1.The lipid layer ; secreted by the the ~ 30 Meibomian glands in the inner leaflet of the eyelid. This layer prevents evaporation of the tear film and lubricates the eyelid.

2.The aqueous layer ; constitutes 90% of the thickness of the tear film and provides oxygen and nutrition for the cornea. This layer also has antibacterial properties and washes away debris. It is secreted by 2 kinds of lacrimal glands:

-The main lacrimal gland in the anterolateral portion of the roof of the orbit

This gland is responsible mainly for reflex tearing,but was found recently to contribute to basal tear secretion also.

-The acccessory lacrimal glands of Krause and Wolfring located mainly in the superior fornix.They are responsible for basal tearing .

3.The mucus layer ; secreted by goblet cells distributed throughout the bulbar and

palpebral conjunctiva.This hydrated glycoprotein layer makes the corneal surface

hydrophyllic and thus wettable and decreases surface tension of the tear film.

A deficiency in "2" results in a +ve Schirmer test. (Ex: Sjogren’s syndrome)

A deficiency in "3" results in a +ve Break up time test(Ex: Stevens-Johnson’s)

-transparent anterior 1/6^th of the globe
-vertical diameter ~ 11mm, horizontal ~ 11.7mm
-central thickness 0.5mm, 1mm peripherally
-axial refractive power of 43 diopters
-avascular, oxygen supply mainly from the tear film,metabolic requirements from the aqueous humor.
-composed of 5 distinct histologic layers:

1.Epithelium
2.Bowman’s layer
3.Stroma
4.descemet’s membrane
5.endothelium

1.Epithelium: 

-Non keratinized stratified squamous type of epithelium

-thickness of ~60Um.

-itself is 4 layers thick:

a. superficial layer of flattened cells rich in 64D keratin (not found in skin).

b. intermediate layer of polyhedral cells called wing cells.

c. basal germinal layer(one cell thick) .Here the columnar cells regenerate by mitosis,move superficially,become flatter,more keratinized and then are shed after seven days.This process also happens in wound healing.

d. basement membrane of the germinal layer ; PAS +ve, type IV collagen,firmly attached to bowman’s layer.(A disturbance at this level results in recurrent corneal erosion syndrome)

2. Bowman’s layer : 
-acellular anterior condensation of the corneal stroma. (Does not regenerate after injury).

3.Stroma: 
-or substantia propria, 90% of thickness of cornea

-mostly type I collagen (55%) and type VI (35%)

-composed of ~ 300 lamella of collagen fibrils of uniform diameter and regular spacing. Fibers in any one lamellae are parallel but perpendicular to fibers in adjacent lamellae.

- ground substance is made up of proteoglycans (keratan and chondroitin sulfate)

4. Descemet’s membrane : 

-PAS +ve glassy basement membrane of the endothelial cells
-Does regenerate after injury
-Forms at the periphery the line of Schwalbe, referred to clinically when
  assessing the the anterior chamber by gonioscopy.

           5. Endothelium: 
                -a single layer of flattened cells facing the anterior chamber

                -highly active in maintaining corneal transparency by regulating the water content

                 of the corneal stroma and ion transport via Na-K pumps.

                -a minimum of 700 cells/mm2 is required for endothelial integrity function

                 and metabolism

Clinical pearls

1. Physical or metabolic damage to the endothelium leads to corneal swelling,overhydration and opacification. For example,after cataract surgery,the corneal stroma is overhydrated and fluid may collect in small cysts thus the naming pseudophakic bullous keratopathy.In many instances,physycians use hypertonic saline (3-5 % NaCl) for deturgescence of swollen cornea.
2. Specular microscopy is a modality used to measure endothelial cell density,size and morphology. In corneal transplantation, an eligible corneal graft is one that has a minimum of ~1500 cells/mm2.
3. Keratometry mesures the average corneal curvature of the central 3mm along the vertical and horizontal meridians.Clinically used to calculate the power of the IOL(intraocular lens) needed to replace the cataractous one being extracted.
4. Keratoscopy provides a color-coded topographical map of the whole cornea.

Useful in the management of keratoconus,irregular and severe astigmatism…

   5. Pachymetry provides measurement of the central corneal thickness,useful in the diagnosis and monitoring of several
       corneal pathologies.

-volume ~ 0.6ml, turnover every 100minutes.

-main metabolic supply for the cornea and lens.

-secreted actively by the non- pigmented innermost layer of the ciliary processes of the ciliary body.

-osmolarity ;same as plasma

-glucose ; 80% of plasma glucose

-proteins ; 1% of plasma ,mostly albumins

-lactate,ascorbate and chloride ;higher concentration than in plasma.

-The alb/glob ratio in aqueous is usually higher than in plasma because the heavy globulins are excluded; in Retinoblastoma,the globulin content of aqueous increases so the ratio A/G decreases,as opposed to all non neoplastic and/or inflamatory conditions.

-The aqueous is thoroughly inspected on slit lamp examination for gaging the activity of ocular diseases such as uveitis; abundance of cells(mostly lymphocytes) and the presence of significant glare in the anterior chamber(reflecting protein exudation) indicates high disease activity thereafter affecting management and prognosis.

Clinical pearls

-The limbus can be involved in many ocular diseases,ex:

In vernal catarrh(allergic conjunctivitis), whitish elevations containing eosinophils are seen at the limbus and called Trantas dots.

In late stage trachoma (caused by chlamydia trachomatis),a unique feature is the presence of limbal follicles which on resolution leave characteristic yellowish brown depressions

called Herbert’s pits.

-thin translucent mucous membrane that starts at the limbus and covers the sclera (bulbar conjunctiva) and the inner surface of the eyelid (palpebral conjunctiva).

-statified columnar epithelium 3-7 layers thick,never keratinized normally.

-contains goblet cells that secrete the mucin layer of the tear film

-contains the accessory lacrimal glands of Krause and Wolfring(basal secretion)

-In viral conjunctivitis , numerous lymphoid follicles are observed in the lower eyelid.

-In vernal keratoconjunctivits,giant papillae having a cobblestone appearance are usually seen in the upper eyelid.

-Soft contact lens wearers may also develop GPC (giant papillary conjunctivitis).

-Excessive exposure to outdoor conditions especially UV radiation along with heat,dust and wind, may lead to degenerative conjunctival changes, two of which are:

1.pingueculum: a raised yellowish patch of elastotic degeneration that abutts but does not

encroach upon the cornea,usually nasally.

2.pterygium: a raised triangular area of bulbar conjunctiva which actively invades the cornea,usually from the nasal side to produce visual symptoms .It may be surgically removed if it is reaching the central pupillary area affecting vision, if it is causing astigmatism,recurrent inflammation,affecting motility,or even for mere cosmetic reasons.

-White of the eye, posterior five sixths of the globe.

-Irregular size and arrangement of collagen fibrils.

-Thickness is 1 mm posteriorly near the optic nerve and 0.3 anteriorly

where the EOM attach.

-The posterior scleral foramen is a canal which transmits the optic nerve,the central retinal artery and vein,and the sympathetic plexus to eye.This canal is 2 -3 mm in diameter and is bridged by a sieve-like structure called the lamina cribrosa.

-The sclera can be subdivided into 3 layers:

1.episclera: external layer,loose connective tissue adjacent to the periorbital fat,well vascularized

2. sclera proper:also called tenon’s capsule. It is the dense investing fascia of the eye composed of dense type I and III collagen. Avascular.

3.lamina fusca: the inner aspect of the sclera,located adjacent to the choroid and contains thinner collagen fibers and pigment cells.

Episcleritis is a benign self limiting inflammation common in young adults.

May be bilateral ,diffuse or nodular.

Symptoms:redness and mild discomfort. Unlike scleritis, photophobia and severe pain are unusual in episcleritis.

Usually blanching of the red eye occurs with phenylephrine (unlike scleritis)

Treatment with steroids or NSAIDS.

Scleritis: more serious and destructive than episcleritis

Severe pain and photophobia and even visual disturbances are common.

Deep red coloration with bluish hue,no blanching with phenylephrine.

Usually associated with systemic conditions(inflammatory, autoimmune ,C.T diseases)

Treatment: systemic and topical NSAIDS and steroids .

1.stroma : a thin avascular layer with fibroblasts and melanocytes.Heavily pigmented in persons with brown eyes,less pigmented in green and hazel irises,and least in blue.

Posteriorly,the stroma contains the sphincter pupillae muscle(parasympathetic,miosis)

2.Pigment epithelium: consists of 2 layers of cells:
-anterior layer which intermingles with the dilator pupillae musle(sympathetic,mydryasis)
-posterior layer which is continuous with the pigment epithelium of the ciliary body and RPE of the retina, all having same embryologic origin.
  
  

-the color of the eye depends on the degree of pigmentation in the anterior stroma

Abnormal hyperpigmentation may result in iris hyperchromia,nevi and melanomas.

-albinos have deficiency in the enzyme tyrosinase essential for melanin production,so they have deficient iris pigmentation demonstrable by its retroillumination through the pupil.The choroid and retina are also hypopigmented in albinos.

-Rubeosis irides is a clinical sign referred to in advanced diabetes; starting at the pupillary boder, neovessels proliferate and migrate centrifugally .Occasionally,the vessels reach the angle and obstruct the meshwork thereby causing neovascular or red glaucoma.

-In uveitis (inflammation of the middle coat of the eye),the iris may show pathognomonic granulomatous nodules at the pupillary border(Koeppe’s) and in its center(Busacca’s)

-in 95% 0f patients with neurofibromatosis,small bilateral melanocytic hamartomas are found on the surface of the iris,called Lisch nodules.

-transparent biconvex structure held in position by the ciliary zonules (of Zinn).

-very rich in proteins (35% w/w),mostly beta-crystallins, the insoluble portion of which increases with age contributing to cataract formation.

-metabolism is mainly anaerobic, glucose and nutrients from aqueous humor

-composed of 6 layers from anterior to posterior:

1.anterior capsule: basement membrane of the anterior epithelium(thickest BM in body)

2.anterior epithelium:single row of cuboidal cells responsible for metabolism of the whole lens

3. anterior cortex

4.central nucleus

5.posterior cortex

6.posterior capsule

Cataract is the most common pathologic change in the lens,can affect any and all its layers and can have different etiologies.

- Patients with posterior subcapsular cataract are particularly troubled by sunlight and headlights of incoming cars,and might have their near vision diminished. Common causes of PSC are aging,trauma or steroid intake.

-Nuclear cataract(age-related,senile)  causes myopic shift by increasing the refractive index of the lens,so elderly patients  who had been wearing presbyopic lenses  may once again be able to read without spectacles.

-Anterior subcapsular catacract is often associated with atopy.

-PAM or potential acuity meter is a device used to assess the maximum potential vision that could be achieved if media opacities,like cataracts, are removed. The device shines a bright and focused beam of light that can make its way through opacities,  to the macula, thus unmasking any potential visual reserve.

 -extends for 6mm from the end of the retina (ora serrata) till the scleral spur.

 -its epithelial portion ( adjacent to vitreous ) consists of a posterior portion (pars plana) and an     anterior portion (pars plicata).The latter has 60-70 folds called the ciliary processes which secrete the aqueous humor into the posterior chamber. 

-The pars plana is the area through which surgical instruments are usually introduced.

-its uveal portion have the ciliary muscle which has 3 parts,all under parasympathetic innervation:

1.longitudinal (outermost)

2.radial

3.circular

Contraction of the radial and circular muscles relaxe the zonules allowing for increased curvature of the lens ,thereby increasing its refractive power in the process of accomodation (near vision)

Contraction of the longitudinal muscle stretches mainly the choroid but also applies forces on the scleral spur thereby opening  the canal of schlemn and facilitating the aqueous drainage.Pilocarpine is a cholinergic drug clinically used to decrease intraocular pressure in glaucoma patients, by the above mechanism.

The zonules:

- hold the lens in position immediately posterior  to the iris.
-extend from the basal lamina of the NPE of the ciliary process and insert into the capsule at the equator of the lens.
-composed of pure fibrillin.
-referred to as tertiary vitreous.

-dark brown vascular sheet,0.25mm thick, lying between the sclera and the retina.

-outer vascular bed have large vessels (layer of Haller)

- inner bed consists of an extensive network of fenestrated vessels, the choriocapillaris which is the major blood supply to the outer layers of the retina and to the whole macula .(The inner layers, up to  the middle of the EPL are supplied by the central retinal artery.

- Being rich in melanocytes,the choroid may be the site of benign choroidal nevi and  maligant choroidal melanoma which is the most common intraocular tumor in adults.

-a relatively thin (1-4Um) and refractile connective tissue membrane lying between the choriocapillaris of the choroid and the RPE of the retina.

-also called lamina vitrea.

- composed of 5 different layers by electron microscopy:

1 .(innermost) :basement membrane of the RPE.

2.  a layer of collagen fibers.

3.  a layer of elastic fibers.

4.  another layer of collagen fibers

5. (outermost): basement membrane of  the endothelial cells of choriocapillaris.

-In AMD (age related macular degeneration),which is the most common cause of blindness above 65 years of age, there are yellow depositions in Bruch’s membrane called drusens,usually at the macula.

-Most internal layer of the eye,  facing the vitreous.

-ends at the ora serrata anteriorly.

-consists of 2 basic layers

1.neural retina: inner layer, itself has 9 layers including the photoreceptor layer.

2.RPE(retinal pigment epithelium):outer layer that rests on Bruch’s membrane &choroid.

Clinical pearls

-The neural retina and RPE arise from distinct embryologic layers and the potential space in between is the site of retinal detachment. RD is a clinical emergency because the blood supply of the outer retina and the macula is from the choroid ,which in RD ,is detached and remote.

-RPE cells provide metabolic and functional support to the photoreceptors.They are versatile cells that can transform into more primitive mesodermal cells,fibroblasts,myoepithelial and angioblastic cells and can contribute to pathologic processes like CNVM ( choroidal neovascular membrane)of myopes and AMD, and PVR (proliferative vitreoretinopathy) of RD.

-Photoreceptors are the outermost layer of the sensory retina,  andare divided into:

1.cones : responsible for color vision and daytime high discrimination vision, They are highly concentrated at the fovea.

2. rods : responsible for night vision (black and white) cruder perception and less resolution.

-Retinoschisis is fluid accumulation within the neurosensory retina to form intraretinal cysts.It may progress to retinal tears and retinal detachment.

-Retinal dialysis is caused by dynamic vitreoretinal traction usually at the  inferotemporal ora serrata (or superonasal in case of trauma).It is similar to a flap tear exept that the vitreous gel is attached to the posterior rather than the anterior margin of the tear.

-largest chamber of the eye (4.5ml).

-transparent gel composed of random network of thin collagen fibers in a highly dilute solution of salts, proteins and hyaliuronic acid (99% water)
-The vitreous adheres firmly to the margin of the optic disc  and to the peripheral retina at the ora serrata and the pars plana(vitreous base)

Clinical pearls

-With age, the gel component of the vitreous degenerates and liquifies (syncherisis senilis), collagen fibers tend to aggregate and fluid may detach the gel from the retina, starting a PVD (posterior vitreous detachment).The patient’s symptoms include photopsia or flashes of light ( implying traction on the retina) and floaters frequently described as black flies .PVD has a benign natural course usually, but may progress and cause retinal tears and detachment in approximately 10% of patients.
-Sometimes the epipapillary glial tissue can become avulsed from the disc margin during PVD,and the patient’s  floateris described as  a cobweb or a spider, moving with the eye. In such cases ,ophthalmoscopy reveals a small ring of tissue swirming above the optic nerve head, called Weiss ring.

The optic nerve

-formed by the axons of the 1.2 million ganglion cells while exiting the eye.

-contains within its fibers the central retinal artery and the central retinal vein which

emerge from a central depression called the  physiologic cup 

-can be divided into 4 portions:

1.intraocular : itself is divided into

-optic nerve head = optic papilla=optic disc with diameter of 1.5mm
-prelaminar portion, anterior to the lamina cribrosa
-laminar, within the lamina cribrosa
-post laminar,posterior to the lamina cribrosa

2. intraorbital portion extending from the globe until the apex of the orbit

3.intracanalicular portion within the optic canal.

4.intracranial portion that merges into the optic chiasm and  then optic tract.

Clinical pearls

The optic disc is a major ophthalmoscopic landmark of the ocular fundus. Special attention is given to the color, the margins, the cup to disc ratio and the neuroretinal rim.

A healthy ONH (optic nerve head) is a yellowish pink one,with distinct well defined margins,nonelevated, with a cup to disc ratio of less than 0.3.

-ONH has blurred margins in papilledema, which is disc edema secondary to an elevated intracranial pressure,as in space occupying tumors, meningitis... The  mechanism is the following :  the central retinal vein pierces the dural sheathing of the optic nerve ~ 12mm behind the globe and courses  in the subarachnoid space before heading to the globe.Here ,the increased ICP exerts external compressive pressure on the vein.Elevated venous pressure is in turn transmitted backward to the optic disc to cause swelling ,elevation,and ,in severe cases, hemorrhages and cotton wool spots ( infarcts in the nerve fiber layer )).

The nasal margin is the first to blur in papilledema, the last being the temporal.

The latest stage of papilledema is atrophic, where the disc is white , no hemorrhages or infarcts seen.This is called secondary optic atrophy (atrophy after swelling).

-In glaucoma, there is increased cup to disc ratio.C/D which is usually < 0.3, can go up to 0.7, 0.8,  or even to subtotal or total cupping.

-In diabetes, when the retinopathy advances to its proliferative stage, numerous fragile neovessels can be seen over the optic disc. Such a subtle sign can warrant intervention like PRP(panretinal photocoagulation),by which a laser beam is used to "ablate" the ischemic retina secreting the angiogenic factors.Usually PRP is done peripherally in hope to decrease neovascularisation in the posterior pole including  the ONH  and  macula.

-Hyperopia is associated with  a small ONH ,myopia with  a large ONH.

-The blood supply of the optic nerve is derived from several sources:

    1. The surface of the optic disc recieves capillaries from the central retinal artery.

    2. The prelaminar and laminar portions receive capillaries from the ~12 short posterior ciliary        arteries that penetrate thesclera and make the anastomotic circle of Haller-Zinn. Occlusion of these vessels and infarction of the nerve causes    AION (anterior ischemic optic neuropathy).The patient presents with sudden  and painless loss of vision,mostly an altitudinal   defect affecting the inferior visual field.