMD (Contd.)
-
REHABILATATIONLow vision aids-
Individual who experiences untreatable visual loss & effects
the daily life.
Reading lamps & simple magnifiers may be beneficial.
Closed circuit television & scanning devises are also
available to provide electronic magnification & contrast
enhancement.
-
CLASSIFICATIONEndophthalmitis can be classified according to
the
Infectivity Infective / non infective ( sterile)Mode of entry
exogenous / endogenousType of etiological agent
-
Classification Infectious Sterile (Infectivity)
Exogenous Endogenous ( Mode of entry)
Post trauma Post-operative Blebitis(PEI-IOFB)
Fulminant Acute Chronic
-
Cont.Etiological agent*
BacterialFungalviralParasitic
Endophthalmitis
-
Gram positive bacteria 75%-85%Gram negative bacteria
10%-15%Fungi3%Staphylococcus epidemidis (43%)Pseudomonas
(8%)AspergillusStreptococcus spp (20%) Proteus
(5%)FusariumStaphylococcus aureus (15%)Haemophilus influenzae (1%)
Cephalosporium spp.Propionibacterium acnesKlebsiella( 0-1%)Bacillus
cereus (1%)Coliform spp (0-1%)
-
Exogenous EndophthalmitisVitreous and aqueous primary site of
involvement
Retina and uvea secondary involvement
Basically 3 types 1) post operative 2) post traumatic 3)
Blebitis
Source of infection is from exteriorMaily bacterial
-
1)Post-op Endophthalmitis
Incidence: 0.05%MC among all types: 49-76%
SurgeryBascom Palmer Eye Institute (1984-1994)Katten et
al(1984-1989)ECCE with and without PCIOL0.08%0.072%Secondary PCIOL
0.37%0.3%PPV0.05%0.05%PK0.18%0.11%Glaucoma filtration
surgery0.12%0.06%
-
Source of infectionAirborne respiratory origin, air condition in
O.T Solution and medications irrigating solutions, drops and
ointment skin antiseptic, viscoelastic and silicon oilTissue
periocular skin ,lid margin and lashes conjuctival sac, Lacrimal
sac nasal mucosa, corneal graftObjects and materials surgical
instruments, gloves, masks, IOL
Clinical Importance- all causes are preventable
-
Risk FactorsPreoperative risk factors blepharitis , active
conjunctivitis Lacrimal drainage system infection or obstruction ,
contaminated eye drops.
Operative risk factors wound abnormalities, PC rent ,vitreous
loss ,prolonged surgery & contaminated irrigation solutions
-
Types Of Presentations
Fulminant Acute Chronic (4 weeks) -gram ve -staph.epidermidis
-staph.aureus -coag.-ve cocci -streptococci delayed delayed entry
onset bleb P.acne related fungi S.epidermids
-
2)Post traumaticIncidence-2-7%(unsterile conditions &
contaminated objects)Contributes to 17-40% of all casesPenetrating
ocular trauma is main culpritCausative organisms fulminant: acute:
chronic: B. cereus S.epidermidis(MC) fungi: Streptococcus Gram.-ve
fusarium
Bacillus cerus isolated in 50% of culture positive cases causes
fulminante Endophthalmitis
-
Difficult to diagnose early.
Rapid worsening of symptoms and inflammation should be suspected
as Endophthalmitis until proved otherwise.
Ring corneal infiltrate & ring abscess is typical of
Bacillus. also assoc.with proptosis,chemosis & severe orbital
pain in 24hrs
Commoner in rural setting due to retained IOFB.
Removal of IOFB with in 24 hr.reduces risk.
-
3)Bleb related endophthalmitis4-18% of all casesAfter glaucoma
filtration surgeryMay occur at any time (months- years )after
surgeryMost of the time through intact bleb via conjuctival
floraPoor prognosis as org. are more virulentCausative organism
streptococci(MC)-faecalis,viridans,pneumoniae H.influenzae staph.
are rareClinical signs infected white bleb Vitritis Hypopyon
-
Risk factors: use of antimitotic agents,inferior
blebs,conjunctivitis,contact lens,periocular infectionsShould be
differentiated from BLEBITISBlebitis - low virulence organism -
mild intraocular inflammation - no Vitritis
-
Endogenous(Metastatic) Endophthalmitis2-15% of all
casesHematogenous spread of organism from distant source Retina and
choroid primarily involved due to high vascularity.Fungi>
bacteria Candida(MC)>AspergillusPredisposing factors - Diabetes
- immunosuppresion(AIDS,malignancies medications) - recent major
abdominal surgery - prolong indwelling catheter ( intravenous ,
TPN) - intravenous drug abuser - distant infection ( endocarditis,
meningitis, septicemia etc)no structural defect in globe
-
Clinical ApproachSymptoms: Decreased or blurred vision ( sudden
/ severe acute) ( slowly / mildchronic)Pain Photophobia Redness of
eyes Swollen eyelids Discharge White lesion in black part of the
eyeFloatersFever
-
SignsInitial visual acuity ( prognostic significance)Ocular
motility ( sign of orbital inflammation)Eyelid swollen ,
blepharospasm Conjunctiva hyperemia, chemosis, bleb examination if
presentCornea edematous, opacification , DM folds keratic
precipitate, infiltrates, occult penetrationAnterior chamber cells,
flare , fibrinous exudates and HypopyonIris muddy,boggy,resistant
to dilatation,post.synechiae
-
Pupil-absent or sluggish reaction to lightLens - Membrane ,
exudates around IOLVitreous - Vitritis , exudates , yellowish
appearance Fundus examination Absent red reflex and no fundal view
Amaurotic cats eye reflex Papilitis White lesion in retina and
chorioid Retinal hemorrhage and periphlebitisIOP- usually low,may
be high in early casesSigns of penetrating injury and Intraocular
foreign bodyWound dehiscence
- Cont.OCULAR MEDIA CLARITY (I/O) Grade 1- Media clarity, 6/12
view of the retina. Grade 2- Media clarity
-
Fungal EndophthalmitisCaused by Candida albicans, Aspergillus,
Fusarium etc.Causes - delayed post-operative endophthalmitis -
endogenous endophthalmitis in immunocompromised patients
Minimal pain, mild external ocular involvement
Progressive iridocyclitis, Vitritis ( string of pearl )
Yellow white choroidal lesion single or multiple
-
DiagnosisA) Clinically B) Laboratory AC Tap (0.1ml) Vitreous tap
(0.2 ml) Standard Media Grams stain Blood agar ( most aerobic
bacteria) Giemsa stain Chocolate (aerobic , Neisssseria ,
Haemophilus ) Culture Thioglycolate broth ( aerobic ,anaerobic
bacteria) SDA ( fungi) Specialized Media Lowenstein Jensen (
mycobacterium , nocardia) Non- nutrient agar E.coli enriched
PCR
-
Ancillary studies1) Ultrasound-vitreous membrane and opacities
anatomical status of the retina extent of inflammation choroidal
detachment IOFB presence and localization retained lens
material
2) CT Scan not much useful to detect IOFB3) ERG grossly abnormal
- poor prognosis slightly subnormal - slight better
-
For endogenous endoph.:Complete blood count ( signs of
infection)ESR ( malignancy ,chronic infections, rheumatic
diseases)Cultures ( for detection of source of infection) blood
culture urine culture throat swab CSF stool indwelling catheters
tipChest X-rayOther necessary investigation according to suspicion
like HIV
-
TreatmentGOALS
1) Retention of useful vision.2) Minimize the infection with
antimicrobial agents.3) Limit the inflammation. 4) Symptomatic
relief.
-
For bacterial endoph.Prompt therapy is critical Modalities
MEDICAL 1) Antibiotics Intravitreal, periocular, topical ,
systemic 2) Anti-inflammatory (steroids) topical ,periocular ,
systemic ( not for chronic Endophthalmitis) 3) Supportive
Cycloplegic,AGM
SURGICAL vitrectomy
-
Medical treatmentIntravitreal injection - preferred route in all
types of endophthalmitis. - direct administration in vitreous - by
passes Blood Ocular Barrier. Intravitreal injection Vancomycin (
1.0 mg in 0.1 ml ) Amikacin ( 400ug in 0.1 ml) OrCeftazidime
(2.25mg/0.1ml)Subconjunctival injections Vancomycin (25mg in
0.5ml)Amikacin (25mg in 0.5ml)
-
Systemic : 1) penetrating ocular injury from contaminated
objects. 2) Endogenous bacterial endophthalmitis. For Post-Op
Endophthalmitis: - no role due to MIC in vitreous -Quinolones (
ciprofloxacin) can be tried
Rapid bacterial proliferation make even the Quinolones
concentration inadequate to prevent the growth of organisms. Ideal
duration - at least 2-4 week
-
DrugsDosesVancomycin1 gm iv.12 hrly(10-30 mg/kg)Ceftazidime2 gm
iv. BdAmikacin250 mg iv. Tid(15mg/kg)Gentamycin80 mg iv tid
(3-5mg/kg)Ciprofloxacin750 mg po.bdOfloxacin200 mg 12 hrly
-
Role Of SteroidsIndications recent onset after rule out of
fungus.Contraindication Late onset endophthalmitis fungal
endophthalmitisMechanism- reduce inflammation clinically and
histopathologicaly
limit ocular damage
Routes - Intravitreal(dexa400mgm in 0.1ml),systemic,
sub-conjuctival(1 mg in 0.25ml), topical
-
Treatment in Fungal Endoph.
Indication of Intravitreal antifungal 1) pre-existing fungal
keratitis endophthalmitis 2) fungal endogenous endophthalmitis (
culture +)
Commonly used medications intra-vitreal Amphotericin B-
5microgm/0.1ml oral fluconazole / ketoconazole ( better vitreal
penetration)
Voriconazole Intravitreal -50 microgm/0.1ml oral- 200 mg bd
intravenous- 6 mg/kg bd 2 doses
Steroids in any form C/I
-
Systemic antifungals
-
VitrectomyAdvantages ( DIAGNOSTIC / THERAPEUTIC)1) more material
for culture esp. fungus.
2) removal of inflammatory mediators /organisms /toxins.
3) removal of source of infection.
4) better dispersion of antibiotics in the vitreous.5) clears
the media and better posterior segment visualization
6) removes vitreous membrane which may be a source of late
traction and subsequent detachment. guided by Endophthalmitis
vitrectomy study (EVS)
-
Endophthalmitis Vitrectomy Study(EVS)Multicenter randomized
trial carried out at 24 centres in U.S. (1990-1994)Purpose : To
determine The role of IV antibiotics in the management of POERole
of initial vitrectomy in management.Patients : N = 420 patients
having clinical evidence of POE within 6 weeks of cataract
surgeryInterventionRandom assignment to immediate vitrectomy (VIT)
or vitreous biopsy (TAP). They were also randomly assigned to
treatment with IV or no IV.
-
Study medications : After initial VIT or TAP, all patients
received I/V injection of amikacin (0.4 mg) + vanco(1 mg)Vanco(25
mg in 0.5 ml), Ceftazidime (100 mg in 0.5 ml), Dexamethasone (6 mg
in 0.25 ml) administered subconjunctivally. IV treatment:
ceftazidime (2 g every 8 hrs) + amikacin (6mg/kg every 12 hrs) for
5-10 days
-
Main outcome measuresEvaluation of visual acuity and clarity of
ocular media at 3, 9, 12 monthsNo difference in outcome between PPV
followed by I/V group compared to vitreous tap and I/V if vision
better than light perceptionNo difference in final visual acuity or
media clarity whether or not EVS systemic antibiotic( Amikacin ,
Ceftazidime) were employedVision with light perception or worse
,much better results in immediate PPV
-
Limitations of EVS 1) only for acute post -operative
endophthalmitis after cataract surgery 2) doesnt mention the
outcome of vitrectomy in other forms of endophthalmitis like; -
post traumatic -chronic post operative etc -endogenous
endophthalmitis
-
ComplicationsRetinal necrosis Retinal detachment Retinal
necrosis Vitreous tap VitrectomyIncreased intraocular pressure
Retinal vascular occlusion Optic neuropathy Panophthalmitis
Hypotony Ciliary body shut down Leaking wound Retinal detachment
Cyclodialysis cleft Medication
-
Prevention1 ) PRE-OPERATIVE a) preexisting conditions
e.g.blepharitis, conjunctivitis , dacryocyctitis,, infected contra-
lateral socket
b) povidone iodine ( BETADINE) drops
c) meticulous draping
d) topical antibiotic 2) INTRA-OPERATIVE irrigation of A/C with
vancomycin3) POST OPERTAIVE anterior sub-tenon antibiotic / sub
conj. antibiotic
-
Bleb related 1) early diagnosis and treatment of conjunctivitis.
2) wearing of contact lens should be discouraged. 3) treatment of
associated periocular infections.Traumatic 1) safety goggles. 2)
timely and appropriate management of ocular trauma.Endogenous 1)
adequate and timely management of systemic illness. 2) intravenous
drug abuse reduction. 3) control of all predisposing factors.
-
Toxic anterior segment syndromeacute, sterile postoperative
anterior segment inflammation following any anterior segment
surgery which is sterile/noninfectiouscaused by a substance that
enters the anterior segment either during or immediately after
surgery, resulting in toxic damage to intraocular tissuesSymptoms:
blurred vision(MC),pain usually
minimal/absent,rednessSigns:limbus-to-limbusdiffuse corneal edema,
marked A/S inflammation-hypopyon,fibrin
-
May damage to iris which can cause a permanently
dilated/irregular pupil with thinning of iris stromaMay have
associated trabecular meshwork damage which can lead to secondary
glaucomaHow to differentiate from infectious endophthalmitis:signs
appearing within the first 1248hSymptoms:no painSigns:diffuse
corneal edemaGood response to steroids
-
Reasons and Indications for Antimicrobial Susceptibility Testing
(AST)GoalOffer guidance to physician in selecting effective
antibacterial therapy for a pathogen in a specific body
sitePerformed on bacteria isolated from clinical specimens if the
bacterias susceptibility to particular antimicrobial agents is
uncertain
Susceptibilities NOT performed on bacteria that are predictably
susceptible to antimicrobials
Ex. Group A StrepDr.Sadaf Konain Ansari
-
Selecting Antimicrobial Agents for Testing and ReportingClinical
& Laboratory Standards Institute (CLSI)Develop standards,
methods, QC parameters, and interpretive criteria for sensitivity
testingIf necessary, can alter the breakpoints of the SIR (
susceptible, intermediate, resistant) based on emerging
resistance
Dr.Sadaf Konain Ansari
-
Selecting Antimicrobial Agents for Testing and Reporting
(contd)There are approximately 50 antibacterial agentsFollow CLSI
recommendationsEach laboratory should have a battery of antibiotics
ordinarily used for testingDrug formulary decided by medical staff,
pharmacists, and medical technologists Dr.Sadaf Konain Ansari
-
Selection of Test BatteriesGenerally, labs choose 10-15
antibiotics to test susceptibility for GP organisms and another
10-15 for GN organismsToo many choices can confuse physicians and
be too expensivePrimary objectiveUse the least toxic, most
cost-effective, and most clinically appropriate agentsRefrain from
more costly, broader-spectrum agents
Dr.Sadaf Konain Ansari
-
Example of Drug FormularyDr.Sadaf Konain Ansari
DrugEnterococcusStaphylococcus
spp.AmpicillinXCefazolinXClindamycinErythromycinXLinezolidXXOxacillinXPenicillin
GXXRifampinXStreptomycin-2000XTetracyclineXXTrimeth/
SulfaXVancomycinXX
-
Example of Drug FormularyDr.Sadaf Konain Ansari
DrugEnterobacteriaceaePs. aeruginosaAmpicillinXPiperacillin/
Tazo.XXCefepimeXXImipenemXXGentamycinXXTobramycinXXCiprofoxacinXXLevofloxacinXXNitrofurantoinXTrimethoprim/SulfaX
-
DefinitionsMinimum inhibitory concentration(MIC)Lowest
concentration of an antimicrobial agent that visibly inhibits the
growth of the organism.
Minimum bactericidal concentration (MBC)Lowest concentration of
the antimicrobial agent that results in the death of the
organism.Dr.Sadaf Konain Ansari
-
Definitions (contd)Susceptible SInterpretive category that
indicates an organism is inhibited by the recommended dose, at the
infection site, of an antimicrobial agentIntermediate IInterpretive
category that represents an organism that may require a higher dose
of antibiotic for a longer period of time to be inhibitedResistant
RInterpretive category that indicates an organism is not inhibited
by the recommended dose, at the infection site, of an antimicrobial
agent.Dr.Sadaf Konain Ansari
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Methods of Performing ASTAgar dilution methodBroth macrodilution
/ Tube dilutionBroth microdilutionDisk diffusion methodGradient
diffusion method (E-Test)Dr.Sadaf Konain Ansari
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Standardization of Antimicrobial Susceptibility TestingInoculum
PreparationUse 4-5 colonies NOT just 1 colonyInoculum
Standardizationusing 0.5 McFarland standardDr.Sadaf Konain
Ansari
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Methods of Performing ASTAgar DilutionDilutions of antimicrobial
agent added to agarGrowth on agar indicates MICBroth
macrodilution/Tube Dilution TestsTwo-fold serial dilution series,
each with 1-2 mL of antimicrobial Too expensive and time
consumingMicrodilution Testsplastic trays with dilutions of
antimicrobialsDr.Sadaf Konain Ansari
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Disk Diffusion/ Kirby- BauerProcedureUse a well-isolated, 18-24
hour old organismTransfer organism to a brothEither tryptic
soy/sterile salineEnsure a turbidity of 0.5 McFarlandInoculate MH
agar by swabbing in three different directions Lawn of growth Place
filter paper disks impregnated with anitmicrobial agents on the
agarInvert and incubate for 16-18 hours at35 oC in non-CO2 Dr.Sadaf
Konain Ansari
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Disk Diffusion/ Kirby-Bauer (contd)During incubation, drug
diffuses into agarDepending on the organism and drug, areas of no
growth form a zone of inhibitionZones are measured to determine
whether the organism is susceptible, intermediate, or resistant to
the drugDr.Sadaf Konain Ansari
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E- test/ Gradient Diffusion MethodMIC on a stickPlastic strips
impregnated with antimicrobial on one sideMIC scale on the other
sideRead MIC where zone of inhibition intersects E strip
scaleDr.Sadaf Konain Ansari
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Automated Antimicrobial Susceptibility Test Methods
Detect growth in micro volumes of broth with various dilutions
of antimicrobialsDetection via photometric, turbi-dimetric, or
fluoro-metric methodsTypesBD PhoenixMicroscan WalkawayTREK
SensititreVitek 1 and 2
Dr.Sadaf Konain Ansari
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Automated Antimicrobial Susceptibility Test Methods
AdvantagesIncreased reproducibilityDecreased labor costsRapid
resultsSoftwareDetects multi-drug resistancesESBLsCorrelates
bacterial ID with sensitivityDisadvantagesCostDr.Sadaf Konain
Ansari
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Quality Control in Susceptibility TestingReflects types of
patient isolates & range of susceptibilityFrequency of quality
control depends on method, CLSI, or manufacturerReference strains
of QC materialAmerican Type Culture Collection(ATCC) E. coli ATCC*
25922S. aureus ATCC* 25923
Dr.Sadaf Konain Ansari
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The Superbugs (important to remember)Organisms resistant to
previously effective drugsMRSA methicillin-resistant Staphylococcus
aureusmecA gene codes for a PBP that does not bind beta-lactam
antibioticsResistant to oxacillinVancomycinVRE Enterococcus
speciesVISA/VRSA- Staphylococcus aureus
Dr.Sadaf Konain Ansari
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The Superbugs: The Beta-Lactamases
Gram negative rods that have genes on chromosomes that code for
enzymes against certain antimicrobialsESBLs-extended spectrum beta
lactamaseResistant to extended spectrum cephalosporins,
penicillins, aztreonamExamples: E. coli, KlebsiellaCarbapenemases
(CRE)Klebsiella pneumoniae- KPC- Class AClass B (NDM, VIM, IMP)-
metallo beta lactamasesResistant to penicillins, cephalosporins,
carbapenems, and aztreonamCephalosporinasesAmpC
enzymeinducibleSPACE organismsDr.Sadaf Konain Ansari
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Controlling the SuperbugsLabs RoleRecognize and report isolates
recovered from clinical specimensMethods for identification include
automated systems and screening agars
Dr.Sadaf Konain Ansari
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Controlling the SuperbugsRole of Health Care
Workers/FacilitiesHand hygiene with the use of alcohol-based hand
rubs or soap and water after patient careContact precautions for
patients identified as colonized or infected with a
superbugHealthcare personnel education about the methods of
transmission, contact precautions, and proper use of hand hygiene
Minimization of invasive devices (catheters, etc.)Proper
administration of antimicrobial agents where therapy is selected
for susceptible organisms for the proper duration
Dr.Sadaf Konain Ansari
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Dr.Sadaf Konain AnsariContinue
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Referenceshttp://www.biomerieux-diagnostics.com/servlet/srt/bio/clinical-diagnostics/dynPage?doc=CNL_CLN_PRD_G_PRD_CLN_22http://www.cdc.gov/std/gonorrhea/lab/diskdiff.htmhttp://www.who.int/drugresistance/Antimicrobial_Detection/en/index.htmlKiser,
K. M., Payne, W. C., & Taff, T. A. (2011). Clinical Laboratory
Microbiology: A Practical Approach . Upper Saddle River, NJ:
Pearson Education.Mahon, C. R., Lehman, D. C., & Manuselis, G.
(2011). Textbook of Diagnostic Microbiology (4th ed.). Maryland
Heights, MO: Saunders.Murray, P. R. (2013,May).
Carbapenem-resistant Enterobacteriaceae: what has happened, and
what is being done. MLO, 45(5), 26-30.Dr.Sadaf Konain Ansari
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Dr.Sadaf Konain AnsariExercise Questions
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ESKAPEPathogens of Highest Concern The most serious, life-
threatening infections are caused by a group of drug- resistant
bacteria that the Infectious Diseases Society of America (IDSA) has
labeled the "ESKAPE" pathogens, because they effectively escape the
effects of antibacterial drugsWhat are ESKAPEDr.Sadaf Konain
Ansari
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Minimum inhibitory concentration(MIC)Lowest concentration of an
antimicrobial agent that visibly inhibits the growth of the
organism.
Minimum bactericidal concentration (MBC)Lowest concentration of
the antimicrobial agent that results in the death of the
organism.What stand for MIS, and MBC?Dr.Sadaf Konain AnsariCommon
Questions:
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Susceptible SInterpretive category that indicates an organism is
inhibited by the recommended dose, at the infection site, of an
antimicrobial agentIntermediate IInterpretive category that
represents an organism that may require a higher dose of antibiotic
for a longer period of time to be inhibitedResistant RInterpretive
category that indicates an organism is not inhibited by the
recommended dose, at the infection site, of an antimicrobial
agent.What stands for S, I and R?Dr.Sadaf Konain AnsariCommon
Questions:
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THANK YOUEmail:[email protected]
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