Basic Science: Quick Review

Fran Wu, MD, MPH

Global Ophthalmology Fellow, Emory University
VECD Fogarty Global Health Fellow
31 March 2018
Outline
• Embryology
• Genetics
• Pharmacology
Embryology
 A newborn infant presents
with this finding. What
developmental anomaly
caused this presentation?
A. Incomplete closure of embryonic
fissure
B. Faulty migration of neural crest cells
C. Exuberant proliferation of glial tissue
D. Abnormal retinal differentiation
Answer: A. Incomplete closure of embryonic fissure

• This is a large chorioretinal coloboma

• Coloboma can involve iris, lens,
nerve, retina, and RPE
• Failure of RPE development in RPE
can result in hypoplasia of choroid
and sclera, leading to staphyloma
• Most colobomas are inferonasal
(typical coloboma), but some are
elsewhere (atypical coloboma)
Structure Time Associated abnormalities
Optic pit Day 23
Optic vesicle Day 25 Anophthalmia (very rare)
Lens placode Day 27
Lens vesicle Day 30
Embryonic fissure closes Day 33 • Coloboma. Note: eyelid coloboma is NOT related.
• Microphthalmos with cyst
• Optic pit: atypical, usually temporal, a/w serous RD
Lens vesicle completed Day 33
The following are all remnants of the
hyaloidal vascular system except:
A. Mittendorf dot
B. Corneal leukoma
C. Persistent pupillary membrane
D. Bergmeister papilla
 Answer: B. corneal leukoma
• Corneal leukoma may be seen with Peters anomaly

Mittendorf dot
Persistent pupillary Bergmeister papilla
membrane
Hyaloid artery
• Enters through embryonic fissure
and forms blood supply to primary
vitreous
• Intravitreal portion regresses by
8.5 months
• Intraneural portion becomes
central retinal artery
• Abnormality: Persistent Fetal
Vasculature (PFV) (formerly
Persistent Hyperplastic Primary
Vitreous, or PHPV)
Match the structure with the embryonic
tissue from which it is derived
A. Surface ectoderm
B. Neural ectoderm
C. Mesoderm
D. Neural crest

• Lens
• RPE
• Rectus muscles
• Corneal endothelium
Match the structure with the embryonic
tissue from which it is derived
A. Surface ectoderm
B. Neural ectoderm
C. Mesoderm
D. Neural crest

• Lens – A. Surface ectoderm

• RPE – B. Neural ectoderm
• Rectus muscles – C. Mesoderm
• Corneal endothelium – D. Neural crest
 Lens

• Surface ectoderm forms lens pit  lens vesicle  closes to form sphere
• Basement membrane forms the lens capsule
• Posterior lens epithelial cells elongate and migrate (primary lens fibers),
filling the core and forming the embryonal nucleus at 40 days
• Anterior cells migrate to equator and form secondary lens fibers at 7 weeks
• These fibers encase the embryonal nucleus and form the Y sutures (the meeting of
embryonal and fetal nuclei). The Y is upright anteriorly, inverted posteriorly.
 Embryologic tissue origins
Surface Ectoderm
L ens
E pithelium of conj and skin
V itreous
E pithelium of cornea
L acrimal (nasolacrimal) system
Neural Ectoderm Mesoderm
N erve (optic nerve) M uscles
E pithelium of ciliary body E ndothelium of blood vessels
R etina and RPE S clera (temporal portion)
V itreous O ther (Vitreous)
E pithelium of posterior iris
S phincter and dilator of iris

Neural Crest – everything else

Corneal stroma and endothelium Sclera (except temporal portion)
Iris stroma Sheaths and tendons of EOMs
Trabecular meshwork, Schlemm’s canal Choroid
Ciliary muscle Orbital bones
Genetics
Autosomal Dominant
• One copy of the gene results in disease
• Each pregnancy has a 50% chance of disease
• Males and females are equally affected
• Both mother and father can transmit the gene
• AD diseases
• Most corneal dystrophies except macular, type 3 lattice, gelatinous, and
nystagmus-associated CHED
• Many phacomatoses, including neurofibromatosis, tuberous sclerosis,
and Von Hippel-Lindau disease
Autosomal Recessive
• Two copies of the gene are needed for disease (homozygous)
• If both parents are carriers, each pregnancy has a 25% chance of
disease, 50% chance of being a carrier, and 25%
chance of neither
• Males and females are equally affected
• Both mother and father can transmit gene
• AR diseases
• Stargardt’s disease (think stARgardt’s)
• Leber’s Congenital Amaurosis
• Oculocutaneous albinism
• Microcornea
Mitochondrial inheritance
• Also known as maternal inheritance
• Only egg cells contribute mitochondria to
the developing embryo
• Only mother can transmit disease
• Males and females can be affected
• Mitochondrial inheritance diseases
• Leber’s Hereditary Optic Neuropathy (LHON)
• Chronic Progressive External
Ophthalmoplegia (CPEO)
 X-Linked Dominant
• Only one copy of the gene on the X chromosome is required for
disease
• Disease in males (XY) is usually severe or lethal
• If mother is affected, daughters have 50%
chance of disease
• If father is affected, daughters have 100%
chance of disease, sons 0%
• X-linked dominant diseases
• Aicardi syndrome
• Incontinentia pigmenti
X-Linked Recessive
• Only one copy of the gene is required for disease in males (XY); two copies of
the gene are required for the disease in females (XX)
• If mother is a carrier, male offspring have 50% chance of disease
• Females are usually unaffected
• Only mother can transmit the gene
• X-linked recessive diseases
• Ocular albinism
• Megalocornea
• Choroideremia
• Juvenile X-linked retinoschisis
• Fabry’s disease
• Hunter’s disease
• Red-green colorblindness
Lyonization
• X-inactivation
• One of the copies of the X chromosome in some cells of females is
inactivated
• Can result in expression of X-linked recessive disease in carrier
females
• Iris transillumination defects in female carriers of ocular albinism
• Areas of chorioretinal atrophy in females carriers of choroideremia
 Genes to remember
Disease Inheritance pattern Associated gene(s) or
chromosome
Axenfeld-Rieger AD PITX2, FOXC1
Pseudoexfoliation complex LOXL1
Aniridia 2/3 AD, 1/3 AR PAX6
Juvenile Open Angle Glaucoma AD TIGR/myocilin
Neurofibromatosis AD Chromosome 17
Von Hippel Lindau disease AD Chromosome 3
Retinoblastoma AR with AD phenotype Chromosome 13
Pharmacology
All of the following options are ways to increase the
amount of drug absorption from an eye drop except:

A. Prior administration of a topical anesthetic

B. Punctal occlusion
C. Increased lipid solubility
D. Increased hydrophilicity of the drug
Answer: D. Increased hydrophilicity of the drug
Basics
• 1 drop = 50 microL; the conjunctival sac holds 20-40 microL
• Barriers to corneal penetration
• The epithelium and endothelium or HYDROPHOBIC
(waterproof)/LIPOPHILIC
• The stroma is the opposite – HYDROPHILIC/LIPOPHOBIC
• How to increase absorption
• Add surfactant – disrupts epithelial integrity (e.g. benzalkonium chloride,
administer topical anesthetic)
• Punctal occlusion, lid closure – decreases drainage
• Increase lipid solubility of drug (more important than water solubility)
• Increase drop frequency
Basics
• Topical ophthalmic medications bypass hepatic ‘first-pass’
metabolism, unlike oral medications (cul-de-sac  nasolacrimal
duct  mucosa  bloodstream)
• Systemic effects
• Systemic medications must cross blood-ocular barrier (blood-
aqueous for anterior segment, blood-retinal for posterior segment)
• Concentration: 1% solution = 1 g / 100 mL
All of the following effects are seen when a
direct-acting cholinergic agonist is used except:

A. Miosis
B. Decrease in zonular tension
C. Increase in outflow facility
D. Decrease in accommodation
Answer: D. Decrease in accommodation
Atropine Pilocarpine
Mydriasis Miosis
Increases uveoscleral outflow Increases trabecular meshwork
outflow, decreases uveoscleral outflow
Relaxation of ciliary muscle Contraction of ciliary muscle
Loss of accommodation Induced myopia
Posterior shift of lens-iris diaphragm Anterior shift of lens-iris diaphragm
What is the correct order of
increasing mydriatic duration?
A. Homatropine, scopolamine, cyclopentolate, tropicamide
B. Atropine, homatropine, tropicamide, cyclopentolate
C. Tropicamide, homatropine, scopolamine, atropine
D. Atropine, homatropine, scopolamine, tropicamide
Answer: C. Tropicamide, homatropine, scopolamine,
atropine

• Tropicamide 4-6 hours

• Cyclopentolate 1-2 days
• Homatropine 3 days
• Scopolamine 4-7 days
• Atropine 7-14 days
List the following topical steroids in terms of ability to
elevate IOP in susceptible patients from most to least likely.

A. Prednisolone, hydrocortisone, dexamethasone, fluorometholone

B. Prednisolone, dexamethasone, hydrocortisone, fluorometholone
C. Difluprednate, fluorometholone, prednisolone, hydrocortisone
D. Difluprednate, prednisolone, fluorometholone, hydrocortisone
Answer: D. Difluprednate, prednisolone,
fluorometholone, hydrocortisone
• The IOP-elevating potential of a corticosteroid is related to its
potency.
What is the mechanism of action of
ciproflocaxin?
A. Inhibits DNA gyrase
B. Inhibits protein synthesis by binding to 30S ribosomal
subunit
C. Inhibits protein synthesis by binding to 50S ribosomal
subunit
D. Inhibits synthesis of folic acid
Answer: A. Inhibits DNA gyrase
• Fluoroquinolones (ciprofloxacin, ofloxacin) – inhibit DNA gyrase
• Tetracyclines (doxycycline) – inhibit protein synthesis by binding to
30S ribosomal unit
• Macrolides (erythromycin) – inhibit protein synthesis by binding to
50S ribosomal subunit
• Sulfonamides (sulfamethoxazole [the other half of trimethoprim])
– competitive antagonists of p-aminobenzenesulfonamide, which
disrupts the synthesis of folic acid
References
• All sample questions were taken from Chern KC, Saidel, MA.
Review Questions in Ophthalmology. 3rd ed. Philadelphia, PA:
Wolters Kluwer; 2015.
• Graphics are cited in the notes section of the same slide.
• Trattler WB, Kaiser PK, Friedman NJ. Review of Ophthalmology. 2nd
ed. Edinburgh, UK: Elsevier Saunders; 2012.