Posterior segment

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11 Posterior segment

Anatomy

Vitreous

Composed of 99% water and a few type II (mainly) and type IX collagen fibers; viscous, gel-like quality from mucopolysaccharide and hyaluronic acid that is folded into coiled chains and holds water like a sponge; volume ∼4 cm³; syneresis (liquefaction) occurs with aging (Figures 11-1, 11-2).

Figure 11-1 Vitreous anatomy according to classic anatomic and histologic studies.

(From Schepens CL, Neetens A: The Vitreous and Vitreoretinal Interface. New York, Springer-Verlag, 1987.)

Figure 11-2 Ultrastructure of hyaluronan–collagen interaction in the vitreous. C, collagen; IF, interconnecting filament.

(Courtsey of Dr Akiko Asakura. From Askura A: Histochemistry of hyaluronic acid of the bovine vitreous body as studied by electron micoscopy. Acta Soc Ophthalmol Jpn 89:179–191, 1985.)

Vitreous base

portion of vitreous that attaches to peripheral retina and pars plana; 6 mm width – 2 mm anterior and 4 mm posterior to the ora serrata; straddles ora serrata; avulsion is pathognomonic for trauma

Vitreoretinal junctions

arise from footplates of Müller’s cells at internal limiting membrane; provide firm vitreoretinal attachment, especially at vitreous base, macula, optic nerve, and retinal vessels; also at edge of lattice degeneration, chorioretinal scars, degenerative remodeling, enclosed oral bays; weak attachments at fovea and disc, and over areas of lattice

Retina (Figure 11-3)

Neurosensory Retina (9 Layers)

Inner refers to proximal or vitreous side of retina

1 Internal limiting membrane (ILM): foot processes of Müller’s cells (PAS-positive basement membrane); true basement membrane; clinically visible as small yellow-white spots (Gunn’s dots) at ora serrata; continuous with inner bordering membrane of ciliary body

2 Nerve fiber layer (NFL): unmyelinated ganglion cell axons; also contains glial cells (astrocytes); myelination by oligodendrites occurs at lamina cribrosa; axons synapse with nuclei of cells in LGB

3 Ganglion cell layer: usually a single cell layer with cells packed tightly near the optic disc and more scattered in the periphery; nuclei are multilayered in macula

4 Inner plexiform layer: synaptic processes between bipolar and ganglion cells, as well as amacrine with bipolar cells; outermost layer completely nourished by retinal arteries

5 Inner nuclear layer: outermost retinal layer; inner

of retina receives its nourishment from retinal vasculature (outer

from choroid); contains cell bodies of bipolar, amacrine (confined to inner surface), horizontal (confined to outer surface), and Müller’s (span from ILM [foot processes] to ELM [microvilli, which point toward RPE]) cells

6 Outer plexiform layer: synaptic processes between photoreceptors and dendritic processes of bipolar cells; cone axons = Henle fibers

Middle limiting membrane (MLM): synapses; forms approximate border of vascular inner portion and avascular outer portion of the retina

Central retinal artery supplies retina internally (MLM to ILM)

Choriocapillaris supplies retina externally (MLM to RPE)

Interior to MLM: dendrites of bipolar cells along with horizontally coursing processes of horizontal cells

External to MLM: basal aspect of photoreceptors

In macula, outer plexiform layer is called Henle’s fiber layer; radial orientation of fibers (responsible for macular star configuration and cystic spaces in cystoid macular edema)

7 Outer nuclear layer: photoreceptor cell bodies and nuclei; most cone nuclei lie in single layer immediately internal to ELM

8 External limiting membrane (ELM): fenestrated intercellular bridges, situated external to photoreceptor nuclei; interconnects photoreceptor cells to Müller’s cells; not a true basement membrane but an illusion caused by tight junctions between Müller’s cells and photoreceptors

9 Photoreceptor layer: rods and cones; number equal in macula; 11-cis retinal converted to all-trans retinol in PR outer segments (not in RPE where it is converted back) (Figure 11-4)

100 million rods: rods account for 95% of photoreceptors; rhodopsin; density maximal in a ring 20–40° around fovea; when dark adapted, rods are 1000 times more sensitive than cones; rod disks are not attached to cell membrane, discrete structures; provide dark adapted vision

5 million cones (50% in macula): 3 types of visual pigment (blue [make up only 10%], green, red); density maximal in fovea; cone disks are attached to cell membrane and undergo membranous replacement; provide high acuity and color vision

Figure 11-3 Normal fundus as seen through indirect ophthalmoscope.

(From A Manual for the Beginning Ophthalmology Resident. 3rd edn, edited by James M. Richard. 1980, p. 122 Figure 60.)

Figure 11-4 Neuronal connections in the retina and participating cells.

(From Schubert HD: Structure and function of the neural retina. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Peripheral Retina

Extends from macula to ora serrata, nonpigmented epithelium is contiguous with pars plana; defined as any area of the retina with a single layer of ganglion cells (Figure 11-5)

Figure 11-5 Transition of neural retina to nonpigmented epithelium at the ora serrata.

(From Schubert HD: Structure and function of the neural retina. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Macula

Area of retina in which ganglion cell layer is more than 1 cell thick (5–6 mm in diameter)

Centered 4 mm temporal and 0.8 mm inferior to optic nerve

Differentiation of the macula does not occur until age 4–6 months old

Predominantly red and green cones in macula

High levels of carotenoids (100-1000× more than anywhere else): lutein (antioxidant) and zeaxanthin (light screening)

Fovea (Figures 11-6, 11.7)

Central depression of inner retinal surface (1.5 mm in diameter) within macula

Figure 11-6 Foveal margin, foveal declivity, foveola, and umbo.

(From Schubert HD: Structure and function of the neural retina. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Figure 11-7 Normal fundus with macula encompassed by major vascular arcades.

(From Schubert HD: Structure and function of the neural retina. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Corresponds to the foveal avascular zone (FAZ)

Contains taller RPE cells and xanthophyll pigment (blocks choroidal fluorescence during fluorescein angiography)

Initially, ganglion cell nuclei are present in fovea but are gradually displaced peripherally, leaving fovea devoid of accessory neural elements

(From Fryczkowski AW: Anatomical and functional choroidal lobuli. Int Ophthalmol 18:131–141, 1994.)

Blood supply from 1–2 long and 15–20 short posterior ciliary arteries (from internal carotid to ophthalmic artery)

Endothelium is permeable to large molecules

Choriocapillaris arranged in segmental pattern; major source of nutrition for RPE and outer retinal layers

Drains via vortex veins to superior and inferior ophthalmic veins

Contain both parasympathetic and sympathetic nerves (autoregulatory function to keep blood flow constant) via short (mainly) and long posterior ciliary nerves

Physiology

Visual pigments

4 types, each composed of 11-cis-retinal (vitamin A aldehyde) + a protein (opsin); 3 cone pigments and 1 rod pigment (Table 11-1)

Table 11-1 Visual pigments

Photoreceptor	Pigment	Peak sensitivity
Rod	Rhodopsin	505 nm
Red cones	Erythrolabe	575 nm
Green cones	Chlorolabe	545 nm
Blue cones	Cyanolabe	445 nm

Rod photoreceptor membranes

lipid bilayer in which rhodopsin is an integral component

Chromophore 11-cis-retinaldehyde is oriented parallel to the lipid bilayer (perpendicular to the path of photons)

Bleaching releases all-trans-retinaldehyde from the visual pigment (opsin) with conversion to all-trans-retinol; this initiates an electrical impulse that travels to visual cortex; rhodopsin is then resynthesized, and vitamin A is stored in liver and transported to RPE by serum retinol–binding protein and prealbumin

Rods shed outer segments during the day

Cones shed outer segments during the night

Luminosity curves

Light-adapted: cone peak sensitivity is to light of 555 nm; yellow, yellow-green, and orange appear brighter than blue, green, and red

Dark-adapted: rod peak sensitivity is to light of 505 nm (blue)

Purkinje shift: shift in peak sensitivity that occurs from light- to dark-adapted states (Figure 11-9)

Figure 11-9 Normal dark-adaptation curves measuring retinal sensitivity to a small spot of light whose intensity is varied until the threshold value is found; a 2° test spot was placed at different distances from the foveal center. Note the cone–rod break at 9 minutes, middle graph.

(From Hecht S, Haig C, Wald G: The dark adaptation of retinal fields of different size and location. J Gen Physiol 19:321–337, 1935.)

Electrophysiology

Electroretinogram (ERG)

Measures mass retinal response; useful for processes affecting large areas of retina

Photoreceptors, bipolar and Müller’s cells contribute to flash ERG; ganglion cells do not

Light is delivered uniformly to entire retina, and electrical discharges are measured with a corneal contact lens electrode

Components (Figure 11-10)

a-wave: photoreceptor cell bodies (negative waveform)

b-wave: Müller’s and bipolar cells (positive waveform)

Amplitude: bottom of a-wave to top of b-wave; measured in microvolts

Measures response of entire retina; proportionate to area of functioning retina

Decreased in anoxic conditions (diabetes, CRAO, ischemic CVO)

Implicit time: time from light flash to peak of b-wave; measured in milliseconds

Increased in various hereditary conditions

Oscillatory potential: wavelets on ascending b-wave of scotopic and photopic bright flash ERG

Generated in middle retinal layers (inner plexiform layer): may be inhibitory potentials from amacrine cells

Reduced in conditions of retinal hypoxia or microvascular disease

c-wave: RPE; late (2–4 seconds) positive deflection; occurs in dark-adapted state

Early receptor potential (ERP) (Figure 11-11): outer segments of photoreceptors; completed within 1.5 ms

Represents bleaching of visual pigment; requires intense stimulus in dark-adapted state

Ganglion cells are not measured; therefore, flash ERG is not useful in glaucoma

Figure 11-10 The photopic (cone-mediated) ERG is a light-adapted, bright flash-evoked response from the cones of the retina; the rods do not respond in the light-adapted state.

(From Slamovits TL: Basic and Clinical Science Course: Section 12: Orbit, Eyelids, and Lacrimal System. San Francisco, American Academy of Ophthalmology, 1993.)

Figure 11-11 Normal human early receptor potential (ERP). This rapid response is complete within 1.5 ms and is believed to be generated by the outer segments. An intense, bright stimulus in the dark-adapted state is needed for an ERP to be obtained.

(Redrawn from Berson EL, Goldstein EG: Early receptor potential in dominantly inherited retinitis pigmentosa. Arch Ophthalmol 83:412–420, 1970. From Slamovits TL: Basic and Clinical Science Course: Section 12: Orbit, Eyelids, and Lacrimal System. San Francisco, American Academy of Ophthalmology, 1993.)

Photopic (light adapted)

measures cone function; light adapted to bleach out rods

Flicker ERG: flashing light at 30 flashes/second isolates cone response

Small wave follows each flash

Cone response because rods cannot recycle rhodopsin this quickly

Poor response at 30 cycles/second indicates abnormal cone function; rods can respond up to 20 Hz

Cones also respond to repetitive light

Scotopic (dark adapted)

measures rod function; dark adapted for 30 min (Figure 11-12)

Dim white or blue flash below cone threshold

At low intensity: small a- and b-waves

At increasing intensity: implicit time shortens, b-wave amplitude increases

Bright-flash ERG (in scotopic state; measures combined maximal rod and cone response): deep a-wave and large b-wave; oscillatory potentials are present (Figure 11-13)

Figure 11-12 The scotopic (rod-mediated) ERG is a dark-adapted, dim flash (below cone threshold)-evoked response that records the signal from the rods. The test should be performed after at least 30 minutes of dark adaptation.

(From Slamovits TL: Basic and Clinical Science Course: Section 12: Orbit, Eyelids, and Lacrimal System. San Francisco, American Academy of Ophthalmology, 1993. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Figure 11-13 The bright flash, dark-adapted ERG stimulates both the cone and rod systems and gives large a and b-waves, with oscillatory potentials in the ascending b-wave. Some testing centers call this a ‘scotopic ERG,’ but the rods are not isolated by this method.

Indications

Diagnose generalized retinal degeneration

Assess family members for heritable retinal degeneration

Assess decreased vision and nystagmus present at birth

Assess retinal function in presence of opaque ocular media or vascular occlusion

Evaluate functional visual loss

Disease states (Figure 11-14, Table 11-2)

CRAO: normal a-wave (perfused by choroid), absent b-wave

Ischemic CVO: reduced b-wave amplitude, reduced b : a-wave ratio, prolonged b-wave implicit time

Retinitis pigmentosa: early, reduced amplitude (usually b-wave) and prolonged implicit time; later, extinguished with no rod or cone response to bright flash

Female carriers of X-linked RP: prolonged photopic b-wave implicit time, reduced scotopic b-wave amplitude

Sector RP: normal b-wave implicit time

Cone dystrophy: abnormal photopic and flicker, normal scotopic

X-linked foveal retinoschisis: normal a-wave until late, reduced b-wave (especially scotopic)

Retinal detachment: reduction in amplitude corresponds to extent of neurosensory loss (50% decrease in amplitude = 50% of neurosensory retina is functionally detached)

Diffuse progressive retinal disease: increased b-wave implicit time

Nonprogressive retinal disease: decreased b-wave amplitude

MEWDS: reduced a-wave

Chalcosis: reduced amplitude (suppressed by intraocular copper ions)

Retinal microvascular disease (diabetes, hypertension, CVO): loss of oscillatory potentials

Achromotopsia: absent cone function; normal rod function

Leber’s congenital amaurosis: flat ERG

CSNB: normal a-wave, poor b-wave

Congenital rubella: normal ERG

Glaucoma: normal ERG

Optic neuropathy / atrophy: normal ERG

Figure 11-14 Electroretinogram patterns.

(From Slamovits TL: Basic and Clinical Science Course: Section 12: Orbit, Eyelids, and Lacrimal System. San Francisco, American Academy of Ophthalmology, 1993.)

Table 11-2 ERG patterns for various ocular diseases

Extinguished ERG abnormal photopic, normal ERG	Normal a-wave, reduced b-wave	Abnormal photopic, normal scotopic ERG
RP	CSNB; Oguchi’s disease	Achromotopsia
Ophthalmic artery occlusion	X-linked juvenile retinoschisis	Cone dystrophy
DUSN	CVO
Metallosis	CRAO
RD	Myotonic dystrophy
Drug toxicity (phenothiazine; chloroquine)	Quinine toxicity
Cancer-associated retinopathy

Pattern ERG (PERG)

Normal response is composed of 3 waves:

N₃₅: cornea-negative wave at 35 ms

P₅₀: cornea-positive wave peak at 50 ms

N₉₅: negative trough at 95 ms

Figure 11-15 Pattern ERG with components labeled. This waveform measures retinal ganglion cell function and is not related to the flash ERG test.

(After Treat GL: The pattern electroretinogram in glaucoma and ocular hypertension. In: Heckenlively JR, Arden GB (eds) Principles and Practice of Clinical Electrophysiology of Vision. St Louis, Mosby-Yearbook, 1991.)

Electro-oculogram (EOG)

Indirect measure of standing potential of eye (voltage difference between inner and outer retina) (Figure 11-16)

Figure 11-16 Diagram illustrating technique used in recording the electro-oculogram test; the patient is positioned so that the eyes will traverse a 30° arc between 2 blinking red lights. The skin electrodes are positioned at the lateral and inner canthi. The standing potential is measured as the patient moves his eyes between the lights, first in the dark and then in the light. The maximum amplitude from the light condition is compared with minimum value from the dark to give a light peak-to-dark trough ratio.

(From Heckenlively JR: Retinitis Pigmentosa. Philadelphia, JB Lippincott, 1988.)

Depolarization of basal portion of RPE produces light peak; normal result requires that both RPE and sensory retina be normal

Arden ratio

ratio of light-to-dark peak (2 : 1 is normal; <1.65 is abnormal); decreased ratio is due to photoreceptor or RPE disorder

Retinal Imaging

Optical Coherence Tomography (OCT)

Creates cross-sectional image of tissue using light

Provides retinal thickness measurements and cross-sectional retinal imaging to ∼5–10 µm depending on light source; anterior segment spectral domain OCT is useful to image anterior segment, in particular the cornea and angle

Superluminescent diode fires beam of infrared light through fiberoptic Michelson interferometer at both the eye and a reference mirror; the reflected light from the retina is compared with the light from the reference mirror and analyzed so that the tissue reflectivity (similar to ultrasound) and density can be determined. With time-domain OCT (TDOCT), the reference mirror moves; with spectral-domain OCT (SDOCT) the mirror does not move and a Fourier transform is used to obtain imaging information (this makes SDOCT much faster than TDOCT)

Useful for optic nerve (glaucoma) and macular pathology (edema, hole, pucker); can compare thickness in cases of macular edema from one visit to next; can diagnose and differentiate vitreomacular pathology e.g. stage 1 macular hole vs full-thickness hole (≥stage 2) vs pseudohole or lamellar holes (Figures 11-17, 11-18)

Figure 11-17 Optical coherence tomography principle.

(Adapted from Shuman JS, Hee MR, Puliafito CA et al: Quantification of nerve fiber layer thickness in normal and glaucomatous eyes using optical coherence tomography. Arch Ophthalmol 113:586-596, 1995. From: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Figure 11-18 Stage 2 macular hole. A, fundus photograph, B, OCT.

(From: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Heidelberg Retinal Tomograph (HRT)

Laser tomography

Confocal scanning laser produces 3-dimensional sections of optic nerve and retina through undilated pupil

670 nm diode laser that is periodically deflected by oscillating mirrors; laser scans retina, and instrument measures reflectance and constructs series of 2-dimensional images at different depths, which are combined to create a multilayer 3D topographic image

Measures surface height to within 20 µm

Retinal Thickness Analyzer (RTA)

Creates thickness contour map

HeNe laser scans central 2 × 2 mm area; receives 2 reflections, 1 from ILM and 1 from RPE, then maps distance between these layers

Scanning Laser Ophthalmoscope (SLO)

Modulated red light laser (633 nm)

Performs funduscopy and automated perimetry simultaneously

Ultrasound

Acoustic imaging of globe and orbit

A-scan

1-dimensional display (amplitude of echoes plotted as vertical height against distance) (Figures 11-19 to 11-21)

Figure 11-19 A-scan ultrasound demonstrating high internal reflectivity.

(From Friedman NJ, Kaiser PK, Pineda R II: The Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology. 3rd ed. Philadelphia, Elsevier, 2009.)

Figure 11-20 A-scan ultrasound demonstrating medium internal reflectivity.

(From Friedman NJ, Kaiser PK, Pineda R II: The Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology. 3rd ed. Philadelphia, Elsevier, 2009.)

Figure 11-21 A-scan ultrasound demonstrating low internal reflectivity.

(From Friedman NJ, Kaiser PK, Pineda R II: The Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology. 3rd ed. Philadelphia, Elsevier, 2009.)

B-scan

2-dimensional display (amplitude of echoes represented by brightness on a grey scale image) (Figure 11-22)

Figure 11-22 B-scan ultrasound demonstrating choroidal detachment.

(From Kaiser PK, Friedman NJ, Pineda R II: Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology, 2nd edn. Philadelphia, Saunders, 2004.)

Reflectivity

height of spike on A-scan and signal brightness on B-scan

Internal reflectivity refers to amplitude of echoes within a lesion or tissue

Internal structure

degree of variation in histologic architecture within a mass lesion

Regular internal structure indicates homogenous architecture (minimal or no variation in the heights of spikes in A-scan and uniform appearance of echoes on B-scan)

Sound attenuation

occurs when acoustic wave is scattered, reflected, or absorbed by tissue

Decrease in strength of echoes within or posterior to lesion; may produce a void posterior to lesion called ‘shadowing’ (caused by dense substances [bone, calcium, foreign body])

After movement

dynamic features of lesion echoes

Observe B-scan echoes for motion after cessation of eye movements (i.e. rapid movement of vitreous hemorrhage distinguished from slower, undulating movement of rhegmatogenous retinal detachment)

Vascularity

spontaneous motion of echoes within lesion corresponds to blood flow; may be visualized with Color doppler

Specific lesions

(Tables 11-3 and 11-4) (Figures 11-22 to 11-27)

Asteroid hyalosis:

A-SCAN: medium to high internal reflectivity

B-SCAN: bright echoes in vitreous due to calcium soaps; area of clear vitreous usually present between opacities and posterior hyaloid face

Intraocular foreign body:

B-SCAN: high reflectivity when ultrasound probe is perpendicular to reflective surface of foreign body; bright echo persists when gain turned down; shadowing often present

Intraocular calcification:

A-SCAN: high amplitude peak due to strong acoustic interface

B-SCAN: white echoes; partial or complete shadowing

DDx: tumors (retinoblastoma, choroidal osteoma, optic nerve meningioma, choroidal hemangioma, choroidal melanoma), Toxocara granuloma, chronic retinal detachment, optic nerve head drusen, vascular occlusive disease of optic nerve, phthisis bulbi, intumescent cataractous lens

Table 11-3 Ultrasound characteristics of various lesions

Table 11-4 Ultrasound characteristics of different types of detachments

Figure 11-23 B-scan ultrasound demonstrating serous retinal detachment with shifting fluid, shallow peripheral choroidal detachment, and diffuse scleral thickening.

(From Kaiser PK, Friedman NJ, Pineda R II: Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology, 2nd edn. Philadelphia, Saunders, 2004.)

Figure 11-24 B-scan ultrasound demonstrating scleral thickening and the characteristic peripapillary T sign.

(From Kaiser PK, Friedman NJ, Pineda R II: Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology, 2nd edn. Philadelphia, Saunders, 2004.)

Figure 11-25 B-scan ultrasound demonstrating elevated mass with underlying thickened choroid.

(From Kaiser PK, Friedman NJ, Pineda R II: Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology, 2nd edn. Philadelphia, Saunders, 2004.)

Figure 11-26 B-scan ultrasound demonstrating dome-shaped choroidal mass.

(From Kaiser PK, Friedman NJ, Pineda R II: Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology, 2nd edn. Philadelphia, Saunders, 2004.)

Figure 11-27 B-scan ultrasound of a patient with choroidal metastasis demonstrating elevated choroidal mass with irregular surface and overlying serous retinal detachment.

(From Kaiser PK, Friedman NJ, Pineda R II: Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology, 2nd edn. Philadelphia, Saunders, 2004.)