This document discusses various topics in ophthalmic pathology and pharmacology. It covers: 1. The definitions and main branches of pharmacology, including pharmacokinetics and pharmacodynamics. 2. Different routes of drug delivery to the eye, including topical, local injections, and systemic administration. 3. Classes of anti-inflammatory drugs used to treat ocular inflammation, such as glucocorticoids, NSAIDs, mast cell stabilizers, and antihistamines. 4. Specific drugs used for various ocular conditions and their adverse effects. 5. Processes of wound healing, tissue fixation and processing, orientation and dissection of eye specimens, and staining for

1. & PATHOLOGY
Dr. Vinit Kumar

2. • Pharmacology :
• Branch of medicine concerned with the uses, effects & mode of action of
drugs .
• A drug can be defined as a chemical substance used in the
treatment, cure, prevention, or diagnosis of disease or used to
enhance physical or mental well-being.
• The2 main branches of pharmacology are pharmacokinetics
and pharmacodynamics.
Introduction

3. • Pharmacokinetics
• concerns the cycle of a drug through
the body, including the absorption,
distribution, metabolism, and
excretion of that drug.
• Pharmacodynamics
• Refers to the biological activity and
clinical effects of adrug.
• It is the drug action after
pharmacokinetics has distributed the
active agent to the therapeutic site.

4. Pharmacokinetics
(TheRoute of DrugDelivery)
Topical Local systemic

5. • Eyedrops
• Most ocular medications are administered topically aseyedrops. This
route of administration maximizes the anterior segment
concentrations while minimizing systemictoxicity.
Topical

6. • The factors determining the amount of medication that can penetrate the cornea are
1. concentration and solubility in thedelivery vehicle,
2. viscosity,
3. lipid solubility,
4. the drug’s pH, ionic and stericform,
5. molecular size,
6. chemical structure andconfiguration,
7. vehicle,
8. surfactants,
9. reflex tearing
10. the binding of the active medication to proteins in tears and tissue.

7. Local Administration
• Periocular injections
Injection of medication beneath the conjunctiva or the Tenon capsule . Subconjunctival,
sub-Tenon, and retrobulbar injections all allow medications to reach therapeutic levels behind the
lens–iris diaphragm.
for example, posterior sub-Tenon injections of steroids for cystoid macular edema (CME) or
subconjunctival injection of MMC / 5-fluorouracil aftertrabeculectomy.
• Intraocular medications
There are 2 types of intraocular injections: intracameral injections into the anterior chamber
intravitreal injections into the vitreouscavity.

8. Systemic Administration
• Sustained-release oral preparations
• Intravenous injections
Mannitol
sodium fluorescein for FFA and indocyanine green , are used for retinal
angiography.
• Intramuscular injections
an useof botulinum toxin in Facial Palsy .

9. Anti-inflammatory Drugs

10. • Ocular inammation canbe treated with medicationsadministered
I. Topically
II. local injection
III. ocular implantation
IV. systemically.
Thesedrugs may be classiedas
1. Glucocorticoids.
2. Nonsteroidal anti- inammatorydrugs
3. Mast-cell stabilizers
4. Antihistamines
5. Antifibrotics.

11. Glucocorticoids
• topically to prevent or suppress ocular inflammation in trauma and uveitis, as well as
after most ocular surgicalprocedures
• Subconjunctival and retrobulbar injections of steroids are used to treat more severe cases
of ocularinammation.
• Intravenous methylprednisolone is an option in treatment of optic neuritis .

12. Adverse effects
• Complications in the eyeinclude
1. glaucoma
2. posterior subcapsularcataracts
3. exacerbation of bacterial and viral(especially
herpetic) infections through suppression of
protective immune mechanisms
4. fungal infection
5. ptosis
6. mydriasis
7. scleral melting
8. eyelid skin atrophy
9. pseudohypopyon from intraocular injection
10. central serous retinopathy
• In the body, oral dosescancause
1. suppression of the pituitary–adrenalaxis
2. gluconeogenesisresulting in hyperglycemia.
3. muscle wasting
4. osteoporosis
5. redistribution of fat from the periphery to
the trunk
6. central nervous systemeffects, suchas
a) euphoria
b) insomnia
7. aseptic necrosis of the hip
8. peptic ulcer
9. diabetes mellitus
10. occasionally, psychosis

16. Specific drugs
• Cyclooxygenase inhibitors are less effective than steroids in the treatment of scleritis and uveitis.
• NSAIDs such as indomethacin can be used in patients with cataract surgery has been reported to reduce the
incidence of CME, &increasevision
Ketorolac tromethamine (0.4%,0.45%,0.5%,and generic 0.5%)
• hasbeen approved by the FDAfor the treatment ofpostoperative inflammation and allergic conjunctivitis.
• use 4 times per day.
• Themost common adverse effects are stinging and burning on instillation(40%).

17. Nepafenac, 0.1%,
• was approved in 2005 for 3-times-daily dosing for pain and inflammation 1 day before and 2
weeks after cataract surgery.
Bromfenac sodium, 0.09%,
• Usedafter cataract surgery for decrease in pain
and inflammation.
• All NSAIDsare associated with corneal complications,including
i. melting
ii. corneal perforation

20. • Somedrugs, including olopatadine, ketotifen, nedocromil, epinastine, azelastine,and
have amast-cell-stabilizing effect aswell asH1-antagonism.
• Thesedrugs provide immediate relief against released histamine and prevent thefuture
degranulation of mastcells.
• Olopatadine HCl, 0.1%,
• olopatadine, 0.2%. Adverse reactions of ocular burning, stinging, dry eye, foreign- body
sensation, hyperemia, keratitis, eyelid edema, pruritus, asthenia, cold syndrome,
pharyngitis, rhinitis, sinusitis, and taste perversion were all reported at an incidence of
lessthan 5%.
• ketotifen fumarate, 0.025%,
• Nedocromil sodium, 2%,Recalcitrant casesof severe allergic, vernal, and atopic
conjunctivitis may require the short-term useof stronger topical steroids .

21. ANTI GLAUCOMA MEDICATION
• Alpha adrenergic agonist
• Non selective B- blockers
• CA- Inhibitor
• Diuretics

22. Ocular pathology

23. Defination
• Pathology : is study of or branch of medicine which deals with cause & effects of
disease or injury
• In ophthalmology pathology is useful in diagnosis of ocular tumour, uveitis
(anterior/intermediate/posterior/panuveitis), sympathetic ophthalmia, Retinoblastoma,
choroidal melanoma, glaucoma, neuroophthalmology, retina & cornea
• In cornea it deals in corneal degeneration, corneal ulcer, dystrophy & healing of corneal
ulcer or corneal epithelial healing etc.

24. Wound Repair
• Thepurpose of wound healing is to restore the anatomical and
functional integrity of an organ or tissue asquickly and perfectlyas
possible.
• Theprocess may take many months.
• Theend result is typically ascar.

25. Sequenceof general wound healing with an epithelialsurface
• 1, Thewound is created. Blood clots in the vessels;neutrophils migrate to the wound; the
wounded edgesbegin to disintegrate.
• 2, Thewound edgesare reapposed & epithelium is lost over the wound but starts to migrate.
The stromal/dermal fibroblasts enlarge and become activated.Theblood vesselshelps to
produce new tissue.
• 3, Theepithelium sealsthe surface. Fibroblasts and blood vesselsenter the wound andlay
down new collagen. Much of thedebris is removed by macrophages.
• 4,Asthe scarmatures, the fibroblasts subside. Newly formed blood vesselscanalize.New
collagen strengthens the wound, which contracts. the striated muscle cells in the
subcutaneous tissue do not regenerate and are replaced by ascar.

28. Fixatives for Tissue Preservation
• Themost commonly used fixative is 10%neutral-buffered formalin.
• Formalin is a 40%solution of formaldehyde that stabilizes proteins, lipids, and carbohydrates and
prevents enzymatic destruction of the tissue(autolysis).
• In specific instances, other fixatives may be preferred, suchas
i. glutaraldehyde for electron microscopy,
ii. ethyl alcohol for cytologicpreparations,
• Formalin diffuses rather quickly through tissue. Because most of the functional tissue of the eye
is located within 2–3 mm of the surface, it is not necessary or desirable to open the eye.

30. Orientation
• Globes may be oriented according to the location of the extraocular muscles
and of the long posterior ciliary arteries and nerves, which are located in the
horizontal meridian.
• Locating the insertion of the inferior oblique muscle is very helpful in
distinguishing between aright and aleft eye.
• Theinferior oblique inserts temporally over the macula, with its fibers
running inferiorly. Oncethe laterality of the eye is determined,accurate
location of ocular lesions ispossible.

32. Gross Dissection
• Prior to grossdissection, eyesare transilluminated with bright light.This
helps to identify intraocular lesions suchastumors, which block the
transilluminated light and cast ashadow
• Theshadow canbe outlined with amarking pencil on the sclera.
• Thisoutline canthen be used to guide the grossdissection of theglobe
sothat the center of the section includes the maximum extent of the
area of interest.

34. • Themajority of eyesare cut sothat thepupil and optic nerve are present in
the samesection, which is called the pupil–optic nerve (PO)section.
• In routine cases,eyeswith no prior surgery or intraocular neoplasm are
typically opened in the horizontal meridian, which includes the macula in the
samesection asthe pupil and optic nerve.
• Globes with asurgical or nonsurgical wound should be opened suchthat the
wound is perpendicular to, and included in, the POsection.
• Globes with intraocular tumors are opened in away (horizontal, vertical, or
oblique) that placesthe center of the tumor, asoutlinedby transillumination,
in the POsection

36. Processing and Staining
• Tissue Processing
• Theinfiltration and embedding process replaces most of the water inthe
tissue with paraffin.
• Theorganic solvents used in this process dissolve lipids and may dissolve
some synthetic materials.
• Routine processing usually dissolves intraocular lenses made of polymethyl
methacrylate (PMMA), acrylic, or silicone. Sutures made of silk, nylon, or
other synthetic materials do not dissolve during routineprocessing.
• Embedding tissue in aparaffin block mechanically stabilizes the tissue,
allowing for cutting very thin sections through the tissue.

37. Tissue Staining and Slide Preparation
• Tissuesections are usually cut at 4–6μm.
• Thecut section is colorless except for areasof indigenous pigmentation,
and various tissue dyes—principally hematoxylin-eosin and periodic
acid–Schiff (PAS)—are used to color the tissue for identification.
• Asmall amount of resin is placed over the stained section andcovered
with athin glasscoverslip to protect and preserveit..

38. Flow cytometry’s advantage & disadvantage
• advantage
1. it actually shows the percentages ofparticular cells in aspecimen.
2. multiple antibodies and cellular sizecanbeanalyzed.
For example, CD4(helper Tcells), CD8(suppressor Tcells), both CD4+and CD8+,or
either CD4+or CD8+may be displayed for agiven lymphocytic inltrate.
• disadvantages
1. its failure to show the location and distribution of these cells in tissue.
2. the possibility of samplingerrors.
Flow cytometric data should therefore be used asan adjunct tomorphologic
hematoxylin-eosin (H&E)staining and immunohistochemistryinterpretation.

39. Molecular Pathology
• Molecular pathology is used to identify tumor-promoting or tumor-inhibiting genes, such
asthe retinoblastoma gene (eg, via comparative genomic hybridization [CGH],
polymerase chain reaction [PCR],or array CGH),and viral DNAor RNAstrands, such as
those seenin herpes viruses and Epstein-Barr virus (eg, via PCRor in situ hybridization
[ISH]).
• Molecular pathology techniques have made it possible not only to recognize the
presence or absenceof astrand of nucleic acid but also tolocalize specic DNAsequences
withinspecic cells (eg, via fluorescence in situ hybridization [FISH]or ISH).
• Twomajor techniques have markedly advanced our knowledge of developmentalbiology
and tumorigenesis:
1. PCR(and its variations)
2. microarray (and itssubtypes).

40. Microarray
• Scientists and clinicians usemicroarrays to survey the expression of
thousands of genesin asingle assay,the output of which is called agene
expression profile.
• Microarray technology canhelp these scientists andclinicians
1. try to understand fundamental aspects of growth and development,
2. toexplore the molecular mechanisms underlying normal and dysfunctional biological
processes,
3. to elucidate the genetic causesofmany human diseases.

41. Clinical use of PCR and microarray
• Routine clinical use of PCRand microarray has been traditionally limited to the
diagnosis of leukemias, lymphomas, soft-tissue neoplasms, and tumors with
nondiagnostic histopathology results.

42. Diagnostic Electron Microscopy
• Diagnostic electron microscopy (DEM) is primarily used to indicate the cell of
origin of a tumor of questionable differentiation, rather than to distinguish
between benign and malignant processes.

43. Fine-Needle Aspiration Biopsy
• Intraocular fine-needle aspiration biopsy (FNAB) may be useful in distinguishing between primary uveal
tumors and metastases.
• Intraocular FNABhasalso been utilized in the diagnosis of primary intraocular lymphoma.
• The procedure is performed under direct visualization through a dilated pupil, transvitreally or
transclerally.
• FNABalone may reliably predict the prognosis of auveal melanoma.
• Some orbital surgeons have used FNABwhen diagnosing orbital lesions, especially presumed metastases
to theorbit
and optic nerve tumors.
Special Techniques

44. DIFFERENT PATHOLOGICAL METHODS USED IN
DIAGNOSIS OF VARIOUS OCULAR DISEASES
• FROZEN SECTION : usedfor assessingthe marginsin eyelidcarcinomas(eg,basalcell carcinoma,squamouscellcarcinoma,and
sebaceouscarcinoma)

45. Manythanxfor yourattention

46. MANY THANKS FOR YOUR
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