This is appt presentation done by me and my colleagues zakaria Abul-Nasser and Sara Hassan ( agroup of medical undergarduates , school of Medicine, Ain-shams university , Cairo , Egypt ) ...
This work was presented at the end of our Ophthalmolgy clinical round ..
I Hope every one to get the best out of the presentaion ..Any commentaries are even more appreciated :)
Branched Retinal Vein Occlusion (BRVO) for undergraduate MBBS Students.
Covers the basics of Aetiology, pathophysiology, clinical features, types, associated conditions and management of BRVO.
Also encompasses salient points for PGMEE
This is appt presentation done by me and my colleagues zakaria Abul-Nasser and Sara Hassan ( agroup of medical undergarduates , school of Medicine, Ain-shams university , Cairo , Egypt ) ...
This work was presented at the end of our Ophthalmolgy clinical round ..
I Hope every one to get the best out of the presentaion ..Any commentaries are even more appreciated :)
Branched Retinal Vein Occlusion (BRVO) for undergraduate MBBS Students.
Covers the basics of Aetiology, pathophysiology, clinical features, types, associated conditions and management of BRVO.
Also encompasses salient points for PGMEE
Systemic Diseases and the Eye
Various systemic diseases affect the eye and it's functioning. Here we present those common systemic diseases that are responsible to cause effects in the eye.
What are the diseases that affect eye?
Eye is affected by the following diseases:
Systemic Hypertension (Increased blood pressure of the body)
Diabetes Melitus (Increased blood sugar level)
Systemic Lupus Erythromatosus (SLE)
AIDS and other Venereal Diseases like Syphilis
Sickle Cell Anemia,
Eales Disease and many more.
Look at the slides.
Ocular motility disorders: the Approach
Supra- vs infra- nuclear disorders and its related basic science
Other: synkinesis/aberrant regeneration, nystagmus
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
26. Pathognomonic (nearly)
• JIA: chronic anterior uveitis in paeds without
any symptoms Cx band keratopathy,
cataract, or macular edema
• Behçet disease: transitory posterior segment
inflammation
27. Indicators of severe inflammation
•Impairment of visual function
•bilateral disease
•vitreous haze
•macular or optic nerve disease
•retinal vascular inflammation
•macular edema
•exudative detachment
•ocular structural complications that threaten
visual function
33. Uveitis- Ix
• No need if:
– AU 1st episode/UL/non granulomatous/mild-mod without hypopyon
– k/c/o systemic dz/ocular dz for uveitis
Systemic VS Ocular
• Ocular:
– OCT macula, Bscan, FAF/FFA/ICG
– Aq/Vitreous tap: gram stain/C&S & viral/TB/fungal PCR/C&S
– Biopsy: vitreous/conj/iris
• Systemic basic panel:
– FBC, ESR, Mantoux, CXR, VDRL
• Other Inflam Ix:
– Sarcoid panel: LDH/Ca/ACE/lysozyme/CT thorax
– CTD panel: CRP, RF/dsDNA/ANA (esp JIA)/ANCA (esp Wegener +
scleritis/PUK/sinusitis)
– Arthritis: sacroiliac/spine XR, HLA B27
– MRI brain: MS
– HLA: B5/51 (Behcet), A29 (Birdshot)
• Other Ifx Ix:
– Lyme/brucellosis/leptospirosis/toxo serology
– QuantiFERON (IF-gamma release assay)
– HIV
– Prepare for steroid: UFEME/LFT
34. Syphilis Uveitis
• syphilis testing for all uveitis patients, as
syphilis can present as any form of uveitis, and
systemic infection is often undiagnosed
• treating with steroid in the presence of
untreated occult syphilis infection can be
disastrous for patient outcomes
35. Ocular fluid PCR
• HSV1&2/VZV/CMV- Aq=V
• Toxoplasmosis- Aq<V, Aq > if large
lesion/immunoC
• Panbacterial- genetic subunit 16s
• Panfungal- genetic subunit (5.8S/18S/28S)
• Genomic test for primary intraocular
lymphoma
• Goldmann-Witmer (GW) coefficient >
better than PCR for viral & toxoplasmosis
36. FFA in uveitis
• macular edema
• macular ischaemia
• retinal vasculitis
• secondary choroidal or retinal neoV
• areas of optic nerve, retinal, and choroidal
inflammation
• retinochoroidopathies, or white dot
syndromes, have characteristic appearances
42. HLA- principle
• HLA = cell surface molecule (encoded by MHC
gene in chr 6)
• Number= polymorphic form e.g. B-27
• Only support Dx
• Variation with race
• Transplant match (not necessary in cornea)
• WCC
46. Uveitis & geography
• birdshot chorioretinopathy in western
Europe,
• Behçet disease in Turkey and China
• tuberculous uveitis in India
• Histoplasmosis in Ohio/Mississippi valley
• Onchocerciasis in Africa/centra-south
America
47. SEX & UVEITIS
• Seronegative spondyloarthrpathies >M
–women respond to injury or infection with a dominant Th2 immune
response (leading to increased antibody production), whereas men
respond with a stronger Th1 response.
• Autoimmune dz >F
–Estrogen increases the response, whereas androgens suppress.
–Activity depends hormonal stage (pregnancy/menopause)
–Estrogen's effect on autoimmunity may be dose dependent with
lower levels being immune-stimulatory and higher levels immune-
inhibitory.
–Pregnancy with Increased levels of estrogen and progesterone in
pregnancy results in the suppression of Th1 responses and the
upregulation of Th2 responses.
•reduced Th1-associated autoimmune conditions like RA
•exacerbates Th2-associated autoimmune conditions like SLE.
48. Autoimmune
• In general, autoimmune diseases are
mediated by Th1, Th2, and Th17 cells.
• Th1- cell-mediated immunity, with interferon
(IFN)-[gamma] → tissue damage
• Th2- humoral-mediated immunity →
hypersensitivity through IL-4-mediated B-cell
recruitment.
• The role of Th17 cells and their production of
IL-17 ?unsure
49. Spondyloarthropathies
• = sero-ve (RF -ve) or HLA B-27 (80% no sx)
• General: young M >F
– AU: 2nd most common cause (20%), >severe than idiopathic, IU/PU 17%
– ankylosing spondylitis
• 90% H+/AU 25%/>white/sacroiliac & spine
(XR/ankylosis/bamboo)/heart block
–reactive arthritis (Reiter syndrome)
•75% H+/AU 20%/Urethritis-Conjunctivitis-Arthritis/preceded by
ifx/AGE, skin (keratoderma blenorrhagicum- palm/sole brown
abscess)/mouth ulcer
– psoriatic arthritis
•20% of psoriasis/AU 20% (>BL/chronic)/small jt +- dry eye/keratitis
– spondyloarthropathy with IBD (UC/Crohn)- AU (>BL/chronic) +-
PUK/scleritis
– undifferentiated spondyloarthropathy
• IX: RF -ve/XR spine & sacroiliac/HLA B-27
• Mx: AU Mx + systemic steroid/NSAIDS/MTX/AZT, glaucoma watch out
55. JRA/JIA
General h JIA = arthritis of at least 6wk without identifiable cause (<16yo)
h Onset peak 2yo (<16yo), F: M (5:1)
h Usually chronic, most common uveitis in paeds (50%)
h Uveitis after arthritis (95%, 90% of it within 4yr) > before (5%) arthritis
Patho - Non granulomatous
- Genetic and initiated by environmental factor +- infectious agents
Clinical 5 grp: polyA +- RF, pauciA early-late (pauci=oligo= 4or less), systemic
- CAU & AAU
- CAU> no pain/redness + non granulomatous
- Risk of AU: if +ANA/F/pauci-oligo/RF –ve, onset <6yo/within 4 yr of onset for
frequency of eye examination 3mth-12mthly
- F> chronic/Cx/need screen VS M >acute
- Cx: band K 40%, cataract 40%, glaucoma, PS/CMO/ERM, ciliary membrane +-
amblyopia
Mx h Ix: +ANA (>AU), -RF (>AU in polyA RF-ve)
h Screen JIA no uveitis: depends on risk, 3-12mth,
h Monitor JIA +uveitis: 3m if stable, recent change of Rx gutt 1m vs systemic 2m
h Rx: AU topical 1st! Taper+monitor till 3mth if >1drops OD KIV systemic.
h Rx > MTX (1st line) Adalimumab/Humira and infliximab
Remark Taper: topical first 2yr stable then oral IMT (oral steroid is always bringing only)
56.
57. • Recommendations for the screening,
monitoring, and treatment of JIA-associated
CAU and AAU
58. Pars Planitis
General h Young/teen
Patho h Idioppathic
h a/w MS
h DDX toxocariasis (severe IU)
Clinical h IU/snowball/snowbank
h Cx: band K, CMO
Mx h Local steroid (periocular)
Remark
59. Behcet
General h systemic occlusive vasculitis
h > Asian/>M/30s
h BL 80%
Patho h Unknown/Genetic (HLA B51/B5)/autoimmune/ifx
h artery & vein occlusion with Tcell/neutrophil infiltration (non granulomatous)
h Rapid symptoms resolution 1-2wk bu t frequent relapse
h Non granulomatous
Clinical h Japan diagnostic system: 4major = complete (oral/skin/genital ulcer + uveitis),
incompete/suspect/possible
h ISG: oral ulcer (=/>3x/yr) + any 2/4 (genital/skin ulcer/uveitis/pathergy +ve)
h ICBD 2011 9=/>3pt): ocular 2pt, genital 2pt, oral/skin/pathergy/vascular 1pt
h Eye (70%): PanU + retinal vasculitis/necrotizing/ischemia/atrophy
- Hypopyon: Shifting, non granulomatous AU, cold, angle +- pigment pellets
- BRAO/BRVO, glaucoma, cataract, OD atrophy
h Systemic: CNS IIH/thrombosis, GI, CVS, arthritis
Mx h ESR/CRP/CXR/MRI brain & FFA perivascular staining + fern-like leakage
(capillaries >3quad)
h steroid → IMT (AZT → CSA/infliximab/MTX)
60. Sarcoidosis
General h Multisystem non caseating granulomatous dz
h 20-50 vs early onset (<5), ethnic (>european/african), F=M
h 90% lung/50% ocular/10% of uveitic cases
Patho h Unknown/Genetic (I/II HLA DRB1)/Infection (ACCESS)
h Granuloma/Langerhans/inclusion body (Schaumann/Asteroid)
Clinical h Systemic vs ocular, definite/presumed/probable/possible
h Ocular: acute/chronic/pan-uveitis (granulomatous), tent PAS, TM nodule
OD/choroid/retina granuloma, vasculitis/candle wax dripping (irreg granuloma
along veins)
h Orbital: granuloma/infiltration (conj/eyelid/lacrimal gland/7CNP)
h Acute: Lofgren (EN), Heerfordlt syndrome (parotitis)
h variant Mikulicz syndrome (BL sym lacrimal +- salivary gland lymphocytic
infiltration)
Mx h Peripheral anergy test
h CXR (Type I-III)/CT → Ca/ACE/lysozyme/liver enzyme → HPE biospy
h Steroid/IMT/cycloplegic
61. International Workshop on Ocular Sarcoidosis (IWOS)
• 7signs:
– (1) mutton-fat keratic precipitates (KPs)/small granulomatous KPs and/or iris nodules
(Koeppe/Busacca),
– (2) trabecular meshwork (TM) nodules and/or tent-shaped peripheral anterior synechiae (PAS),
– (3) vitreous opacities displaying snowballs/strings of pearls,
– (4) multiple chorioretinal peripheral lesions (active and/or atrophic),
– (5) nodular and/or segmental peri-phlebitis (± candlewax drippings) and/or retinal macroaneurism in
an inflamed eye,
– 6) optic disc nodule(s)/granuloma(s) and/or solitary choroidal nodule, and
– (7) bilaterality
• 5labs Ix:
– (1) negative tuberculin skin test in a BCG-vaccinated patient or in a patient having had a positive
tuberculin skin test previously,
– (2) elevated serum angiotensin converting enzyme (ACE) levels and/or elevated serum lysozyme,
– (3) chest x-ray revealing bilateral hilar lymphadenopathy (BHL),
– (4) abnormal liver enzyme tests, and
– (5) chest CT scan in patients with a negative chest x-ray result.
• Four levels of certainty for the diagnosis of ocular sarcoidosis (diagnostic criteria) were
recommended in patients in whom other possible causes of uveitis had been excluded:
– (1) biopsy-supported diagnosis with a compatible uveitis was labeled as definite ocular sarcoidosis;
– (2) if biopsy was not done but chest x-ray was positive showing BHL associated with a compatible
uveitis, the condition was labeled as presumed ocular sarcoidosis;
– (3) if biopsy was not done and the chest x-ray did not show BHL but there were 3 of the above
intraocular signs and 2 positive laboratory tests, the condition was labeled as probable ocular
sarcoidosis; and
– (4) if lung biopsy was done and the result was negative but at least 4 of the above signs and 2
positive laboratory investigations were present, the condition was labeled as possible ocular
sarcoidosis
62. SO
General h BL diffuse granulomatous panU with prior ocular trauma/op
h rare/2% of uveitic cases
Patho h Unknown/Genetic (HLA DR/DQ 4/W53/B)
h exposed uvea → conj lymphatic → spleen (autoAb) & LN (cell mediated ) →
autoAb vs uveatogenic tissue (retinal/choroid)
Clinical h onset: >5/7, 80% <3mth>, 90% <1yr>, the rest anytime
h BL PanU: >PU/choroid granuloma, Dalen Fuchs (btw RPE-bruch/mid
equatorial/epithelioid + pigment) + AU (granulomatous) + Cx sunset glow
h +- systemic features (like VKH)
h NO retinal/chorio-capillary involvement
h + ext to sclera/OD/macula/vessels
h FFA: Dalen Fuch (hypo then hyper), leak/pool (SRF/RPE/chorioV >VKH), ICG
(hypo choroidal lesion)
Mx h Enucleation within 2wk injury
h Steroid (slow taper 6/12) + IMT
63. VKH & SO- The Similarity
• Bilateral, young-old age
• Diffuse granulomatous inflammation
• Non necrotizing
• Autoimmune
• Genetic predisposition (HLA DR4/53/DQ4)
• Systemic features (CNS/Ear/Skin)- VKH > SO
• CNS: menigismus, CSF pleocytosis
• Ear: tinnitus/dysarcusis
• Derm: poliosis/vitiligo/alopecia + Sugiura sign (perilimbal vitiligo)
• S&Sx of granulomatous PanU
• Dallen Fuchs nodules
• Choroiditis
• Exudative RD & subretinal fluid – VKH > SO
• Sunset glow/PPA
• Treatment with immunosuppressor/steroid
64. VKH VS SO
VKH SO
Pathogenesis
Against melanocyte Uveitogenic vs antibody
Genetic predisposition > autoimmune Autoimmune > genetic predisposition
Risk factors
Associated with systemic dz Assocaiated with eye trauma/surgery
Asian/Black/Dark pigmented No preference
Pathological changes
4 stages: prodrome/acute
uveitic/convalescent/chronic recurrent
No stages
Choriocapillaries involvement
(FFA starry night/fern-like cap leak)
uncommon
67. WDS- General
• Choroidal inflam involved choriocap (hypoperfusion)/outer retina/RPE
• Idiopathic +- autoimmune/ifx
• DDx: TB/syphilis/POHS/ifx, sarcoidosis/VKH/SO/CTD, choroidal mets/lymphoma
• EpiD:
– Young female myopic: MEWDS/MFC-PIC-MCP/AZOOR/AMN, birdshot (older)
– M=F & young to middle-age: APMPPE/serpiginous
• SympT: acute BOV/scotoma
– UL: MEWDS
– BL: APMPPE/Serpiginous
– UL BL: birdshot/AZOOR
– Viral prodrome: APMPPE/MEWDS/AZOOR
– Self limited: APMPPE/MEWDS, PIC/AMN/AIM/ARPE
– Progress/recur: Serpiginous/Birdshot/MCP/AZOOR (Cx: CNV/CMO/atrophy/ERM)
• Signs: choroiditis + min AU/vitritis (no systemic inflam/ifx)
– Placoid/serpiginous (size 1-2DD): APMPPE (post pole)/serpiginous (periOD)/Birdshot (smaller
fleck/periOD)
– Dots : MEWDS (wheath cluster), Birdshot (periOD), MFC (curvilinear), AZOOR (zonal)
• Ix- OCT: elevation@outer retina/disruption of outer hyperR band/IS-OS+-CMO/CNV
• Ix- FFA: early hypo (block) late hyper (leak/stain) +- window defect (atrophy)
• Ix: ICG: persistent hypo (lesion > than clinically)
• Ix: FAF: hyper if sick, hypo if dead RPE
• Ix: EOG abn (RPE), ERG initially normal a-wave abn
• Mx: observe steroid
68. APMPPE
General h M=F + young to middle-aged
h +-HLA B7/DR2
SSx h Acute BL (pre-URTI) resolved <wks> +-persistent/relentless
h Multifocal/cream colour placoid size 1-2DD @post pole
Mx h Observe (good recovery) > steroid
Remark ● a/w cerebral vascullitis, headache, hearing loss, tinnitus
Serpiginous
General h M=F + young to middle-aged
h HLA B7
SSx - Acute BL recurrent BOV/scotoma persistent
- PeriOD centripedal serpiginous (pseudopodial/map-like) scar +
new
Mx Steroid/IMT/CNV Rx
Remark Guarded prognosis
69. Birdshot
General h White Caucasian + >F + middle-aged (30-70)
h HLA A29 (95%)- normal white population 7%
Clinical h Acute UL to BL progressive/relapsing x years persistent BOV/scotoma
h Criteria x 3 (BL symmetrical + Birdshot flecks/mild vitritis/CMO + HLA A29)
h Choroiditis- periOD >inf/post pole (oval cream colour/size ¼- 1 ½ DD), no
pigment
h Atrophic scar- punched out clear margin
h Cx: vasculitis/OD edema-atrophy/CNV/CMO/RP-like (with minimal pigment)
Mx - Steroid +- 2nd line
Remark ERG negative pattern (normal a but reduce b)
Guarded if untreated
70. MEWDS
General h Young +F+myopia + UNILATERAL!!
SSx - Acute UL (pre-URTI) self limiting
- White dots (wheath cluster)/transient flecks @ post pole
Mx - Observe > steroid
MFC/MCP/PIC
General h Young+F+myopia
Clinical h Acute BL PIC self limit VS MCP progress/Cx
h Dots- discrete cluster/100-300um @ post pole/periOD Schlaegel lines
(curvilinear pattern)
h Late → punched out/atrophic scar, CNV (25-50%), CMO (rare)
Mx -steroid > observe/Rx Cx (CNV/CMO)
AZOOR
General h Young+F+myopia
Clinical h Acute UL to BL progress persistent BOV/scotoma
h Dots- OD/post pole zonal lesion Late → atrophy/RP-like
Mx -steroid > observe
71. Others WDS
Young F & UL > BL & self limiting + pre URTI
1. Acute macular neuroretinopathy
– brown-red/wedge-tear drop-pedal shape
lesion/tips point center
2. Acute idiopathic maculopathy
– M=F & sudden severe central LOV
– ERD/RPE disturbance/Bull’s eye
3. Acute idiopathic blind spot enlargement
– OD neuritis (RAPD) + blind spot enlarge + pigment
4. Acute RPE epitheliitis (Krill dz)
– hyperP lesions + yellow hypoP halo @post pole (FFA reverse)
80. MUST
• Multicenter Uveitis Steroid Treatment trial
• Up to 7 yr follow up
• Adequate immunosuppression to taper
prednisone to 7.5mg/day or less, together with
IMT VS long-lasting regional corticosteroid
therapy (fluocinolone acetonide implant)
– systemic adverse effects were no greater, except
for a greater use of antibiotics for infections
– superior visual outcomes because chorioretinal
damage @uveitis relapse before re-implant of the
regional therapy saw-tooth decline
81. SITE
• Systemic Immunosuppressive Therapy for Eye
Diseases
• 9250 patients with ocular inflammation with up to
30 years of follow-up
• Risk of cancer for IMT
• TNF inhibitors: increased total and cancer mortality
• Alkylating: non-statistical significant increase risk of
cancer
• Antimetabolites or calcineurin inhibitors: no
significant risk
82. Prednisolone
• Initiation
– 1 mg/kg/day up to a maximum of 60 mg/day
– range 0.5-2mg/kg/day
– >60 mg/day = increased risk of ischemic necrosis of bone
– IVMP 1g x 3d: if need immediate control, followed by oral steroid +-
IMT, avoid rapid IV (<30min) arrhythmia/MI/ifx
• Taper
– After 2 to 4 weeks
– of control/resolve/improve
– Target dose is =/<7.5mg/day
– Still increased risk of CVD
• 5 mg/day x 22yr
• 7.5 mg/day x 15yr
83. Prednisolone
• Flare/Exacerbation
– TRO ifx/non adherence/DDx/rapid taper with rebound
– If tapering resume a higher dosage for another
month or until the disease is quiet taper back to just
above the threshold at which the disease reactivated
– Taper slower/longer if =/<7.5mg OD <3mth still
– IMT if >7.5mg OD >3mth already
• Stop with remission
– hypothalamic–pituitary axis may not return for 6 to 12
months after tapering for chronic cases adrenal crisis
84. Prednisolone- AE/Monitor/Supplement
• Short-term: ifx, BP, DXT
• Long-term: immune, bone, cushing, psychosis
• Eye: IOP, cataract, ifx
• Metabolic: HPT, fluid retention, DM, hyperlipidemia, atherosclerosis
• Cushingoid (moon facies, weight gain, fat redistribution, and increased acne)
• Immune: Infection
• Bone Skin: Osteoporosis, easy bruising, and poor wound healing, delay growth <15yo
• Psy: Anxiety, sleeplessness, mood changes
• Monitor
– BP and blood glucose q3mth
– Bone BMD yearly
– Lipid profile yearly
• Supplement
– 1500mg Ca, 800 IU Vit D daily (esp 1st 6-mth- greatest bone loss)
– If BMD=osteoporosis antiresorptive e.g. calcitonin/alendronate
– H2 blockers for patients taking prednisone is unnecessary ?PPI
85. IMT- IndiC
Therapeutic needs, Uveitis type, Severity
• Steroid-sparing:
– prolonged steroid >3mth & >7.5mg/day
– SE, intolerate
– Poor response
– worsens on high-dose
– no response after 2-4wk
– better but not quiet after 4 wk of high dose
– relapse despite 7.5mg OD
• Initial Rx in:-
– Poor natural history
– OCP with ocular involvement
– Behcet with posterior segment involvement
– SO/VKH, serpiginous choroiditis, Birdshot
– Systemic protection
– necrotizing scleritis & PUK with systemic vasculitis
– Severe advanced inflammatory damage
– Reserved as 2nd line:
– SE & cancer risk
– bladder cancer (cyclophosphamide), leukemia, lymphoma, non melanoma skin
cancer (AZT & CSA for postTx case) and, possibly, overall cancer.
86. IMT- How to choose
• Availability/cost AE vs efficacy
• Antimetabolite
– MMF & AZT- most effective
– AZT vs MMF – least & best tolerable
– MTX- best for paeds, worst for fetus
– MTX- not for hepatitis or alcoholic
• T cell inhibitors
– CSA- less effective vs antimetabolite
– > combination therapy w antimetabolite
– Not for CKD
• Alkylating
– most potent & potentially remission-inducing
– BUT most SE/cancer risk, IV pulse or oral daily
87. IMT- Pre & Starting
• baseline vital organ function (liver/kidney/BM)
• screen for active/latent infectious diseases
• TRO pregnancy & chance
• history of malignancy & testing for TB & HIV
before biologic therapy
• Administration
– bridging with steroid (wk-mth)- high dose if active/relapse,
same dose if stable
– Taper of steroid after 4-8wk
– monitoring blood tests (1wk-2wk-4wk-2mth-3mth)
– DDX inadequate suppression/ifx due to over suppression
– Other systemic features of ifx VS inflam
– Lymphocyte count 0.8-1.2 = adequate
88. IMT- Increase, Combine & Taper
• Step up dose
– Dose escalation: low dose increments every 4-6weeks optimal
dose
– Rapid incrementation: low dose 2wk to assess tolerability
max/optimal dose (esp for MTX & MMF)
• Combination
– Antimetabolite + CSA
– Alkylating usually solo
– Antimetabolite + biologic
• Taper/off IMT/2nd line
– Usually after off the oral prednisolone
– Usually >3yr use & >2yr stable/control for non-alkylating
– Usually >3yr use & >1yr stable/control for alkylating
– Taper slowly with long duration each of step (3-6mth)
90. IMT in Pregnancy
• CI in pregnancy: cyclophosphamide, chlorambucil
and methotrexate.
• Esp MTX (category X)
– even in a male patient who may impregnate someone
– Evan also CI for BF
– use two forms of birth control.
– at least three months after it is stopped.
– But very good for paed uveitis/JIA
– Use topical/regional medication if possible
– Pregnancy = progresterone more = more anti-
inflammatory but post partum flare
91. IMT- Paeds
• MTX
• +- CSA
• Growth
• should not receive live virus vaccine (MMR vaccine, varicella-
zoster virus vaccine, oral polio vaccine, BCG) while on therapy for 3
months after stopping therapy or > 20 mg prednisone daily
• If possible, varicella-zoster vaccine should be given before the
start of therapy.
• systemic viral diseases, they should receive a yearly influenza
vaccine, and if susceptible, varicella-zoster virus immune globulin
upon close exposure to chickenpox.
• If CD4 <200 cells per ml, consider P. carinii prophylaxis.
92.
93. Azathioprine (Imuran)
• Purine (A&G) analogue
• MOA: activated to 6-mercaptopurine (6-MP) by thiopurine
S-methyltransferase (TPMT, enzyme activity = Rx response)
→ false coding → - DNA replication/RNA transcription
• Dose: start 50 mg/day x 1wk → most effective at
2mg/kg/day (aim) 3-4mg/kg/day (unusual)
• IndiC:
– Ocular: Behçet disease (1st)/VKH/SO, IU, necrotizing scleritis,
Wegener
• SE:
– GI (25%), BMS/pancytopenia, hepatotoxic (2%) → FBC/LFT!!
– Use lower dose if +allopurinol
– LFT q12 weeks. When toxicity occurs (> 1.5 times upper
limit of normal), the dose should be decreased by 25 to 50
mg per day, and LFT 2 weeks. If > 5x upper limit
discontinued
94. Methotrexate
• Preferably 1st choice for paeds uveitis & sarcoidosis
• Folic acid analogue
• MOA: - dihydrofolate reductase (DHFR) → - thymidylate/purine
synthesis → - DNA/RNA/AA & adenosine release (anti-inflammation)
• IndiC:
– Systemic CTD esp RA, sarcoidosis
– Ocular esp JIA & paeds uveitis (1st line!), scleritis
– Lymphoma
• Dose
– Weekly dose: 2.5mg-7.5mg weekly, 10mg (Start) → 15mg (aim) 25mg
(max) (need 6wk for effect 6/12 to peak effect)
– + folinic acid/folate 1mg OD (except on day of MTX)
– IVT 400ug for refractory uveitis/uveitic CME
• SE
– GI (10%), BMS, hepatotoxic (15%), teratogenic → FBC/LFT/no pregnant/no
hepatitis/no alcohol, or need to stop >3/12 before pregnant!, double
contraceptive
96. Cyclosporin
• Preferably as add-on after antimetabolite
• Fungal Baeuveria
• MOA: - T cell signal → - transcription of IL/cytokines
• Indication:
– systemic: CTD (RA/SLE), nephrotic syndrome
– ocular: VKC/AKC/rosacea/blepharitis, uveitis/graft vs host,
dry eye, Behcet (2nd)
• Dose
– RA: start 1mg/kg BD (50-100mg/day) → step up q4wk →
max 2mg/kg BD 2.5mg/kg BD (unusual)
– Excrete biliary
• SE: HPT, renal/neuro-toxic, gingival hyperplasia →
BP/RP/LFT/FBC!! +Mg/lipid profile
97. Tacrolimus & Sirolimus
• Fungal Streptomyces
• Tacro= calcineurin inhibitor (-T/-IL)
– Dose: 0.05–0.15 mg/kg/day
– Vs CSA: lower dose/more potent/less SE (still
need FBC/RP)
• Siro= non-calcineurin inhibitor (-T/-AB & B
cell)
98. Cyclophosphamide
• Alkylating agent
• most potent & potentially remission-inducing
• MOA: cross link/alkylate purine (>G) of DNA → cytotoxic/- rapid
proliferating/mitosis cells → - T/B cell
• IndiC:
– Systemic: CTD esp SLE/Wegener/GPA/vasculitis/RPC
– Ocular: Mooren, MMP, Behcet/VKH/SO
• Dose
– Oral OD, or pulse IV monthly (oral > effective than pulse IV)
– Oral 2mg (1-3)/kg/day (peak effect 1yr) --> dose is adjusted to achieve a
white blood count in the 3000 to 4000 cells/ml range when the
patient is not taking prednisone.
– Treatment is continued for 1 year and then tapered to determine if a
remission has been induced
• SE
– cystitis/hematuria, sterility, teratogenic, malignancy risk (leukemia/bladder
CA), BMS/leucopenia, increase IOP
– Monitor: FBC/UFEME & drink >2L H2O
– Opp ifx: +- PCP consider bactrim prophylaxis
99. Chlorambucil
• Alkylating agent
• Dose: 0.1–0.2 mg/kg/day adjust similar to
cyclophosphamide
• “high-dose, short-term”: start at 2 mg/day
escalated weekly until uveitis controlled or bone
marrow suppression treatment is
discontinued; the mean maximum dose with this
approach is 20 mg/day
– Less SE/risk of cancer
• SE: BMS, sterility, teratogenic → FBC!
100. Infliximab (Remicade)
Adalimumab (Humira)
• TNF-alpha inhibitor
• IndiC:
– JIA, AS/spondyloarthropathies/HLA B-27
– idiopathic uveitis/behcet (2nd)/VKH/SO
• Administration
– Infli- IVI 5-8mg/kg @ D1/wk2/wk6 then q8wk
– Adali- subcutaneous 80mg stat 40mg weekly x1 40mg q2wk
• SE
– Malignancy cervical CA (need yearly pap smear)
– Ifx TB reactivation → Mantoux/CXR + for prophylaxis!
FBC/HepB/HepC/HIV screen
– Worsen MS
– New hypersensitivity/autoimmune dx lupus, demyelinating dz, VH
– CCF, thrombosis
– less BMS
108. Pathergy
• Pathergy= immune system is overreacting to a minor injury
• Indications:
– Behçet's disease
– pyoderma gangrenosum
• Methods:
– skin prick test with sterile needle 22-18G → 24-48H
– small red bump or pustule at the site =+ve
– lesion +- resistant to healing (but subsequently healed with
steroid)
• Limitations:
– highly similar phenomenon (Koebner) @ autoimmune
dz/psoriasis/SLE
– sensitivity depends on race- Asian 50%, more in Mediterranean
– Caution may influence Mantoux test!
109. Mantoux
• intradermal injection of 2TU/0.1ml of PPD - Statens Serum
Institute (SSI) tuberculin RT23 → 48-72H
• Limitation:
– does not measure immunity to TB but the degree of
hypersensitivity to tuberculin
– no correlation between the size of induration and
likelihood of active TB but correlated with the future risk
of developing TB disease.
• Mantoux conversion
– second of two Mantoux tests increases by =/> 10mm
(newly obtained infection within that period) – DDX
boosting effect
111. Mantoux- Limitation
• False-Positive
– nontuberculosis mycobacteria (NTM)
– Previous BCG vaccination (aft 2mth)
• False-Negative
– anergy
• very young age (less than 6 months old)/very old
• Recent live-virus vaccination/viral illnesses (e.g., measles and smallpox/chickenpox
– very recent TB infection (within 8-10 weeks of exposure)
– very old TB infection (many years) → A repeat test /2-steps test/boosting
effect (1wk after) can result in a larger response (boosting can occur up to
2years)
*Incorrect method of administration/interpretation/Ag
112. Anergy
• Anergy= inability to mount a delayed-type hypersensitivity (DTH)
response to a battery of common skin test antigens → =
suppression of cell-mediated immunity.
• Methods
– Mantoux-method tests with 3x Ag (PPD + mumps/Candida/tetanus, all
0.1ml), used together and with cut-off diameters of 5 mm of induration
• Indications
– Immunosuppressed persons (HIV with PPD skin test reaction is
unknown/-ve )
• Factors limiting
– less standardization and reproducibility
– low risk for TB associated with a diagnosis of anergy
– lack of apparent benefit of preventive therapy for groups of anergic
HIV-infected persons.
114. Kveim Test
• Nickerson-Kveim or Kveim-Siltzbach test
• skin test for sarcoidosis
• Spleen tissue from a patient with known
sarcoidosis is injected into the skin of a
patient suspected to have the disease.
– +ve if non caseating granulomas are found (4–6
weeks later)
– False –ve: glucocorticoids treatment
115.
116. Classical uveitis language
• Classical template for history taking
• Classical template for ocular examination
• Classical battery of tests/investigation
• Diagnosis with classical Terminology &
Classification
• Classical management plan
• Classical for Part 2 exam goers in Malaysia…
there are not basic
• Basic = relevant & targeted history, examination
& investigation individualized
120. Coming
• OCT-A characteristics of active and inactive
chorioretinal lesions
• EDI-OCT structural alterations in several
uveitic diseases- VKH SO birdshot
• OCT based objective grading of intraocular
cells/inflammation.