2 - Intraocular Pressure and Aqueous Humor Dynamics

Question 1

Goldmann Equation

Answer 1

1. Summarizes relationship between the many factors contributing to aqueous flow through TM and uveoscleral pathway

Question 2

Aqueous Humor Production and Composition

Answer 2

1. Produced at rate of 2-3 microLiter/min
2. 80 ciliary processes with double layer of epithelium and stroma with rich supply of capillaries from major arterial circle of the iris
3. Apical surfaces of inner nonpigmented and outer pigmented face each other
4. Inner nonpigmented → tight junctions important component of BLOOD-AQUEOUS barrier. With many mitochondria and microvilli and where AQUEOUS HUMOR PRODUCED
5. 3 mechanisms of Aq production:
   
   1. Active Secretion → E requiring against electrochemical gradient. Independent of pressure and MAJORITY of production occurs via active secretion. Involves carbonic anhydrase II
   2. Ultrafiltration → Pressure-dependent along pressure gradient
   3. Simple Diffusion → passive movement of ions based on charge and concentration
6. Composition:
   
   1. Excess H+, Cl-, ascorbate compared to plasma
   2. Deficient bicarbonate, protein (essentially protein free = 1/200 - 1/500 reflecting intact blood-aqueous barrier and allowing for optical clarity → albumin 1/2 of protein present) relative to plasma
   3. carbonic anhydrase, growth factors, lysozyme, diamine oxidase, plasminogen activator, dopamine B-hydroxylase, phospholipase A2, prostagalndins, cAMP, catecholamines, steroid hormones, hyaluronic acid
7. Composition changes as aq humor flows from PC, through pupil, and into AC 2/2 to dilutional exchanges and active processes

Question 3

Suppression of Aqueous Humor

Answer 3

1. Inhibition of Carbonic Anhydrase suppresses aq humor formation
2. Blockade of þ-2 receptors may affect active secretion by decreasing Na+,K+-ATPase pump
3. Stimulation of alpha-2 reduces aq humor formation by inhibiting cAMP

Question 4

Aqueous Humor Formation

Answer 4

1. Fluorophotometry → measures rate of aq humor formation; fluorescein administered systemically or topically and gradual dilation in AC measured optically and change in fluorescein concentration over time used to calculate aq flow
2. 2-3 microLiter/min
3. Varies diurnally; DECREASES by 1/2 during SLEEP
4. Affected by:
   
   1. Integrity of blood-aqueous barrier
   2. Blood flow to ciliary body
   3. Neurohumoral regulation of vascular tissue and ciliary epithelium
5. Decreases with:
   
   1. Age
   2. Trauma
   3. Intraocular inflammation
   4. General anesthetics, some systemic hypotensives
   5. Carotid occlusive disease

Question 5

Trabecular Outflow

Answer 5

1. 3 layers of TM each consists of collagenous connective tissue covered by endothelial cell layer
   
   1. Juxtacanalicular → Major site of outflow resistance & forms inner wall of Schlemm canal
   2. Corneoscleral
   3. Uveal
2. Aqueous moves both across and between endothelial cells lining inner wall of Schlemm canal
3. TM = pressure-sensitive outflow and 1-way valve, independent of energy. Cells are phagocytic and demonstrate this function in presence of inflammation and after laser trabeculoplasty
4. Most adult eyes → trabecular cells contain pigment granules within cytoplasm giving meshwork a brown or muddy appearance. 200k-300k trabecular cells per eye; with age #trabecular cells decreases and basement membrane thickens potentially increasing outflow resistance.
   
   1. Laser trabeculoplasty → changes extracellular matrix
5. Schlemm canal → lined with an endothelial layer on a discontinuous basement membrane, single channel 200-300 micrometers and traversed by by tubules; Schlemm canal → episcleral veins → anterior ciliary and superior ophthalmic veins → cavernous sinus.
6. Increasing IOP → Schlemm canal decreases in cross-sectional area while TM expands
7. Outflow facility (C in Goldmann equation) inverse of outflow resistance and varies widely in normal eyes; outflow decreases with age, surgery, trauma, medications, endocrine factors, patients with glaucoma; tonography → measures facility of aqueous outflow using weighted Schiotz tonometer on K elevating IOP and outflow facility computed at rate at which pressure declines with time.

Question 6

Uveoscleral Outflow

Answer 6

1. Pressure-insensitive
2. AC → ciliary muscle → supraciliary and suprachoroidal spaces → exits eye through intact sclera and vessels that penetrate it
3. ~45% of total aqueous outflow
4. Decreases with age, reduced in patients with glaucoma, miotics
5. Increases with cycloplegia, adrenergic agents, prostaglandin analogs, cyclodialysis clefts
6. Calculated from Goldmann equation noninvasively

Question 7

Episcleral Venous Pressure

Answer 7

1. Stable except with alterations in body position and with certain diseases that obstruct venous return to heart or shunt blood from arterial to venous system
2. Increased:
   
   1. Sturge-Weber
   2. Carotid-cavernous sinus fistulas
   3. Cavernous sinus thrombosis
   4. Elevated IOP in thyroid eye disease
3. Usual 6-9 mmHg
4. Abnormally elevated EVP can cause collapse of Schlemm canal and potentially increase aqueous humor outflow resistance and may alter uveoscleral outflow → thus change in IOP may be greater or less than that predicted by Goldmann equation

Question 8

IOP Factors

Answer 8

1. IOP has a non-Gaussian distribution with a skew toward higher pressures, especially in patients older than 40 years
2. Increased:
   
   1. Recumbent vs upright due to increase in EVP
   2. Genetics in patients with fmaily hx of POAG
   3. Sleep during early-morning hours (outside of clinic times)
3. Decreased:
   
   1. Cannabis → short duration
   2. Alcohol
4. IOP varies by 2-6 mmHg over 24-hour period in patients
5. Tonometry → Based on P = F/A
   
   1. Goldmann applanation tonometer → measures forces necessary to flatten an area of K 3.06mm in diameter → resistance of K to flattening at this diameter counterbalanced by capillary attraction of tear film meniscus to tonometer head. IOP = flattening force x 10
6. Corneal hysteresis → difference in IOP measured during initial corneal indentation and IOP measured during corneal rebound; reduced corneal hysteresis may be risk factor for glaucoma

Question 9

Tonometry Factors

Answer 9

1. Increased:
   
   1. Excessive fluorescein resulting in wide mires
   2. K scarring
   3. Thick K (resist deformation)
2. Decreased:
   
   1. Inadequate fluorescein
   2. K edema
   3. CL
   4. Thin K (LASIK and PRK and other refractive procedures). Risk factor for progression from ocular HTN to glaucoma due to underestimating actual IOP or whether thin k independent risk factor undetermined
3. K astigmatism → both; take 2 pressure readings taken 90 degrees apart and average

Question 10

Tonometry Types

Answer 10

1. Noncontact air-puff tonometers → IOP overestimated

Question 11

Tonometry Cleaning

Answer 11

1. Prisms should be soaked in:
   
   1. 1:10 sodium hypochlorite (household bleach)
   2. 3% hydrogen peroxide
   3. 70% isopropyl alcohol for 5 minutes then rinsed and dried to prevent damage to K epithelium