<ul>
 <li>Transparent, biconvex structure</li>
 <li>Contributes 10-15 dioptres to visual system</li>
 <li>Anterior curvature greater than posterior</li>
 <li>10mm diameter</li>
 <li>4mm thickness (3mm at birth and 6mm at age 80)</li>
 <li>35% water (normally)</li>
 <li>Lens proteins are mostly water soluble (except for MIP)</li>
 <li>Lens osmolality is greater than aqueous</li>
</ul>
<HotTopic>
 
 The lens is unique in having no innervation or vascularisation: relies wholly on aqueous and
 vitreous
 
</HotTopic>
## Embryology
<ul>
 <li>Lens placode develops from surface ectoderm at 27 days</li>
 <li>Invaginates into optic cup to form lens vesicle at 33 days</li>
 <li>
 Central lens pit produces hollow lens cavity (temporarily in communication with the amniotic
 cavity via the lens pore)
 </li>
 <li>Detaches from surface ectoderm and sinks below optic cup</li>
 <li>
 Development of the neural retina provides signals to induce formation of primary lens
 fibres&nbsp;
 </li>
 <ul>
 <li>These produce crystallins</li>
 </ul>
 <li>Fibres elongate towards the anterior lens epithelium and occupy lens cavity</li>
 <li>Nuclei migrate anteriorly to form lens bow with anterior convexity</li>
 <li>Secondary lens fibres develop at the equatorial zone of the anterior lens epithelium</li>
</ul>
<ul>
 <li>
 Embryonic and fetal nourishment is provided by the tunica vasculosa lentis: a vascular net which
 surrounds the lens from 9 weeks. Derived from anastomoses between:
 </li>
 <ul>
 <li>Hyaloid vessels posteriorly</li>
 <li>Pupillary membrane vessels from the long posterior ciliary arteries</li>
 </ul>
</ul>
## Capsule
<ul>
 <li>Thickened, smooth basement membrane produced by lens epithelium</li>
 <li>Variable thickness:&nbsp;</li>
 <ul>
 <li>Thinnest at the posterior poles (about 2 micrometers)&nbsp;</li>
 <li>
 Thickest anteriorly (about 15 micrometers) as the anterior lens benefits from the active
 epithelium which secretes capsular material throughout life: this is limited at the posterior
 lens
 </li>
 </ul>
 <li>
 Type IV collagen, GAGs, fibrillin, heparin sulphate, fibronectin
 </li>
 <li>Elastic</li>
 <li>
 Permeable to water, ions and small molecules or proteins up to the size of albumin (68,000 kD).
 </li>
</ul>
## Lens epithelium
<ul>
 <li>Only present anteriorly</li>
 <li>Simple cuboidal epithelium</li>
 <li>Mitosis produces new lens fibres: greatest activity at the equator</li>
 <li>Regulates the water and ion balance of the lens</li>
 <ul>
 <li>An Na/K ATPase pump removes sodium from the lens epithelium</li>
 <li>Highest concentration of the pump at the equator</li>
 </ul>
 <li>Cells elongate, sink below the superficial layer and nuclei migrate anteriorly (lens bow)</li>
</ul>
## Lens fibres
<ul>
 <li>
 Innermost primary lens fibres comprise the embryological nucleus: no cells are lost during life
 </li>
 <li>
 Fetal nucleus surrounds that, followed by the adult nucleus and the cortex (newest fibres)
 </li>
 <li>Gap junctions allow cell communication (via connexins) including ion movement</li>
 <li>Deepest, oldest fibres are anucleate</li>
 <li>
 Superficial fibres are rich in cell components eg. ribosome, polysomes and rough ER, to produce
 crystallins and also express the lens-fibre-specific major intrinsic protein (MIP)
 </li>
 <ul>
 <li>
 Note: all crystallins in the lens are water soluble except for main intrinsic polypeptide
 (MIP)
 </li>
 </ul>
 <li>
 Within the fetal nucleus, the ends of neighbouring fibres form anterior and posterior
 sutures&nbsp;
 </li>
 <ul>
 <li>Anterior is Y-shaped</li>
 <li>Posterior is inverted Y-shaped</li>
 </ul>
 <li>
 These most mature cells become terminally differentiated and the nuclei disintegrate as do other
 components including mitochondria (these organelles would scatter light and reduce visual acuity
 otherwise)
 </li>
</ul>
## Lens proteins
<ul>
 <li>33% of lens weight is protein</li>
 <li>Crystallins account for 90-95% of total protein (but aren&rsquo;t specific to the lens)</li>
 <ul>
 <li>Crystallins contribute the refractive index of the lens</li>
 <li>Unique characteristics</li>
 <ul>
 <li>Highly stable structure</li>
 <li>Remain soluble at high protein concentration so opaque clumps don&rsquo;t form</li>
 </ul>
 <li>Two main families</li>
 <ul>
 <li>Alpha</li>
 <li>Beta, gamma</li>
 </ul>
 </ul>
 <li>Protein synthesis occurs in peripheral lens cells and ceases as they become fibres</li>
 <li>Proteolysis is not a significant process since these proteins last for decades</li>
 <li>
 Calpains are &lsquo;endopeptidases&rsquo;: enzymes that degrade alpha and beta crystallins,
 actin and some membrane proteins. Calpain dysregulation has been implicated in cataract
 formation
 </li>
 <li>
 Ubiquitin binds to damaged proteins and facilitates their digestion (noted to be reduced in old
 lenses)
 </li>
 <li>
 Lens fibres are rich in microfilaments and microtubules: vimentin is the major intermediate
 filament in the lens cells
 </li>
</ul>
## Alpha-crystallin
<ul>
 <li>Largest lens protein: 30-40 subunits (of types alphaA and alphaB)</li>
 <li>Encoded by chromosomes 21 and 11.</li>
 <li>Undergo extensive post-translational modification</li>
 <li>These large molecules scatter light so transparency relies on a specific configuration</li>
 <li>Member of the &ldquo;heat shock protein&rdquo; family: inducible by heat and stresses</li>
 <li>Alpha-crystallin is a &lsquo;molecular chaperone&rsquo;:&nbsp;</li>
 <ul>
 <li>
 Protective of other proteins when they are vulnerable eg. prevents heat induced aggregation of
 proteins like beta-crystallin and prevents inactivation of glutathione reductase (hence why
 some proteins can survive for so long in the lens and it can remain transparent).
 </li>
 </ul>
</ul>
## Beta,gamma-crystallins
<ul>
 <li>No known function</li>
 <li>
 Gamma-crystallins are highly concentrated in old, hard lenses with no accommodative ability
 </li>
 <li>GammaD crystallin is the most abundant in the lens</li>
</ul>
## Major intrinsic polypeptide (aka aquaporin-0)
<ul>
 <li>Water insoluble lens specific protein component of fibre cell membranes</li>
 <li>As an aquaporin, functions as a water channel</li>
 <li>Function reduces with age</li>
 <li>AQP0 gene on 12q</li>
</ul>
## Lens biochemistry
<ul>
 <li>Sodium is low (~10mmol/L): removed by epithelial pump</li>
 <ul>
 <li>Sodium enters the lens from the vitreous, down a concentration gradient</li>
 <li>It is then pumped into the aqueous across the anterior epithelium</li>
 </ul>
 <li>Potassium is high (~120mmol/L)</li>
 <ul>
 <li>Potassium exits the lens down a concentration gradient into the vitreous</li>
 </ul>
</ul>
<HotTopic>
 Almost the reverse is true of aqueous
</HotTopic>
<ul>
 <li>When normal regulation of electrolytes fails:</li>
 <ul>
 <li>Potassium leaks out</li>
 <li>Sodium floods in</li>
 <li>Chloride follows the sodium</li>
 <li>And water follows the new osmotic gradient: entering the lens</li>
 </ul>
 <li>Entry of water disrupts transparency</li>
</ul>
<ul>
 <li>The Na/K ATPase maintains the normal balance of the lens by active transport</li>
 <ul>
 <li>
 Mainly at the anterior surface in epithelium and immature fibres with highest concentration at
 the equator
 </li>
 </ul>
 <li>ATP is generated in the anterior lens epithelial cells by anaerobic glycolysis</li>
 <ul>
 <li>Oxygen tension is low compared to other tissues</li>
 <li>Glucose is obtained from the aqueous and enters via GLUT1 (insulin-dependent)</li>
 <li>Anaerobic metabolism accounts for 80% of glucose consumption</li>
 <ul>
 <li>
 Only len epithelial cells possess mitochondria so this is the only place that aerobic
 metabolism (Kreb&rsquo;s cycle) can occur happen
 </li>
 <li>The lactic acid diffuses into the aqueous</li>
 </ul>
 <li>A small proportion of glucose is metabolised via the pentose phosphate pathway</li>
 <li>In conditions of excess glucose the sorbitol pathway occurs</li>
 </ul>
</ul>
<HotTopic>
 Glutathione is the most important antioxidant in the lens
</HotTopic>
<ul>
 <li>Amino acids are actively transported into lens</li>
 <ul>
 <li>But note that glutathione is a polypeptide synthesised in the lens</li>
 </ul>
</ul>
## Some causes of cataract
<ul>
 <li>Risk factors for age-related cataract</li>
 <ul>
 <li>African ethnicity</li>
 <li>Smoking</li>
 <li>Lower education level</li>
 <li>Female&nbsp;</li>
 </ul>
 <li>Oxidative modifications of lens proteins accumulate with age and contribute to</li>
 <ul>
 <li>Crystallin crosslinking&nbsp;</li>
 <li>Alterations in fluorescence</li>
 <li>Protein associated pigmentation</li>
 <li>Aggregations of lens proteins, light scattering and cataract</li>
 <li>
 Reduced glutathione levels (a scavenger of free radicals in the lens)
 </li>
 <li>Loss of alpha-A and gamma-S crystallins</li>
 </ul>
</ul>
<ul>
 <li>Specific causes:</li>
 <ul>
 <li>Statins</li>
 <li>
 Chlorpromazine and thioridazine (phenothiazines): pigment deposition on the anterior capsule
 </li>
 <li>PUVA/UV light: sun exposure is associated with cortical cataract</li>
 <li>Dehydration</li>
 <li>Alcohol</li>
 <li>Tobacco</li>
 <li>Poor nutrition</li>
 <li>Amiodarone and phenothiazines: anterior capsular, stellate cataracts</li>
 <li>Diabetes:</li>
 <ul>
 <li>
 Poorly controlled type 1 diabetes is associated with a snowflake cortical
 cataract and/or vacuolated cataract
 </li>
 <li>Adult-onset diabetes is associated with early onset age-related cataract</li>
 <li>
 Hyperglycaemia may be cause accumulation of sorbitol within cells (via aldose reductase),
 creating osmotic pressure and drawing water into the lens
 </li>
 <li>
 In younger patients associated with posterior subcapsular cataract especially in younger
 patients
 </li>
 </ul>
 <li>
 Galactosaemia: a deficiency in galactose-1-phosphate uridyltransferase
 (accumulation of galactitol in the lens):&nbsp;
 </li>
 <ul>
 <li>Autosomal recessive</li>
 <li>Systemic features: failure to thrive, hepatomegaly/liver failure, hypoglycaemia</li>
 <li>
 Bilateral oil-droplet cataracts
 </li>
 <li>Treatment is galactose-free diet</li>
 </ul>
 <li>Chronic hyperbaric oxygen usage: nuclear sclerotic cataracts</li>
 <li>Trauma: stellate posterior cataracts</li>
 <li>
 Atopic dermatitis: anterior subcapsular cataracts more common than posterior
 </li>
 <li>Retinitis pigmentosa: PSCC</li>
 <li>Myotonic dystrophy: Christmas tree cataracts</li>
 <li>
 Wilson&rsquo;s disease (and copper foreign bodies): green sunflower cataract
 </li>
 <li>Fuchs heterochromic cyclitis: unilateral cataract.</li>
 <ul>
 <li>
 Also associated with Amslers sign: bleeding from the angle after paracentesis due to fragile
 vessels crossing the angle
 </li>
 </ul>
 <li>Posterior polar cataract</li>
 <ul>
 <li>Associated with remnants of the vascular hyaloid system</li>
 <li>Autosomal dominant or sporadic</li>
 <li>Mapped to chromosome 16</li>
 <li>Increased risk of posterior capsule rupture</li>
 </ul>
 </ul>
</ul>

AC to Lens

Lens

Intro

FRCOphth Part 2 Study Notes

Tumours, masses and neoplasia

Tumours overview

Uveitis

Uveitis background

Anterior uveitis

Intermediate uveitis

Uveitis in JIA

Uveitis with JIA

Retinal vasculitis

Sarcoidosis

Behcet's disease

Toxoplasmosis

Strabismus

Overview

Viral uveitis

Esotropia

Fungal uveitis

Mycobacterial uveitis

Adnexal masses

Exotropia

Spirochaetal uveitis (including Syphilis)

Melanoma

Nematode uveitis

Retinoblastoma

Retinoblastoma (for Part 2)

Incomitent

Voyt-Koyanagi-Harada syndrome

Conjunctival intraepithelial neoplasia

Vertical deviations

Orbit and ocular adnexae

Orbit

Sympathetic ophthalmia

AV Malformations and hamartomas

Arteriovenous malformations and hamartomas

Restriction syndromes

Paediatrics

Leucocoria

Congenital Cataract

Paediatric Glaucoma

Retinopathy of prematurity

Retinopathy of Prematurity

ROP-like disorders

Congenital nasolacrimal duct obstruction

White dot syndromes

Aniridia: Short Arm 11 Deletion (11p13)

Choristomas

Management Of Amblyopia

Alphabet patterns

Iris Nodules

Scleritis

Meningioma

Strabismus surgery

Optic nerve glioma

Lymphoma

Extraocular Muscles

Rhabdomyosarcoma

Idiopathic orbital inflammation

Orbital neuroblastoma

Anterior Persistent Foetal Vasculature

Lacrimal system

Metastatic lesions

Surgical Retina

Retinal Detachment

Vitreoretinal Interface And Macular Hole

Epiretinal Membrane

Medical Retina

Diabetic Eye Disease

Orbital Blood Vessels

Retinal Vascular Disease

Macular Degeneration

Central Serous Chorioretinopathy (CSCR)

Sickle Cell Retinopathy

Retinitis Pigmentosa

Albinism

Retinal Telangiectasias

Miscellaneous Retinopathies

Atropine And Myopia Progression

Pharmacology

Side Effects Of Systemic Drugs

Foetal Alcohol Syndrome

Neuro-ophthalmology

Optic Neuropathy

Papilloedema

Idiopathic Intracranial Hypertension

Chiasmal Disorders

Retrochiasmal Disorders

Migraine

Paranasal Sinuses

Supranuclear Motility Disorders

Third Nerve Palsies

Fourth Nerve Palsies

Sixth Nerve Palsies

Seventh Nerve Palsies

Anisocoria

Myasthenia Gravis

Myopathies

Blepharospasm

Functional Visual Loss

Lacrimal Glands

Phakomatoses

Developmental diseases

Tear Film

Eyelids

Blinking

Lid Malpositions

Anterior segment - ocular surface

Conjunctiva

Conjunctivitis

Sclera

Pigmented Conjunctival Lesions

Squamous Cell Carcinoma Of The Conjunctiva

Ocular Cicatricial Pemphigoid

Cornea

Corneal Structure And Development