POSTULATED RISK FACTORS FOR AMD

• Ageing
– The Framingham Eye study (1976) showed the prevalence
– 65-74 years- 11%
– 75-85 years- 28%
• Gender
– Blue 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.  

POSTULATED RISK FACTORS FOR AMD
• Cardiovascular Risk factors
– Hypertension: Rotterdam study (2003)
suggests positive correlation between high
blood pressure and increased incidence of
AMD.
• Light
– Initially 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
• Nutrition
– Several 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
Oestrogen
– The use of exogenous
supplements in post menopausal
women lowered risk of AMD in a
study performed by the Eye
Case Control Study Group.

6p21. 2007 Mar. *Moshfeghi DM. Retina.GENETICS • Family history of macular degeneration: – Autosomal dominant with variable penetration – In first degree relative with macular degeneration.5 times if one has the CFH gene variant. chances is about 2. • 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 1q32.27(3):269-75 .5 to 5. and 10q26 are the risk for development of AMD – The odds of developing macular degeneration are increased by about 2.5 times. Blumenkranz MS.

AMD: SYMPTOMS Initial 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 .

driving are greatly impaired.AMD: SYMPTOMS • Patient’s ability to perform normal daily tasks such as reading. sewing. telling the time. .

MACULA: ANATOMY MACULA Foveola Fovea Umbo Para-foveal zone Peri-foveal zone .

Phagocytosis and regeneration of visual pigment .RETINAL PIGMENT EPITHELIUM The retinal pigment epithelium (RPE) is a single layer of hexagonally shaped cells & attached to the photoreceptor layer.Formation of the outer blood retinal barrier 4. Functions 1.Maintain the photoreceptors 2.Absorption of stray light 3.

• Bruch’s membrane separates the RPE from vascular choroid. • Function of Bruch’s 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 AMD • • Accounts for about 90% of all cases Also 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 AMD Drusen .

DRY AMD 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 lost .

DRY AMD Drusen: • Drusen are aggregation of hyaline material located between Bruch’s membrane and RPE. • Drusen are composed of metabolic waste products from photoreceptors. . • Hypo/hyper pigmentation of RPE may be present.

• Types: – Small: <63 µ – Intermediate: 63-124 µ – Large: >125 µ – Hard: • generally small (<63 µ). fluffy margins • High risk for neovascular AMD . solid appearing drusen with well defined margins • may be asymptomatic – Soft: • larger (>63 µ). ill defined. pale yellow. bright yellow.

• Soft Drusen: – Membranous: • 63-175 µ • Pale. shallow appearing drusens – Granular: • About 250 µ • Solid appearing drusens – Serous: • • • • >500 µ Have pooled serous fluid blister like appearance May result in serous PED .

HISTOPATHOLOGY • Drusen appear as focal areas of the eosinophilic material between the basement membrane of RPE & BM. Drusen . • 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.

hard drusen) – Visual acuity (VA) is not a criterion for the diagnosis *International Epidemiological Age-related Maculopathy study Group .• Diagnostic criteria* • Degenerative disorder in persons >50 years.areas of hypo/hyperpigmentation (excluding pigment surrounding small. characterized by the presence of any of the following: – Soft drusen (>63 µ) – RPE abnormalities.

DRY AMD .

DRUSEN .

GEOGRAPHIC ATROPHY .

• Geographic atrophy. RPE atrophy >175 microns with exposure of the underlying choroidal vessels. but require additional magnification of the text and more intense lighting to read small points.severest form of the dry AMD. • Presence of large drusen (>63 microns in diameter) is associated with a risk of the late form of the disease like CNV.DRY AMD: COURSE AND VISUAL PROGNOSIS • Patients with only drusen not have much loss of vision. .

• Age related Bruch’s membrane change may be especially important in exudative macular degeneration. drusen and other metabolic accuminata such as lipids and loss of basal connections with the RPE. • Pigment epithelial detachment may occur in relation to Bruch’s membrane change. this change includes thickening of Bruch’s membrane.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. .

WET AMD Photoreceptors and pigment epithelium send a distress signal to choriocapillaries to make new vessels New vessels grow behind the macula Breakdown in the Bruch’s membrane Blood vessels are fragile Leak blood and fluid Scarring of macula Potential for rapid and severe visual damage .

WET AMD .

. 2008 Dec. characterized by the presence of any of the following: – choroidal neovascularization – serous retinal pigment epithelial detachment – hemorrhagic retinal pigment epithelial detachment – fibrotic scar in the macula *Takahashi K et al.WET AMD • Diagnostic criteria* • persons >50 years.112(12):1076-84.Nihon Ganka Gakkai Zasshi.

WET AMD .

WET AMD .

Extrafoveal: >200 µm & <2500 µm from the centre of FAZ • Types: – – Type I: CNV beneath RPE Type II: CNV above RPE . • Lesion location is classified angiograpically as follows:1. Juxtafoveal: 1-199 µm from the centre of FAZ 3.WET AMD • CNV lesion is well demarcated & its location may be determined by closest point to the FAZ. Subfoveal: under the centre of FAZ 2.

.

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:



Drusenoid
Serous
Fibro vascular
Hemorrhagic

RPE DETACHMENT (PED)

• 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. .RPE TEAR • Spontaneously or on photocoagulation of CNV.

DISCIFORM SCAR .

. • Once CNV has developed in one eye. visual acuity deteriorates more slowly and stabilizes within 3 years. • More frequently. • Patients with CNV shows rapid decline in vision (20/200) within weeks.WET AMD: COURSE AND VISUAL PROGNOSIS • Leakage of blood or serum in CNV may occur precipitously and associated with the abrupt loss of vision. the other eye is at relatively high risk for the same change.

AMD: STAGING • AREDS Categories: – No AMD (AREDS category 1) • No or a few small (<63 micrometres in diameter) drusen. or macular pigmentary changes. or dry. or geographic atrophy not involving the foveal centre. serous retinal or retinal pigment epithelium detachments. – Early AMD (AREDS category 2) • Many small drusen or a few intermediate-sized (63-124 micrometres in diameter) drusen. – Intermediate AMD (AREDS category 3) • Extensive intermediate drusen or at least one large ( ≥125 micrometres) drusen. AMD) • Choroidal neovascularisation (wet AMD) • evidence for neovascular maculopathy (subretinal haemorrhage. . lipid exudates. or fibrovascular scar). – Advanced AMD (AREDS category 4) • Geographic atrophy involving the foveal centre (atrophic.

• Ophthalmoscopy: to detect drusen. as well as neovascularization • Fluorescein and ICG angiography: Determines the presence and location of neovascularization. • Aided by optical coherence tomography.AMD: DIAGNOSTIC TOOLS • Visual acuity • Amsler grid test: Assesses distorted or reduced vision and small irregularities in the central field of vision. .

AMD: MANAGEMENT • Role of Antioxidants: • AREDS-1 study.A 25000 IU) – Zinc: 80 mg – Copper (cupric oxide): 2 mg . • 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.use of high dose of multivitamins & antioxidants decreases the risk of progression of ARM in those with high risk characteristics.

AMD: MANAGEMENT • AREDS-2 Study: – Lutein & zeaxanthin antioxidants micronutrients found in human macula. – omega-3 fatty acids.400 IU Beta-Carotene . docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have also been shown to help with AMD.2 mg DHA .650 mg . – Diet rich in these give some protection against the disease.15 mg Zinc .80 mg Copper .10 mg Zeaxanthin .2 mg Lutein .500 mg Vitamin E .350 mg EPA . – AREDS-2 Formula• • • • • • • • • Vitamin C .

Antiangiogenic drugs 2. Laser photocoagulation .AMD: MANAGEMENT • Current treatment – 1. Photodynamic therapy 3.

• • • • Bevacizumab (Avastin) Ranibizumab (Lucentis) Pegaptanib sodium (Macugen) Aflibercept (VEGF Trap-Eye) .ANTI ANGIOGENICS • Anti-VEGFs: – reduce the growth of new blood vessels. decrease the leakage through them.

metastatic breast and non-small cell carcinoma of lung – Is being used off-label for choroidal neovascularization based on results of short-term studies – Dose. repeated 6-8 weekly.25 mg. use in metastatic colorectal.v.• Bevacizumab (Avastin)– Full-length monoclonal antibody (150 kD) – Binds all isoforms of VEGF – Has FDA approval for i.1-1. .

antibody fragment (Fab) (48 kD) – Binds to all isoforms of VEGF. kappa isotype. – Dose.05 mL) four weekly & further on physician's assessment.• Ranibizumab (Lucentis ) – Recombinant humanized immunoglobulin G1.5 mg (0. • Comparison of AMD Treatment Trials (CATT) – Multicentre clinical trial – Compare safety and efficacy of ranibizumab and bevacizumab – Currently under way .First 3 injections of 0.

.189 and 206 isoforms – Given 0.• Pegaptanib sodium (Macugen) – 28 base ribonucleotide aptamer – Binds to Heparin-binding domain of VEGF-A – Inactivates VEGF-A 165.3 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-A – Also blocks placental growth factors-1 and 2 – Two Phase III clinical trials (VIEW-1 and VIEW-2) comparing aflibercept to ranibizumab are currently ongoing.

COMPLICATIONS • Common- – Raised intra-ocular pressure • Occasional – Cataract Formation – Intra-ocular hemorrhage • Rare – Endophthalmitis – Retinal Detachment .

SURGICAL OPTIONS • • • • Submacular excision of CNV Macular translocation Retinal rotation Homologous Iris/Retinal pigment epithelium transplantation • Autologous RPE transplantation .

visionrobbing blood vessels under the retina. – safety and efficacy established in a Phase II study – Phase III clinical trial is planned . • siRNA (Bevasiranib) – silences the genes that lead to the growth of unhealthy. • AdPEDF : Adenovirus-based Pigment Epithelium Derived Factor – a gene that leads to the production of the protein PEDF.EMERGING TREATMENTS FOR AMD • Retaane® (Anecortave acetate) – modified steroid promising in reducing the risk of vision loss due to the growth of unhealthy blood vessels in wet AMD. thereby preserving vision. which helps keep photoreceptors healthy.

) – a topical formulation that inhibits the nicotinic acetylcholine receptors – Currently undergoing phase II human study • EVIZON™ (squalamine lactate) – aminosterol with anti–angiogenic 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 eye’s natural defense system against disease and injury. – Protection against both cataract and dry AMD – currently in a clinical study for geographic atrophy (advanced dry AMD) .EMERGING TREATMENTS FOR AMD • ATG3 (mecamylamine) (Contd.

) • Encapsulated Cell Technology (ECT) – Developed by Neurotech.EMERGING TREATMENTS FOR AMD (Contd. – tiny capsule (6 mm) implanted into the eye. preserving vision. contains retinal cells that produce a vision-preserving protein . . – currently in a Phase II human clinical trial for people with dry AMD.Ciliary Neurotrophic Factor (CNTF) – keep photoreceptors alive and healthy.

– Closed circuit television & scanning devises are also available to provide electronic magnification & contrast enhancement. – Reading lamps & simple magnifiers may be beneficial.REHABILATATION • Low vision aids– Individual who experiences untreatable visual loss & effects the daily life. .

CLASSIFICATION • Endophthalmitis can be classified according to the • Infectivity – Infective / non infective ( sterile) • Mode of entry – exogenous / endogenous • Type of etiological agent .

Classification Infectious Exogenous Post –trauma (PEI-IOFB) Sterile (Infectivity) Endogenous ( Mode of entry) Post-operative Fulminant Acute Blebitis Chronic .

Cont. • Etiological agent Endophthalmitis Bacterial Fungal viral Parasitic 57 .

.Gram positive bacteria 75%-85% Gram negative bacteria 10%-15% Fungi 3% Staphylococcus epidemidis (43%) Pseudomonas (8%) Aspergillus Streptococcus spp (20%) Proteus (5%) Fusarium Staphylococcus aureus Haemophilus (15%) influenzae (1%) Propionibacterium acnes Klebsiella( 0-1%) Bacillus cereus (1%) Coliform spp (0-1%) Cephalosporium spp.

Exogenous Endophthalmitis • Vitreous 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 exterior • Maily bacterial .

12% 0.18% 0.37% 0.06% .3% PPV 0.11% Glaucoma filtration surgery 0.1)Post-op Endophthalmitis Incidence: 0.072% Secondary PCIOL 0.05% MC among all types: 49-76% Surgery Bascom Palmer Eye Institute (1984-1994) Katten et al (1984-1989) ECCE with and without PCIOL 0.05% PK 0.08% 0.05% 0.

air condition in O. Lacrimal sac nasal mucosa.lid margin and lashes conjuctival sac. gloves. IOL Clinical Importance. drops and ointment skin antiseptic. corneal graft Objects and materials surgical instruments.Source of infection Airborne respiratory origin.all causes are preventable .T Solution and medications irrigating solutions. masks. viscoelastic and silicon oil Tissue periocular skin .

Risk Factors Preoperative risk factors blepharitis . contaminated eye drops.prolonged surgery & contaminated irrigation solutions . PC rent .vitreous loss . active conjunctivitis Lacrimal drainage system infection or obstruction . Operative risk factors wound abnormalities.

acne related fungi S.epidermidis -staph.aureus -coag.epidermids .Types Of Presentations • • Fulminant Acute Chronic (<4 days) (4-7days) (>4 weeks) -gram –ve -staph.-ve cocci -streptococci delayed delayed entry onset bleb P.

.

2)Post traumatic



Incidence-2-7%(unsterile conditions & contaminated objects)
Contributes to 17-40% of all cases
Penetrating ocular trauma is main culprit
Causative organisms

fulminant:
B. cereus
Streptococcus

acute:
chronic:
S.epidermidis(MC) fungi:
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 endophthalmitis





4-18% of all cases
After glaucoma filtration surgery
May occur at any time (months- years )after surgery
Most of the time through intact bleb via conjuctival flora
Poor prognosis as org. are more virulent
Causative organism
streptococci(MC)-faecalis,viridans,pneumoniae
H.influenzae
staph. are rare
• Clinical signs
infected white bleb
Vitritis
Hypopyon

.

low virulence organism .conjunctivitis.mild intraocular inflammation .• Risk factors: use of antimitotic agents.inferior blebs.no Vitritis .periocular infections • Should be differentiated from BLEBITIS • Blebitis .contact lens.

prolong indwelling catheter ( intravenous .Endogenous(Metastatic) Endophthalmitis • 2-15% of all cases • Hematogenous spread of organism from distant source • Retina and choroid primarily involved due to high vascularity.Diabetes .recent major abdominal surgery . • Fungi> bacteria Candida(MC)>Aspergillus • Predisposing factors . septicemia etc) • no structural defect in globe .immunosuppresion(AIDS. meningitis.intravenous drug abuser . TPN) .distant infection ( endocarditis.malignancies medications) .

Clinical Approach Symptoms: Decreased or blurred vision ( sudden / severe – acute) ( slowly / mild—chronic) Pain Photophobia Redness of eyes Swollen eyelids Discharge White lesion in black part of the eye Floaters Fever .

resistant to dilatation.post. flare . DM folds keratic precipitate.Signs • Initial visual acuity ( prognostic significance) • Ocular motility ( sign of orbital inflammation) • Eyelid swollen . opacification . blepharospasm • Conjunctiva hyperemia. infiltrates. occult penetration • Anterior chamber cells. fibrinous exudates and Hypopyon • Iris – muddy.boggy. bleb examination if present • Cornea edematous. chemosis.synechiae .

usually low.• • • • Pupil-absent or sluggish reaction to light Lens . exudates around IOL Vitreous .Membrane .may be high in early cases • Signs of penetrating injury and Intraocular foreign body • Wound dehiscence . yellowish appearance Fundus examination Absent red reflex and no fundal view Amaurotic cat’s eye reflex Papilitis White lesion in retina and chorioid Retinal hemorrhage and periphlebitis • IOP.Vitritis . exudates .

• OCULAR MEDIA CLARITY (I/O) Grade 1.Faint outline of Disc visible.Red reflex absent. Grade 3. can visualize second order retinal vessels. 6/12 view of the retina. Grade 4.Cont.Can see only 1st order vessels.Media clarity <6/12. . Grade 5. Grade 2.Media clarity. red reflex present.

.

mild external ocular involvement • Progressive iridocyclitis.endogenous endophthalmitis in immunocompromised patients • Minimal pain.Fungal Endophthalmitis Caused by – Candida albicans. Aspergillus. • Causes . Vitritis ( string of pearl ) • Yellow white choroidal lesion single or multiple . Fusarium etc.delayed post-operative endophthalmitis .

nutrient agar E. nocardia) Non.coli enriched PCR . Neisssseria .Diagnosis • A) Clinically • B) Laboratory AC Tap (0.1ml) Vitreous tap (0.anaerobic bacteria) SDA ( fungi) Specialized Media Lowenstein –Jensen ( mycobacterium .2 ml) Standard Media Gram’s stain Blood agar ( most aerobic bacteria) Giemsa stain Chocolate (aerobic . Haemophilus ) Culture Thioglycolate broth ( aerobic .

slight better .poor prognosis slightly subnormal .• Ancillary studies 1) 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 IOFB 3) ERG grossly abnormal .

chronic infections.: Complete blood count ( signs of infection) ESR ( malignancy . rheumatic diseases) Cultures ( for detection of source of infection) blood culture urine culture throat swab CSF stool indwelling catheter’s tip Chest X-ray Other necessary investigation according to suspicion like HIV .For endogenous endoph.

.Treatment GOALS 1) Retention of useful vision. 3) Limit the inflammation. 2) Minimize the infection with antimicrobial agents. 4) Symptomatic relief.

periocular . topical . • Prompt therapy is critical • Modalities MEDICAL SURGICAL 1) Antibiotics Intravitreal. systemic 2) Anti-inflammatory (steroids) topical . periocular.AGM vitrectomy .For bacterial endoph. systemic ( not for chronic Endophthalmitis) 3) Supportive – Cycloplegic.

5ml) (25mg in 0.preferred route in all types of endophthalmitis. .5ml) (2.0 mg in 0.1ml) Subconjunctival injections .1 ml ) ( 400ug in 0.25mg/0.1 ml) – Vancomycin – Amikacin (25mg in 0.Medical treatment • Intravitreal injection .by passes Blood Ocular Barrier.direct administration in vitreous . Intravitreal injection – Vancomycin – Amikacin Or – Ceftazidime ( 1.

• Systemic : 1) penetrating ocular injury from contaminated objects. Ideal duration .at least 2-4 week .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. 2) Endogenous bacterial endophthalmitis. • For Post-Op Endophthalmitis: .

Tid (15mg/kg) Gentamycin 80 mg iv tid (3-5mg/kg) Ciprofloxacin 750 mg po. Bd Amikacin 250 mg iv.Drugs Doses Vancomycin 1 gm iv.bd Ofloxacin 200 mg 12 hrly .12 hrly (10-30 mg/kg) Ceftazidime 2 gm iv.

systemic.Intravitreal(dexa400mgm in 0. Contraindication Late onset endophthalmitis fungal endophthalmitis Mechanism.Role Of Steroids Indications recent onset after rule out of fungus. topical . subconjuctival(1 mg in 0.1ml).25ml).reduce inflammation clinically and histopathologicaly limit ocular damage Routes .

1ml oral.200 mg bd intravenous.6 mg/kg bd 2 doses • Steroids in any form C/I . • Indication of Intravitreal antifungal 1) pre-existing fungal keratitis endophthalmitis 2) fungal endogenous endophthalmitis ( culture +) • Commonly used medications intra-vitreal Amphotericin B.5microgm/0.Treatment in Fungal Endoph.1ml oral fluconazole / ketoconazole ( better vitreal penetration) • Voriconazole Intravitreal -50 microgm/0.

Systemic antifungals .

fungus. • 3) removal of source of infection. • 4) better dispersion of antibiotics in the vitreous . • 2) removal of inflammatory mediators /organisms /toxins. guided by Endophthalmitis vitrectomy study (EVS) .Vitrectomy Advantages ( DIAGNOSTIC / THERAPEUTIC) • 1) more material for culture esp. • 5) clears the media and better posterior segment visualization • 6) removes vitreous membrane which may be a source of late traction and subsequent detachment.

They were also randomly assigned to treatment with IV or no IV.S. (1990-1994) Purpose : To determine • The role of IV antibiotics in the management of POE • Role of initial vitrectomy in management. . Patients : N = 420 patients having clinical evidence of POE within 6 weeks of cataract surgery Intervention Random assignment to immediate vitrectomy (VIT) or vitreous biopsy (TAP).Endophthalmitis Vitrectomy Study(EVS) • Multicenter randomized trial carried out at 24 centres in U.

• IV treatment: ceftazidime (2 g every 8 hrs) + amikacin (6mg/kg every 12 hrs) for 5-10 days . • Dexamethasone (6 mg in 0.4 mg) + vanco(1 mg) • Vanco(25 mg in 0.25 ml) administered subconjunctivally. all patients received I/V injection of amikacin (0.Study medications : After initial VIT or TAP.5 ml).5 ml). Ceftazidime (100 mg in 0.

much better results in immediate PPV .Main outcome measures • Evaluation of visual acuity and clarity of ocular media at 3. 9. 12 months • No difference in outcome between PPV followed by I/V group compared to vitreous tap and I/V if vision better than light perception • No difference in final visual acuity or media clarity whether or not EVS systemic antibiotic( Amikacin . Ceftazidime) were employed • Vision with light perception or worse .

post –traumatic -chronic post operative etc -endogenous endophthalmitis .• Limitations of EVS 1) only for acute post -operative endophthalmitis after cataract surgery 2) doesn’t mention the outcome of vitrectomy in other forms of endophthalmitis like. .

Complications • • Retinal necrosis Retinal detachment – Retinal necrosis – Vitreous tap – Vitrectomy • • • • • Increased intraocular pressure Retinal vascular occlusion Optic neuropathy Panophthalmitis Hypotony – – – – – Ciliary body shut down Leaking wound Retinal detachment Cyclodialysis cleft Medication .

. dacryocyctitis. antibiotic .Prevention 1 ) PRE-OPERATIVE a) preexisting conditions e.blepharitis.g.lateral socket b) povidone iodine ( BETADINE) drops c) meticulous draping d) topical antibiotic 2) INTRA-OPERATIVE irrigation of A/C with vancomycin 3) POST –OPERTAIVE anterior sub-tenon antibiotic / sub conj. infected contra. conjunctivitis .

2) timely and appropriate management of ocular trauma. . 2) wearing of contact lens should be discouraged. Traumatic 1) safety goggles. 2) intravenous drug abuse reduction. 3) treatment of associated periocular infections. Endogenous 1) adequate and timely management of systemic illness.Bleb related 1) early diagnosis and treatment of conjunctivitis. 3) control of all predisposing factors.

pain usually minimal/absent. sterile postoperative anterior segment inflammation following any anterior segment surgery which is sterile/noninfectious • caused by a substance that enters the anterior segment either during or immediately after surgery. resulting in toxic damage to intraocular tissues • Symptoms: blurred vision(MC). marked A/S inflammation-hypopyon.redness • Signs:“limbus-to-limbus”diffuse corneal edema.fibrin .Toxic anterior segment syndrome • acute.

• May damage to iris which can cause a permanently dilated/irregular pupil with thinning of iris stroma • May have associated trabecular meshwork damage which can lead to secondary glaucoma How to differentiate from infectious endophthalmitis: • signs appearing within the first 12–48h • Symptoms:no pain • Signs:diffuse corneal edema • Good response to steroids .

Sadaf Konain Ansari .Reasons and Indications for Antimicrobial Susceptibility Testing (AST)  Goal  Offer guidance to physician in selecting effective antibacterial therapy for a pathogen in a specific body site  Performed on bacteria isolated from clinical specimens if the bacteria’s susceptibility to particular antimicrobial agents is uncertain  Susceptibilities NOT performed on bacteria that are predictably susceptible to antimicrobials  Ex. Group A Strep Dr.

resistant) based on emerging resistance Dr.Sadaf Konain Ansari . methods. QC parameters.Selecting Antimicrobial Agents for Testing and Reporting • Clinical & Laboratory Standards Institute (CLSI) – Develop standards. can alter the breakpoints of the SIR ( susceptible. intermediate. and interpretive criteria for sensitivity testing – If necessary.

Sadaf Konain Ansari . pharmacists. and medical technologists Dr.Selecting Antimicrobial Agents for Testing and Reporting (cont’d) • There are approximately 50 antibacterial agents • Follow CLSI recommendations • Each laboratory should have a battery of antibiotics ordinarily used for testing • Drug formulary decided by medical staff.

broader-spectrum agents Dr. labs choose 10-15 antibiotics to test susceptibility for GP organisms and another 10-15 for GN organisms • Too many choices can confuse physicians and be too expensive • Primary objective – Use the least toxic. and most clinically appropriate agents – Refrain from more costly. most cost-effective.Sadaf Konain Ansari .Selection of Test Batteries • Generally.

Drug
Ampicillin

Example of Drug
Enterococcus
Formulary Staphylococcus spp.
X

Cefazolin

X

Clindamycin
Erythromycin
Linezolid

X
X

Oxacillin
Penicillin G

X
X

Rifampin

X
X

Streptomycin-2000

X

Tetracycline

X

Trimeth/ Sulfa
Vancomycin

X

X
X

X

X
Dr.Sadaf Konain Ansari

Drug

Example of Drug
Formulary
Enterobacteriaceae
Ps. aeruginosa

Ampicillin

X

Piperacillin/ Tazo.

X

X

Cefepime

X

X

Imipenem

X

X

Gentamycin

X

X

Tobramycin

X

X

Ciprofoxacin

X

X

Levofloxacin

X

X

Nitrofurantoin

X

Trimethoprim/Sulfa

X
Dr.Sadaf Konain Ansari

Definitions
• 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.

Dr.Sadaf Konain Ansari

Definitions (cont’d) • Susceptible ”S” – Interpretive category that indicates an organism is inhibited by the recommended dose. at the infection site.Sadaf Konain Ansari . Dr. of an antimicrobial agent. of an antimicrobial agent • Intermediate “I” – Interpretive category that represents an organism that may require a higher dose of antibiotic for a longer period of time to be inhibited • Resistant “R” – Interpretive category that indicates an organism is not inhibited by the recommended dose. at the infection site.

Sadaf Konain Ansari .Methods of Performing AST • • • • Agar dilution method Broth macrodilution / Tube dilution Broth microdilution Disk diffusion method – Gradient diffusion method (E-Test) Dr.

Sadaf Konain Ansari .Standardization of Antimicrobial Susceptibility Testing • Inoculum Preparation – Use 4-5 colonies NOT just 1 colony • Inoculum Standardization – using 0.5 McFarland standard Dr.

Sadaf Konain Ansari .Methods of Performing AST – Agar Dilution • Dilutions of antimicrobial agent added to agar • Growth on agar indicates MIC – Broth macrodilution/Tube Dilution Tests • Two-fold serial dilution series. each with 1-2 mL of antimicrobial • Too expensive and time consuming – Microdilution Tests • plastic trays with dilutions of antimicrobials Dr.

5 McFarland – Inoculate MH agar by swabbing in three different directions “Lawn of growth” – Place filter paper disks impregnated with anitmicrobial agents on the agar – Invert and incubate for 16-18 hours at35 oC in non-CO2 Dr.Disk Diffusion/ Kirby.Bauer • Procedure – Use a well-isolated. 18-24 hour old organism – Transfer organism to a broth • Either tryptic soy/sterile saline – Ensure a turbidity of 0.Sadaf Konain Ansari .

or resistant to the drug Dr. drug diffuses into agar • Depending on the organism and drug.Sadaf Konain Ansari . intermediate.Disk Diffusion/ KirbyBauer (cont’d) • During incubation. areas of no growth form a zone of inhibition • Zones are measured to determine whether the organism is susceptible.

test/ Gradient Diffusion Method • “MIC on a stick” • Plastic strips impregnated with antimicrobial on one side • MIC scale on the other side • Read MIC where zone of inhibition intersects E strip scale Dr.E.Sadaf Konain Ansari .

turbi-dimetric. or fluoro-metric methods – Types • BD Phoenix • Microscan Walkaway • TREK Sensititre • Vitek 1 and 2 Dr.Automated Antimicrobial Susceptibility Test Methods – Detect growth in micro volumes of broth with various dilutions of antimicrobials – Detection via photometric.Sadaf Konain Ansari .

Automated Antimicrobial Susceptibility Test Methods • Advantages – – – – Increased reproducibility Decreased labor costs Rapid results Software • Detects multi-drug resistances • ESBLs • Correlates bacterial ID with sensitivity • Disadvantages – Cost Dr.Sadaf Konain Ansari .

Sadaf Konain Ansari . aureus ATCC* 25923 Dr. or manufacturer • Reference strains of QC material – American Type Culture Collection(ATCC) • E. CLSI.Quality Control in Susceptibility Testing • Reflects types of patient isolates & range of susceptibility • Frequency of quality control depends on method. coli ATCC* 25922 • S.

Sadaf Konain Ansari .The Superbugs (important to remember) • Organisms resistant to previously effective drugs • MRSA – methicillin-resistant Staphylococcus aureus – mecA gene codes for a PBP that does not bind beta-lactam antibiotics – Resistant to oxacillin • Vancomycin – VRE –Enterococcus species – VISA/VRSA.Staphylococcus aureus Dr.

aztreonam – Examples: E. IMP). carbapenems.Sadaf Konain Ansari . and aztreonam • Cephalosporinases – AmpC enzyme – inducible – “SPACE” organisms Dr. cephalosporins. coli.The Superbugs: The BetaLactamases • Gram negative rods that have genes on chromosomes that code for enzymes against certain antimicrobials • ESBLs-extended spectrum beta lactamase – Resistant to extended spectrum cephalosporins. penicillins.Class A – Class B (NDM.metallo beta lactamases – Resistant to penicillins. VIM. Klebsiella • Carbapenemases (CRE) – Klebsiella pneumoniae.KPC.

Controlling the Superbugs • Lab’s Role – Recognize and report isolates recovered from clinical specimens – Methods for identification include automated systems and screening agars Dr.Sadaf Konain Ansari .

and proper use of hand hygiene  Minimization of invasive devices (catheters.)  Proper administration of antimicrobial agents where therapy is selected for susceptible organisms for the proper duration Dr. contact precautions.Controlling the Superbugs  Role of Health Care Workers/Facilities  Hand hygiene with the use of alcohol-based hand rubs or soap and water after patient care  Contact precautions for patients identified as colonized or infected with a superbug  Healthcare personnel education about the methods of transmission.Sadaf Konain Ansari . etc.

Sadaf Konain Ansari .Continue Dr.

Lehman. R. T. C. and what is being done.Sadaf Konain Ansari . (2011).gov/std/gonorrhea/lab/diskdiff. MO: Saunders.who. M. & Manuselis.. 45(5). Textbook of Diagnostic Microbiology (4th ed.cdc..biomerieux-diagnostics. MLO. K. Maryland Heights. A. W.int/drugresistance/Antimicrobial_Detection/en /index.. NJ: Pearson Education. R.com/servlet/srt/bio/clin ical-diagnostics/dynPage?doc=CNL_CLN_PRD_G_PRD_CLN_22 • http://www.). 26-30. P.References • http://www. G. Carbapenem-resistant Enterobacteriaceae: what has happened. D. Dr.html • Kiser. • Murray. C. C. (2011).. May). (2013. Clinical Laboratory Microbiology: A Practical Approach . Payne.htm • http://www. • Mahon. & Taff. Upper Saddle River.

Exercise Questions Dr.Sadaf Konain Ansari .

because they effectively escape the effects of antibacterial drugs  Dr.Sadaf Konain Ansari .What are ESKAPE ESKAPEPathogens of Highest Concern The most serious. lifethreatening infections are caused by a group of drugresistant bacteria that the Infectious Diseases Society of America (IDSA) has labeled the "ESKAPE" pathogens.

Common Questions: What stand for MIS. and MBC?  Minimum inhibitory concentration(MIC)  Lowest concentration of an antimicrobial agent that visibly inhibits the growth of the organism. Dr.  Minimum bactericidal concentration (MBC)  Lowest concentration of the antimicrobial agent that results in the death of the organism.Sadaf Konain Ansari .

of an antimicrobial agent  Intermediate “I”  Interpretive category that represents an organism that may require a higher dose of antibiotic for a longer period of time to be inhibited  Resistant “R”  Interpretive category that indicates an organism is not inhibited by the recommended dose. at the infection site. at the infection site. of an antimicrobial agent. Dr.Common Questions: What stands for S. I and R?  Susceptible ”S”  Interpretive category that indicates an organism is inhibited by the recommended dose.Sadaf Konain Ansari .

THANK YOU Email: Sdf_ansari@yahoo.com .