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.)

Fluorescein Angiogram (FA)

Phases

choroidal filling, arterial, venous, recirculation

Sodium fluorescein in a hydrocarbon based yellow-red dye with a molecular weight of 376 daltons (Da). Dye enters choroidal circulation via short posterior ciliary arteries 10-15 seconds after injection; choroidal flow is very rapid; choriocapillaris filling is usually completed in the AV or early venous phase; cilioretinal artery is filled at time of choroidal filling; central retinal artery takes more circuitous route, resulting in dye arriving 1–2 seconds after choroidal filling; AV phase occurs 1–2 seconds after arterial phase; veins fill in 10–12 seconds (Figures 11-28 to 11-32)

Exciter filter emits blue light that stimulates fluorescein to emit yellow-green light (barrier filter transmits only green light) so two filters are required to image: fluorescein absorbs light at 465–490 nm (blue), emits at 520–530 nm (green)

80% bound to albumin and other serum proteins

90% excreted from kidney (also liver) within 24–36 hours

Transient yellowing of skin and conjunctiva that lasts 8–12 hours; most common adverse events: nausea (3–15%), vomiting (5%), pruritus (5%); anaphylactic reaction in 1 : 100,000; death occurs in 1 : 220,000; pregnancy in first trimester is a relative contraindication

Figure 11-28 FA demonstrating choroidal and early arterial filling.

Figure 11-29 FA demonstrating arterial phase.

Figure 11-30 FA demonstrating early venous phase with laminar filling.

Figure 11-31 FA demonstrating peak AV transit.

Figure 11-32 FA demonstrating late phase.

Characteristics

Hyperfluorescence: leakage (fenestrated choriocapillaris, iris vessels), staining (structures such as collagen), pooling (pockets of fluid), window defects (RPE defects)

Hypofluorescence: blockage (opacity that reduces fluorescence; e.g. RPE, blood, xanthophyll) or filling defect (ischemia)

Macular dark spot is due to blockage by xanthophyll in outer plexiform layer and tall RPE cells with increased melanin and lipofuscin

Fluorescein passes through Bruch’s membrane, cannot pass through RPE or retinal capillaries

Autofluorescence: fluorescence prior to fluorescein dye injection; seen in optic nerve drusen, astrocytic hamartomas, and large deposits of lipofuscin

Choroidal filling: choroidal lesions (malignant melanoma, cavernous hemangioma) and cilioretinal artery

Arterial phase filling: retinal lesions (capillary hemangioma, NVD)

Indocyanine Green (ICG)

Sterile, water-soluble, tricarbocyanine dye with a molecular weight of 775 Da. Absorbs light at 805 nm, emits at 835 nm (near infrared), which penetrates RPE, blood, and other ocular pigments to greater extent than visible light and fluorescein

98% bound to serum proteins (80% to globulins); therefore, leaks very slowly from choroidal circulation allowing enhanced imaging of the choroidal circulation; CNV often appears as hot spot (bright area; occurs within 3–5 min, lasts 20 min) (Figure 11-33)

Figure 11-33 Serous retinal pigment epithelial detachment seen on FA: A, with associated hot spot seen on ICG (B).

(From Reichel E: Indocyanine green angiography. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Excreted via liver into bile

Safer than fluorescein angiography; nausea and vomiting uncommon; should not be done in patients allergic to iodide, uremic, or with liver disease

Disorders

Vitreous Abnormalities

Asteroid Hyalosis

Refractile particles (calcium soaps) suspended in vitreous

More common in older patients and those with diabetes; 25% bilateral

Rarely affects vision, but may prevent visualization of posterior pole, use FA to look for abnormalities in these patients

Pathology

gray spheres with ‘Maltese cross’ birefringence on polarization

Synchisis Scintillans (Cholesterol Bulbi)

Cholesterol crystals derived from old vitreous hemorrhage; with PVD crystals settle inferiorly

Rare, unilateral

Occurs after blunt or penetrating trauma in blind eyes

Crystals sink to bottom of globe because no fixed vitreous framework

Primary Amyloidosis

Vitreous involvement in familial amyloidotic polyneuropathies (FAP I and II get systemic manifestations)

Amyloid enters via retinal vessels

Patients have cardiac disease and amyloid neuropathy

Posterior Vitreous Detachment (PVD)

Separation of posterior hyaloid face from retina

Mechanism

vitreous syneresis (liquefaction) and contraction with age

Symptoms

floaters; may see flashes (due to traction on retina)

Findings

acute symptomatic PVD may have retinal tear (10–15% of acute symptomatic PVDs), vitreous hemorrhage (hemorrhagic PVD; 7.5% of PVDs) if vessel is torn during vitreous separation (70% risk of retinal tear), retinal detachment (RD) especially when pigmented vitreous cell is present

Vitreous Hemorrhage (VH)

Etiology

diabetes (most common), other proliferative retinopathies, trauma, PVD, Terson’s syndrome (blood from subarachnoid hemorrhage travels along optic nerve and into eye), ruptured retinal arterial macroaneurysm, retinal angioma; in children, consider child abuse, pars planitis, X-linked retinoschisis

Ochre membrane

results from chronic hemorrhage accumulating on posterior surface of detached vitreous

Persistent Hyperplastic Primary Vitreous (PHPV)

(See Ch. 5, Pediatrics / Strabismus.)

Retinal Abnormalities

Congenital

(See Ch. 5, Pediatrics / Strabismus.)

Trauma

Commotio Retinae (Berlin’s Edema)

Transient retinal whitening at level of deep sensory retina due to disruption (probably photoreceptor outer segments) with photoreceptor loss and thinning of outer nuclear and plexiform layers; not true edema

Pigmentary changes can occur (RPE hyperplasia); traumatic macular hole may develop; usually resolves without sequelae (Figure 11-34)

Figure 11-34 Berlin’s edema (commotio retinae) in a patient after blunt ocular trauma.

(From Rubsamen PE: Posterior segment ocular trauma. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Contusion of RPE

Blunt trauma can cause RPE edema with overlying serous RD

Choroidal Rupture

Tear in choroid, Bruch’s membrane, and RPE due to blunt or penetrating trauma

Mechanism

mechanical deformation results in rupture of choroid; sclera is resistant due to high tensile strength, retina is resistant due to elasticity; Bruch’s membrane is less elastic and breaks with choroid and RPE

Direct

occurs anteriorly at site of impact; oriented parallel to ora serrata

Indirect

occurs posteriorly away from site of impact; usually crescent-shaped, concentric with and temporal to optic disc; often associated with VH

Findings

choroidal neovascular membrane (CNV) can develop during healing process (months to years after trauma; can regress spontaneously), scar forms by 3–4 weeks, hyperplasia of RPE at margin of lesion (Figure 11-35)

Figure 11-35 Choroidal rupture after blunt trauma.

(From Rubsamen PE: Posterior segment ocular trauma. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Retina Sclopetaria

Trauma to retina and choroid caused by transmitted shock waves and necrosis from high-velocity projectile

Findings

rupture of choroid and retina with hemorrhage and commotio; vitreous hemorrhage can occur; lesion heals with white fibrous scar and RPE changes (Figure 11-36)

Figure 11-36 Gunshot wound to the periocular region demonstrating appearance of retina sclopetaria: A, acute; B, chronic.

(From Rubsamen PE: Posterior segment ocular trauma. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Low risk of RD in young patients with formed vitreous; posterior vitreous face usually intact; choroid and retina tightly adherent

Traumatic Retinal Tear

Most patients are young with formed vitreous that tamponades the tear

As vitreous liquefies over time, fluid passes through breaks, causing retina to detach

Trauma is associated with 10–20% of all phakic RDs

Treatment

laser therapy or cryotherapy for horseshoe tear, operculated tear, and retinal dialysis without RD; vitrectomy with gas for macular hole; scleral buckle for RD due to retinal tear; proliferative vitreoretinopathy (PVR) is uncommon

Purtscher’s Retinopathy

Due to head trauma or compressive injury to trunk

Unilateral or bilateral

Findings

retinal whitening, hemorrhages, cotton wool spots, papillitis; may have positive RAPD (Figure 11-37)

Figure 11-37 Purtscher’s retinopathy.

(From Regillo CD: Distant trauma with posterior segment effects. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

DDx

pancreatitis, fat emboli, lupus, leukemia, amniotic fluid emboli, dermatomyositis

FA

leakage from retinal vasculature, late venous staining

May take up to 3 months to resolve

Terson’s Syndrome

Vitreous hemorrhage following subarachnoid or subdural hemorrhage due to intracranial hypertension blocking venous return from eye; patients have acute neck stiffness

20% of patients with spontaneous or traumatic subarachnoid hemorrhage will present with vitreous hemorrhage; bleeding can also occur between ILM and retina (Figure 11-38)

Figure 11-38 Terson’s syndrome.

(From Regillo CD: Distant trauma with posterior segment effects. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Valsalva Retinopathy

Rise in intrathoracic or intra-abdominal pressure against a closed glottis (Valsalva maneuver) causes superficial veins to rupture with hemorrhage under ILM

Preretinal hemorrhage in macula causes sudden decreased vision

Fat Emboli Syndrome

Follows fracture of medullated bones; occurs in 5% of patients with long-bone fractures

Affects multiple organ systems

Findings (in 50%)

cotton wool spots, small blot hemorrhages; rarely intravenous fat or CRAO

20% mortality

Whiplash Retinopathy

Associated with severe flexion / extension of head and neck without direct eye injury

Findings

mild reduction in vision (to 20/30); gray swelling of fovea, foveal pit (50–100 µm)

FA

may have tiny focal area of early hyperfluorescence

Macular Diseases

Epiretinal Membrane (Cellophane Maculopathy, Macular Pucker)

Proliferations at vitreoretinal junction, may contract and cause retinal folds and macular edema

12% prevalence in individuals 43–86 years old; 20% bilateral; 2% associated with retinal folds (decreased vision)

Associated with diabetes, retinal vascular occlusions, PVD, high myopia, retinal hole / tear, previous ocular or laser surgery, and increasing age

OCT

epiretinal membrane visible on surface of retina, distortion of retinal surface may be evident

Treatment

consider surgery for decreased vision (<20/50), marked retinal distortion, or metamorphopsia

Macular Hole

Due to tangential traction on foveal region by posterior cortical vitreous

Most commonly idiopathic (senile); may develop after trauma, surgery, CME, or inflammation

Female > male; bilateral in 25–30%; prevalence = 0.33%; average age of onset is 67 years; risk of developing in fellow eye <1% (no risk if PVD present)

Macular cyst may be precursor

Gass classification (Figure 11-39)

1 Premacular or impending hole with foveal detachment and macular cyst (yellow spot [1a] or ring [1b])

2 Full-thickness eccentric hole; usually <400 µm in width

3 Full-thickness hole with operculum, cuff of subretinal fluid, yellow deposits at base, positive Watzke-Allen sign

4 Full-thickness hole with PVD

Figure 11-39 Optical coherence tomography scans demonstrating cross-sectional image of all stages of macular hole formation and the full-thickness retinal defect characteristic of stage 3 and 4 holes.

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

Watzke-Allen sign

shine narrow-slit beam over macular hole, positive if patient perceives ‘break’ in slit beam

DDx

epiretinal membrane with pseudohole, lamellar hole, vitreomacular traction / detachment; for stage 1: drusen, CME, CSR

FA

window defect corresponding to the hole (hyperfluorescence during choroidal filling)

OCT

differentiates between various stages and other disease, hole always evident on scan; often have rim of SRF and cysts within edges of hole, occasionally operculum can be seen over the hole

Treatment

stage 1 may close spontaneously so observation; consider vitrectomy with peeling of posterior hyaloid and gas tamponade for stage 2 through stage 4; microplasmin enzyme recently found to close smaller MH in up to 40% of cases with intravitreal ocriplasmin (Thrombogenics) injection (experimental)

Complications of surgery

increased size of hole, RPE mottling, light toxicity, cataract, retinal tear, retinal detachment

Prognosis

good if recent onset and hole width < 400 µm, poor if >1 year duration

Traumatic macular hole

Rare (5%); due to disruption and necrosis of retinal photoreceptors with subsequent loss of retinal tissue; results from pre-existing commotio retinae in macula

Solar Retinopathy (Figure 11-40)

Photochemical retinal damage can occur after ∼90 seconds or longer of sungazing, thought to be caused by blue (441 nm) and near UV light (325–250 nm)

Figure 11-40 Solar retinopathy of both eyes.

(Courtesy of William E. Benson. From Baumal CR: Light toxicity and laser burns. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

With foveal fixation, retinal image of sun is 160 µm and is usually within the foveola and FAZ

Associated with solar eclipse, psychiatric disorders, religious rituals, or ingestion of hallucinogens

Symptoms

vision can range from normal to 20/100; usually returns to 20/20 to 20/40 within 6 months

Findings

yellow-white spot in fovea; later, red foveolar depression or lamellar hole

FA

intense staining of damaged RPE, particularly in acute phase of injury, but no leakage; as RPE heals, window defects develop (Figure 11-41)

Figure 11-41 Fluorescein angiography of solar retinopathy in the left eye.

(Courtesy of William E. Benson. From Baumal CR: Light toxicity and laser burns. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Central Serous Retinopathy / Chorioretinopathy (CSR) / Idiopathic Central Serous Choroidopathy (ICSC)

Serous retinal detachment ± retinal pigment epithelium detachment (PED) (Figure 11-42)

Figure 11-42 Idiopathic central serous retinopathy with large 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.)

Males (80%), typically in 4th–5th decade

Associated with hypertension, steroid use, psychiatric medication use, and type A personality

Findings

blurred vision, micropsia, paracentral scotoma; poor color vision; induced hyperopia, absent foveal reflex; after resolution, may have yellow subretinal deposits, RPE changes

DDx

AMD, VKH syndrome, uveal effusion syndrome, toxemia of pregnancy, optic nerve pit, pigment epithelial detachment from other causes (CNV)

FA

small focal hyperfluorescent dot (leakage of dye from choroid through RPE); later, dye accumulates beneath neurosensory detachment; ’smokestack’ appearance in 10%; expanding dot of hyperfluorescence in 80%, diffuse leakage in the rest (Figure 11-43)

Figure 11-43 Fluorescein angiogram demonstrating classic smokestack appearance.

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

OCT

sensory retinal elevation, may have PED (usually within or near subretinal fluid accumulation)

ICG

can be useful in helping to distinguish atypical diffuse CSR in older patients from occult CNV in exudative AMD and idiopathic polypoidal choroidal vasculopathy

Treatment

observation in most cases, consider laser to focal hot spots outside fovea or verteporfin (Visudyne) photodynamic therapy (PDT) for subfoveal spots or diffuse leakage (off label); rifampin and RU-486 have been used experimentally with limited success

Treatment indications:

1 Persistent serous detachment (>3 months)

2 Previous episode of CSR, with permanent vision reduction

3 Episode in fellow eye with vision loss

4 Demand for rapid recovery of binocular function for occupational reasons

Laser and PDT accelerate resolution of fluid, but does not result in better final vision or reduce rate of recurrence; laser may rarely cause CNV

Prognosis

90% spontaneous resorption in 1–6 months; 50% recur; 66% achieve 20/20; 14% with bilateral vision loss over 10 years

Age-Related Macular Degeneration (ARMD, AMD)

Leading cause of central visual loss in patients >60 years old in the United States and Western world

Risk factors

age, heredity, sex (female), race (white), smoking, nutrition, photic exposure, hypertension, light iris color, hyperopia

Symptoms

decreased vision, central scotoma, metamorphopsia

Forms

1 Nonexudative or dry (80–90%): drusen, pigment changes, RPE atrophy (Figures 11-44 to 11-47)

2 Exudative, neovascular, or wet (10-20%): characterized by CNV (Figures 11-48 to 11-50)

Figure 11-44 Nodular ‘hard’ drusen.

(From Edwards MG, Bressler NM, Raja SC: Age-related macular degeneration. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Figure 11-45 Dry, age-related macular degeneration demonstrating drusen and pigmentary changes (category 3).

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

Figure 11-46 Advanced, atrophic, nonexudative, age-related macular degeneration demonstrating subfoveal geographic atrophy (category 4).

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

Figure 11-47 Fluorescein angiogram of same patient as in Figure 11-46, demonstrating well-defined window defect corresponding to the area of geographic atrophy.

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

Figure 11-48 Exudative age-related macular degeneration, demonstrating subretinal hemorrhage from classic choroidal neovascular membrane.

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

Figure 11-49 Fluorescein angiogram of same patient as in Figure 11-48, demonstrating leakage from the CNV and blockage from the surrounding subretinal blood.

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

Figure 11-50 A-C, Neovascular, age-related macular degeneration.

(From Edwards MG, Bressler NM, Raja SC: Age-related macular degeneration. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Drusen

clinical marker for sick RPE; PAS-positive, mildly eosinophilic hyaline excrescences of abnormal basement membrane material between RPE basement membrane and inner Bruch’s membrane

Types of drusen

Hard (nodular / cuticular / hyaline): small yellow-white spots 50 µm in diameter

Soft: larger, less dense, more fluffy, with tapered edges; may resemble PED; associated with thickened inner Bruch’s membrane and wet AMD

Basal laminar: diffuse, confluent (blocks early, stains late on FA)

Calcific: sharply demarcated, glistening; associated with RPE atrophy

Drusen size classification

Small: <64 µm in diameter

Intermediate: 64–124 µm in diameter

Large: ≥125 µm in diameter (approximately equal to vein width at disk margin)

Also classified based on drusen extent:

Small drusen considered extensive if the cumulative area within 2 disc diameters of the center of the macula equal to at least that of the AREDS standard circle C-1 (with diameter

that of the average disc) – this corresponds to approximately 15 small drusen from stereo photographs or 5–10 small drusen

Intermediate drusen considered extensive if soft, indistinct drusen are present and the total area occupied by the drusen is equivalent to the area that would be occupied by 20 drusen each having a diameter of 100 µm. If no soft indistinct drusen are present, intermediate drusen are considered to be extensive when they occupy an area equivalent to at least

of a disc area (approximately 65, 100 µm diameter drusen)

DDx of yellow foveal spot

solar maculopathy, adult vitelliform dystrophy, Best’s disease, stage 1a macular hole, CSR, old subfoveal hemorrhage, CME, pattern dystrophy

FA

hyperfluorescence of drusen due to window defects (from degeneration of overlying RPE) and uptake of dye within drusen (staining)

Signs of CNV

subretinal blood, fluid, and / or lipid; RPE detachment (PED); gray-green subretinal discoloration

Types of CNV

historically defined by appearance of leakage on FA

Classic:

EARLY PHASE: bright, fairly uniform hyperfluorescence that progressively intensifies throughout the transit phase

LATE PHASE: progressive leakage of dye that extends beyond the margins of the CNV seen in early stages

Can also be defined by lesion location:

TYPE 1: CNV under RPE; PCV is a variant of type 1

TYPE 2: CNV above RPE

TYPE 3: retinal angiomatous proliferation (RAP) = often bilateral with small intraretinal hemorrhages and associated PED; develop retinal-choroidal anastamosis

Location of CNV

Extrafoveal: posterior border of CNV is 200–2500 µm from center of foveal avascular zone (FAZ)

Juxtafoveal: 1–199 µm from center of FAZ, or CNV 200–2500 µm from center of FAZ with blood or blocked fluorescence within 200 µm of FAZ center

Subfoveal: under center of FAZ

ICG

helpful for visualizing CNV that is not well seen on FA; CNV appears as focal hot spots or plaque of late hyperfluorescence; can demonstrate CNV under thin hemorrhage that would be blocked on FA; high-speed ICG useful to delineate feeder vessels of CNV

Treatment

follow Amsler grid, low-vision aids, vitamin supplements; consider intravitreal injections (anti-VEGF [vascular endothelial growth factor] agents), laser, or PDT for CNV

Supplements with high-dose antioxidants and zinc are helpful in reducing vision loss and the progression of disease in patients with category 3 and 4 AMD; ongoing AREDS2 study is evaluating lutein, zeaxanthin, and omega-3 fatty acids in addition to the original AREDS formulation

Avoid beta-carotene in smokers

Vitamin C and E can increase risk of myocardial infarction (MI) in postmenopausal women

Zinc is associated with benign prostate hypertrophy in men and stress incontinence in women

Macular Photocoagulation Study (MPS):

Treatment of well-demarcated extrafoveal or juxtafoveal CNV with uniform laser. After 5 years, 64% of untreated eyes had >6 lines of vision loss; 46% of treated eyes had >6 lines of vision loss; >50% recurrence rate. However, many patients do not qualify owing to subfoveal CNV and occult lesions

Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Trial:

Photodynamic therapy with verteporfin (Visudyne) can prevent vision loss in eyes with subfoveal, predominantly classic and occult AMD, with no classic CNV

Verteporfin in Photodynamic Therapy (VIP) Trial:

Photodynamic therapy with verteporfin (Visudyne) can prevent vision loss in eyes with occult and no classic CNV, especially if less than 4 MPS Da in size or baseline vision worse than 20/50

Pegaptanib (Macugen) VISION Trial: FDA-approved aptamer that is a selective VEGF antagonist binding to the 165 isoform of VEGF-A while sparing other isoforms; no longer commonly used; intravitreal injection every 6 weeks.

Ranibizumab (Lucentis) MARINA and ANCHOR Trials: FDA-approved, humanized, antigen-binding fragment (Fab) designed to bind and inhibit all VEGF isoforms; intravitreal injection monthly or as needed (CATT finding was equal efficacy when delivered monthly or as needed).

Bevacizumab (Avastin): Off-label, full-length antibody that binds and inhibits all VEGF isoforms (FDA approved for colorectal cancer): the Complications of Age Related Macular Degeneration treatment Trials (CATT) study reported that monthly avastin was non-inferior to monthly lucentis, but as needed avastin was not equal. There were significantly greater serious systemic adverse events in the avastin groups than lucentis; intravitreal injection monthly.

Aflibercept (VEGF Trap Eye) VIEW 1&2 Trials: fusion receptor decoy containing domain 2 from VEGF receptor 1 and domain 3 from VEGFR2 fused to human Fc fragment that blocks all isoforms of VEGF-A and placental growth factor (PLGF); injected every two months after a loading dose of 3 monthly injections.

Anti-VEGF safety: all anti-VEGF agents can get into the systemic circulation putting patients at risk of arteriothrombotic events (ATE) such as hypertension, MI, and stroke.

Combination treatment: Combination therapy with PDT and anti-VEGF agents has been shown to be safe with similar visual results and decreased injections (DENALI and MT BLANC studies). In particular, the best therapy for PCV is combination therapy PDT and anti-VEGF agents (EVEREST Study). In the future, combination therapy with radiation and other drugs will also likely be used.

Radiation: internal (strontium-90)(CABERNET Study) or external (low-dose X-ray radiation) combined with anti-VEGF agents (experimental)

Surgery: in certain cases, consider submacular surgery to remove CNV or displace hemorrhage in cases with large submacular hemorrhage, or macular translocation (experimental)

Prognosis

Rate of Progression to Advanced AMD (AREDS) over 5 years

1.3% many small or few medium drusen (if both eyes have many intermediate drusen, but no large drusen, then patient score = 1 in scale below)

18% many medium or any large drusen

43% unilateral advanced AMD

AREDS Clinical Severity Scale (AREDS) for AMD

Based on giving 1 point for the presence of ≥1 large drusen and / or pigment changes (hyper, hypo, or non-central GA) per eye, or 2 points for advanced AMD in 1 eye, then total 2 eyes to come up with a point score that shows patient’s risk of developing advanced AMD in 5 years:

Risk of CNV in fellow eye at 5 years: if drusen is present

Hard (nodular) = 10%

Soft = 30%

Pigmented = 30%

Soft and pigmented = 60%

Risk of fellow eye developing CNV: 4–12% per year; increased risk with multiple soft drusen, RPE clumping, densely packed drusen, PED

Major Age-Related Macular Degeneration Clinical Studies

Macular Photocoagulation Study (MPS)

Objective: to evaluate efficacy of laser photocoagulation in preventing visual loss from CNV

Methods: patients were randomly assigned to laser photocoagulation vs observation in the following groups:

Extrafoveal Study: well-demarcated CNV due to AMD or ocular histoplasmosis syndrome (OHS), or idiopathic, that was 200–2500 µm from center of foveal avascular zone (FAZ) with vision better than 20/100. Patients who received previous photocoagulation were excluded. Patients were randomly assigned to argon blue-green treatment to the entire CNV and 100–125 µm beyond the borders of the lesion vs observation

Juxtafoveal (Krypton) Study: well-demarcated CNV due to AMD or OHS, or idiopathic, that was 1–199 µm from center of foveal avascular zone (FAZ), or with a CNV more than 200 µm with blood or pigment extending within 200 µm and with vision better than 20/400. Patients were randomly assigned to Krypton red treatment of entire CNV and 100 µm beyond the borders of the lesion except on the foveal side of the lesion vs observation

Subfoveal, New CNV AMD Study: well-demarcated CNV due to AMD under the center of foveal avascular zone (FAZ) with vision between 20/40 and 20/320. The entire lesion had to measure less than 3.5 MPS disc areas in size and could be classic or occult CNV. Patients were randomly assigned to argon green or krypton red treatment of entire CNV and 100 µm beyond the borders of the lesion vs observation

Subfoveal Recurrent CNV Study: well-demarcated CNV due to AMD under the center of foveal avascular zone (FAZ) contiguous with previous laser treatment scar and with vision between 20/40 and 20/320. The entire lesion had to measure less than 6MPS disc areas in size and could be classic or occult CNV. Patients randomly assigned to argon green or krypton red treatment of entire CNV and 100 µm beyond the borders of the lesion vs observation

DEFINITIONS:

EXTRAFOVEAL: 200–2500 µm from center of foveal avascular zone (FAZ)

JUXTAFOVEAL: 1–199 µm from center of FAZ

SUBFOVEAL: extends beneath center of fovea

MAIN OUTCOME MEASURES: visual acuity, contrast sensitivity, reading speed, persistent and / or recurrent CNV, treatment complications

Results

Extrafoveal Study:

After 18 months:

AMD: 25% of treated vs 60% of untreated eyes had lost ≥6 lines of vision (a quadrupling of the visual angle [i.e. 20/50 to 20/200])

POHS: 9.4% of treated vs 34.2% of untreated eyes had lost ≥6 lines of vision

IDIOPATHIC: sample size (67) was too small to reach clinical significance, but trend was similar to results for AMD and POHS

Recurrence of CNV after argon laser was 52% with AMD, 28% with POHS, 28% with idiopathic CNV

After 3 years:

Relative risk of severe vision loss (≥6 lines) for no treatment vs treatment was 1.4 for AMD, 5.5 for POHS, and 2.3 for idiopathic CNV

After 5 years:

AMD: treated eyes lost 5.2 lines of vision vs 7.1 lines in untreated eyes; recurrence in 54% of treated eyes; 26% developed CNV in fellow eye

POHS: treated eyes lost 0.9 line of vision vs 4.4 lines in untreated eyes; recurrence in 26% of treated eyes

IDIOPATHIC: treated eyes lost 2.7 lines of vision vs 4.4 lines in untreated eyes; recurrence in 34% of treated eyes

Juxtafoveal Study:

After 3 years:

POHS: 4.6% of treated vs 24.6% of untreated eyes had lost ≥6 lines of vision

IDIOPATHIC: 10% of treated vs 37% of untreated eyes had lost ≥6 lines of vision

After 5 years:

Relative risk of severe vision loss (≥6 lines) for no treatment vs treatment was 1.2 for AMD (hypertensive patients had little or no benefit), 4.26 for POHS, and intermediate between AMD and POHS for idiopathic CNV

Subfoveal Recurrent AMD Study:

After 3 years: 12% of treated vs 36% of untreated eyes had lost ≥6 lines of vision

Conclusions

Treat extrafoveal CNV in patients with AMD, POHS, and idiopathic lesions

Patients with juxtafoveal CNV (AMD, POHS, and idiopathic) benefit from krypton laser photocoagulation, except for hypertensive AMD patients

AMD patients with subfoveal CNV (new or recurrent) benefit equally from argon green or krypton red laser treatment

For unilateral CNV, large drusen and focal hyperpigmentation are risk factors for development of CNV in fellow eye

Treatment of AMD patients with juxtafoveal CNV is beneficial when the lesion is classic, even though CNV recurs; treatment of classic CNV alone in lesions with both classic and occult CNV was not beneficial

Treatment of Age-Related Macular Degeneration with Photodynamic Therapy Trial (TAP)

Objective: to evaluate verteporfin (Visudyne) ocular photodynamic therapy (OPT) in the management of subfoveal CNV with some classic characteristics

Methods: patients with evidence of AMD, age >50 years, evidence of new or recurrent subfoveal ‘classic’ (can have occult features) CNV by fluorescein angiography with greatest linear dimension of CNV <5400 µm (9MPS disc areas), ETDRS visual acuity of 20/40 to 20/200, and the ability to return every 3 months for 2 years. Patients were excluded who had other ocular diseases that could compromise visual acuity, history of previous experimental treatment for CNV, porphyrin allergy, liver problems, or intraocular surgery within the previous 2 months. Two thirds of patients in both studies were randomly assigned (2:1 randomization scheme) to receive verteporfin (Visudyne 6 mg/m²) and one third to control vehicle (D₅W IV infusion) infused over a 10-minute period. All patients were then irradiated with the use of a 689-nm diode laser (light dose: 50 J/cm²; power density: 600 mW/cm²; duration: 83 seconds) 15 minutes after the start of the infusion

Results: enrollment included 609 patients (311 in Study A and 298 in Study B). Vision was stabilized or improved in 61.4% of patients treated with Visudyne OPT compared with 45.9% treated with placebo at 12 months. The difference was sustained at 24 and 60 (TAP Extension Study) months. In subgroup analysis, the visual acuity benefit was most pronounced for lesions in which the area of classic CNV occupied more than 50% of the entire area of the lesion (predominantly classic). Specifically, 33% of the Visudyne-treated eyes compared with 61% of the placebo-treated eyes sustained moderate visual loss. No difference in visual acuity was noted when the area of classic CNV was greater than 0% but less than 50% of the entire lesion (minimally classic). Sixteen percent of patients experienced an improvement in vision (1 or more lines) in the Visudyne-treated group compared with 7.2% in the control group. Overall, the Visudyne group was 34% more likely to retain vision. Most patients required periodic retreatments with an average of 3.4 (of a possible 4) being required in the first year, 2.1 in the second year (5.5 total over 24 months), and 1.5 in the third year (7 total over 36 months)

Conclusions: Visudyne ocular photodynamic therapy is recommended for subfoveal, predominantly classic, CNV

Verteporfin in Photodynamic Therapy (VIP) Trial Verteporfin in Photodynamic Therapy–Pathologic Myopia (VIP-PM) Trial

Objective: to evaluate Visudyne ocular photodynamic therapy (OPT) in the management of subfoveal CNV not included in the original TAP investigation

Methods: patients with evidence of AMD, age >50 years, evidence of subfoveal ‘occult’ only CNV by FA with recent disease progression defined as evidence of hemorrhage, loss of ≥1 line of vision, or increased size of the lesion by 10% during the preceding 3 months, and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity ≥20/100; or subfoveal ‘classic’ CNV with ETDRS visual acuity of ≥20/40, greatest linear dimension of CNV <5400 µm (9 MPS disc areas), and the ability to return every 3 months for 2 years. Patients were excluded who had other ocular diseases that could compromise visual acuity, history of previous experimental treatment for CNV, porphyrin allergy, liver problems, or intraocular surgery within the previous 2 months. Two-thirds of the patients in both studies were randomly assigned (2 : 1 randomization scheme) to receive verteporfin (Visudyne 6 mg/m²) and one third to control vehicle (D₅W IV infusion) infused over a 10-minute period. All patients were then irradiated with the use of a 689 nm diode laser (light dose: 50 J/cm²; power density: 600 mW/cm²; duration: 83 seconds) 15 minutes after the start of the infusion

Results: 459 patients enrolled. The 1-year results showed no statistically significant difference between the Visudyne-treated patients and placebo (difference 4.2%). However, by 24 months, a statistically significant difference was seen that was due to a decline in vision in the control group (difference 13.7%). Moreover, this difference was most pronounced in patients with ‘occult’ only CNV lesions measuring <4MPS disk areas in size at baseline, or who had a baseline visual acuity of 20/50 or worse

Few ocular or other systemic adverse events were seen with Visudyne therapy. In 4.4% of patients, an immediate severe visual decrease within 7 days of treatment was observed

Conclusions: Visudyne ocular photodynamic therapy (OPT) is recommended in the management of subfoveal occult but not classic CNV when there is evidence of recent disease progression, especially if the baseline lesion size is smaller than 4 MPS DA, or the baseline vision is worse than 20/50

Age-Related Eye Disease Study (AREDS)

Objective: to evaluate the effect of high-dose supplements on the progression of AMD, and on the development and progression of cataracts

Methods: patients aged 55–80 years with 20/32 or better vision OU, or 20/32 or better in one eye and AMD in fellow eye, received antioxidants (vitamin C [500 mg], vitamin E [400 IU], beta-carotene [vitamin A, 15 mg]), zinc (80 mg plus 2 mg copper), both, or placebo

Categorized into 4 groups:

Category 1: fewer than 5 small (<63 µm) drusen

Category 2 (mild AMD): multiple small drusen or single or nonextensive intermediate (63–124 µm) drusen, or pigment abnormalities

Category 3 (intermediate AMD): extensive intermediate-sized drusen, or 1 or more large (>125 µm) drusen, or noncentral geographic atrophy

Category 4 (advanced AMD): vision loss (<20/32) due to AMD in 1 eye (due to either central / subfoveal geographic atrophy or exudative macular degeneration

Primary outcomes:

Progression to advanced AMD: treatment for CNV or photographic evidence (geographic atrophy of center of macula, nondrusenoid RPE detachment, serous or hemorrhagic RD, subretinal hemorrhage or fibrosis)

Moderate vision loss: ≥15-letter loss (doubling of visual angle)

Development and progression of lens opacities

Results: 4757 patients enrolled

Antioxidants plus zinc: reduced the risk of progression to advanced AMD and vision loss over 6 years in 25% of high-risk patients

HIGH-RISK PATIENTS: intermediate AMD (many intermediate drusen [63–124 µm] or 1 large drusen [≥125 µm] in 1 or both eyes) or advanced AMD (in 1 eye only)

Zinc alone: reduced risk of vision loss by 21%

Antioxidants alone: reduced risk of vision loss by 17%

Conclusions

High-dose supplements are beneficial in reducing the risk of vision loss in patients with high-risk AMD (categories 3 and 4). Caution should be exercised in smokers or recent smokers in the use of high-dose beta-carotene because of the possible increased risk of lung cancer

Treatment is of no benefit in patients with no AMD or early AMD (several small or intermediate drusen)

Treatment does not affect development or progression of cataract

Age-Related Eye Disease Study (AREDS2)

Objective: to evaluate the effect of high-dose supplements, macular carotenoids, and omega-3-fatty acid on the progression of AMD

Methods: patients randomized to receive various combinations of vitamin C (500 mg), vitamin E (400 IU), beta-carotene (vitamin A, 15 mg), zinc (80 mg plus 2 mg copper), lutein (10 mg), zeaxanthin (2 mg), omega-3 long-chain polyunsaturated fatty acids (LCPUFA) in the form of docosahexaenoic acid (DHA) (350 mg) and eicosapentaenoic acid (EPA) (650 mg)

VEGF Inhibition Study in Ocular Neovascularization trial (VISION)

Objective: to evaluate intravitreal pegaptanib for subfoveal CNV due to neovascular AMD

Methods: 2 concurrent randomized, double-masked clinical trials, 1208 patients received either pegaptanib intravitreal injection (0.3 mg, 1.0 mg, or 3.0 mg) or a sham injection into study eye every 6 weeks for a total of 48 weeks. Patients were eligible for the trial if they were 50 years old or older and had subfoveal classic, minimally classic, and / or occult CNV due to wet AMD with a best-corrected visual acuity of 20/40 to 20/320 in the study eye.

Results: on average, patients treated with pegaptanib 0.3 mg and sham-treated patients continued to experience vision loss. However, the rate of visual acuity decline in the pegaptanib-treated group was slower than the rate in the patients who received sham treatment; 70% of patients treated with pegaptanib sodium injection (0.3 mg; n = 294) lost fewer than 15 letters of visual acuity compared with 55% in the control group (n = 296; P < 0.001); 10% of patients treated with pegaptanib sodium injection (0.3 mg; n = 294) had severe visual acuity loss (30 letters or more) compared with 22% in the control group (n = 296; P < 0.001). The beneficial effect was observed for all subtypes of neovascularization (NV). The beneficial effect was sustained for up to 2 years of follow-up

Conclusions: pegaptanib was better than sham and PDT for neovascular AMD

Minimally Classic / Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) Trial

Objective: pivotal phase III, multicenter, double- blind 24-month study, which compared monthly intravitreal injections of ranibizumab 0.3 or 0.5 mg or sham injections (n = 716) in patients with subfoveal occult only or minimally classic CNV due to wet AMD

Results: enrolled 716 patients with minimally classic and occult subfoveal CNV associated with AMD. The primary outcome was prevention of moderate visual loss (≤15 letters loss of vision), which was seen in 94.5% with ranibizumab 0.3 mg, 94.6% with ranibizumab 0.5 mg and 62.2% of patients receiving sham injections (P < 0.001). Vision improved by ≥15 letters for a significantly (P < 0.0001) greater number of ranibizumab-treated patients (24.8% for 0.3 mg and 33.8% for 0.5 mg) versus sham-treated patients (5.0%). Mean increases in VA from baseline were +6.5 letters for the ranibizumab 0.3 mg group and +7.2 letters for the ranibizumab 0.5 mg group, whereas sham-injected patients had a mean decrease of −10.4 letters. This benefit in VA in ranibizumab-treated patients was maintained through 24 months. At 24 months, 90% of ranibizumab-treated patients in the MARINA study lost less than 15 letters of visual acuity; 33% gained 15 or more letters of visual acuity (P < 0.01). Ranibizumab-treated patients exhibited a statistically significant improvement compared with sham-treated patients in all subgroups for all outcome measures.

Conclusions: ranibizumab was better than sham for occult with no classic and minimally classic CNV due to neovascular AMD

Anti-vascular endothelial growth factor (VEGF) Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization (CNV) in Age-related Macular Degeneration (ANCHOR) Trial

Objective: second pivotal phase III, multicenter, randomized, double-masked 24-month clinical trial, which compared ranibizumab with the active control verteporfin PDT in subfoveal predominantly classic CNV due to wet AMD

Results: enrolled 423 patients with predominantly classic subfoveal CNV associated with AMD. The primary outcome was prevention of moderate visual loss (≤15 letters loss of vision), which was seen in 94.3% with ranibizumab 0.3 mg, 96.4% with ranibizumab 0.5 mg and 64.3% of patients receiving PDT (P < 0.001). Vision improved by ≥15 letters in significantly more ranibizumab-treated patients (35.7% for 0.3 mg and 40.3% for 0.5 mg) than PDT-treated patients (5.6%; P < 0.0001). At 12 months, mean change in VA increased by +8.5 letters in the ranibizumab 0.3 mg group and by +11.3 letters in the 0.5 mg group, but decreased by −9.5 letters in the sham group (P < 0.0001)

Conclusions: ranibizumab was superior to verteporfin for treatment of predominantly classic CNV due to neovascular AMD

Other Disorders Associated with Choroidal Neovascular Membrane (CNV)

Treatment for all CNV

consider laser only for extrafoveal lesions (MPS showed that laser treatment for juxtafoveal and extrafoveal CNV was beneficial); juxtafoveal and subfoveal lesions are treated with anti-VEGF agents or photodynamic therapy (see above)

Presumed Ocular Histoplasmosis Syndrome (POHS)

Due to Histoplasma capsulatum, a dimorphic fungus (mold in soil, yeast in animals and birds) endemic to Mississippi and Ohio River valleys; rare in Europe; rare among African Americans. Age of onset commonly 20–45 years; no sex predilection; 90% of patients with ocular signs have positive skin reaction (>5 mm) to intracutaneous 1 : 100 histoplasmin (test usually not used because it may incite macular disease)

Macular involvement associated with HLA-B7, HLA-DRw2; however, HLA typing is not commonly used

Primary infection involves inhalation of spores into respiratory tract and a self-limited flu-like illness; dissemination of the fungus then occurs to spleen, liver, and choroid. Primary choroidal infection causes granulomatous, clinically unapparent inflammation that resolves into a small, atrophic scar (‘histo spot’) that can disrupt Bruch’s membrane

Findings

POHS consists of the triad of peripapillary atrophy, multiple punched-out chorioretinal scars (‘histo spots,’ may enlarge, 5–10% develop new spots), and maculopathy. No anterior or posterior segment cell; CNV can occur (different from that in AMD in that vessels penetrate Bruch’s membrane and extend over RPE; a second layer of RPE forms [basal side up] and attempts to encircle the CNV) (Figure 11-51)

Figure 11-51 POHS demonstrating peripapillary scarring and macular, juxtafoveal choroidal neovascular membrane with surrounding subretinal hemorrhage.

(From Noorthy RS, Fountain JS: Fungal uveitis. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Risk of CNV

1% with normal disc and macula; 25% risk over 4 years if not normal

CXR

calcifications

Angioid Streaks

Peripapillary linear cracks in thickened, degenerated, and calcified Bruch’s membrane (Figure 11-52)

Figure 11-52 Peripapillary angioid streaks.

(From Vander JF: Angioid streaks. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Subretinal hemorrhage can occur with minor trauma; patients should consider safety glasses

Etiology

50% associated with systemic condition, 50% idiopathic

Mnemonic PEPSI:

Pseudoxanthoma elasticum (PXE) (AR >> AD): female > male; peau d’orange appearance to retina; redundant skin with waxy, yellow, papule-like lesions (‘plucked chicken’ skin); increased elastic tissue; vascular malformations; abnormal mucosal vasculature may cause GI bleeds; may have optic nerve head drusen; angioid streaks present in 85%

Ehlers-Danlos syndrome (fibrodysplasia hyperelastica) (AD): hyperextensible skin due to deficient collagen matrix; other eye findings include subluxed lens, high myopia, keratoconus, blue sclera, retinal detachment

Paget’s disease: increased bone production and destruction; increased serum alkaline phosphatase; prone to basal skull and long bone fractures; othcr bone disorders (acromegaly, calcinosis)

Sickle cell: risk for autoinfarction of spleen and thrombotic episodes; other hematologic diseases (thalassemia, hereditary spherocytosis, acanthocytosis [Bassen-Kornzweig syndrome]); angioid streaks present in 1%

Idiopathic: 50%

DDx

lacquer cracks in myopia

Pathologic Myopia

High myopia = Axial length >26 mm; > −6 D of myopia;

Pathologic myopia = Axial length >32.5 mm; > −8 D of myopia;

Approximately 2% of US population; female > male

CNV due to PM commonly occurs in young patients; bilateral common (12–40%)

Findings

long, oval disc, may be tilted, cup usually shallow; temporal crescent; posterior staphyloma; tigroid fundus with visible choroidal vessels; lacquer cracks (breaks in Bruch’s membrane); Foerster-Fuchs’ spot (macular hemorrhage); cataract; retinal holes and high risk of rhegmatogenous RD

Lacquer crack: sudden decrease in vision, metamorphopsia, often in teenagers; focal subretinal hemorrhage, dense, round, deep, and often centered on fovea; blood may obscure crack

Complications

CNV often near fovea (65%) worse prognosis; 60% with vision <20/200 at 2 years

Treatment

Same as CNV due to AMD

Other Causes of Macular CNV

Idiopathic, optic nerve head drusen, choroidal rupture, choroidal nevus, sympathetic ophthalmia, Vogt-Kayanagi-Harada disease, serpiginous choroiditis, other posterior uveitides (choroidal inflammation may enhance production of angiogenic factors; when coupled with RPE-Bruch’s membrane disruption, CNV can develop)

Vascular Diseases

Damage to vessel walls causes leakage of serum and blood into plexiform layers, causing edema, exudates, and hemorrhages

Edema

histologically appears as clear cystoid spaces

Lipid

appears as yellow lesion; histologically, hard exudates are eosinophilic and PAS-positive

DDx: diabetes, hypertensive retinopathy, CNV, vein occlusion, parafoveal telangiectasia, Coats’ disease, radiation retinopathy, CSR, trauma, macroaneurysm, papilledema, angiomatosis retinae

Microaneurysm

fusiform outpouching of capillary wall

Cotton wool spot

microinfarction of NFL (usually secondary to occlusion of retinal arteriole) with cessation of axoplasmic flow, mitochondria accumulate (resemble a nucleus, so lesion appears like a cell [‘cytoid body’])

Hemorrhage

shape of intraretinal blood depends on layer in which it occurs (dot / blot in plexiform layer where cells are oriented vertically; flame-shaped / feathery border in NFL where cells are oriented horizontally)

Roth spot

white-centered hemorrhage

DDx: ischemia (anemia, anoxia, carbon monoxide poisoning), elevated venous pressure (birth trauma, shaken baby syndrome, intracranial hemorrhage), capillary fragility (hypertension, diabetes), infection (bacterial endocarditis, HIV), leukemia, collagen vascular disease

Neovascularization

growth of new vessels on vitreous side of ILM; new vessels grow along posterior hyaloid

Vascular tortuosity

may be congenital (arterial and venous) or acquired (venous)

DDx: hypertension, high venous pressure (occlusion), papilledema, high viscosity, AV fistula; associated with fetal alcohol syndrome, Peter’s anomaly, optic nerve hypoplasia

Retinal Vasculitis

Involvement of retinal arterioles (arteritis), veins (phlebitis), or both (periphlebitis)

Findings

sheathing of vessels, hemorrhage

DDx

temporal arteritis, polyarteritis nodosa, lupus, Behçet’s disease, inflammatory bowel syndrome, multiple sclerosis, pars planitis, Wegener’s granulomatosis, Eales disease, sarcoidosis, syphilis, toxoplasmosis, viral retinitis (HSV, HZV), IV drug abuse, Lyme disease, tuberculosis

Cystoid Macular Edema (CME)

Intraretinal edema in honeycomb-like spaces; flower-petal pattern due to Henle’s layer

Pathophysiology

abnormal perifoveal retinal capillary permeability; initial fluid accumulation may be within Müller’s cells (rather than in spaces of outer plexiform and inner nuclear layers)

Findings

CME, optic nerve swelling, vitreous cell (Figure 11-53)

Figure 11-53 Cystoid macular edema with decreased foveal reflex, cystic changes in fovea, and intraretinal hemorrhages.

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

FA

multiple small focal fluorescein leaks early; late pooling of dye in cystoid spaces; classically, flower-petal (‘petalloid’) pattern; staining of optic nerve (Figure 11-54)

Figure 11-54 Fluorescein angiogram of same patient as in Figure 11-53, demonstrating characteristic petalloid appearance with optic nerve leakage.

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

OCT

cystic intraretinal spaces (Figure 11-55)

Figure 11-55 Optical coherence tomography of cystoid macular edema, demonstrating intraretinal cystoid spaces and dome-shaped configuration of fovea.

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

DDx of cystic macular changes (looks like CME clinically, but no fluorescein filling of cysts)

1 Juvenile retinoschisis

2 Goldmann-Favre

3 Some types of RP

4 Nicotinic acid maculopathy

Treatment

depends on etiology; focal laser treatment, topical steroids and NSAID, oral Diamox, sub-Tenon’s or intravitreal steroid injection

Congenital Retinal Telangiectasia / Coats’ Disease (Leber’s Miliary Aneurysms)

(See Ch. 5, Pediatrics / Strabismus.)

Parafoveal / Juxtafoveal Telangiectasia (PFT, JXT)

Microaneurysmal and saccular dilation of parafoveal vessels

Classification

Type 1: unilateral, male > female (10 : 1); onset during middle age; in spectrum of Coats’ disease

TYPE 1A: congenital; confined to temporal half of fovea; macular edema and exudation (lipid)

TYPE 1B: idiopathic; capillary telangiectasia confined to 1 clock hour at edge of FAZ; minimal leakage on FA; occasional hard exudates; vision usually better than 20/25; can be treated with laser

Type 2A (most common): bilateral, acquired; male = female; 5th–6th decade of life; symmetric, involving area <1 DD; minimal macular edema; occasionally, superficial glistening white dots (Singerman’s spots); right-angle retinal venules dive deep into choroid; eventual develop RPE hyperplasia; occasionally, yellow lesion measuring

DD centered on FAZ (pseudovitelliform macular degeneration); may develop macular edema that is due to ischemia (not amenable to laser treatment);

abnormal glucose tolerance test

FA: parafoveal capillary leakage; risk of CNV

Type 3: bilateral, idiopathic; male = female; capillary occlusion predominates

TYPE 3A: occlusive idiopathic

TYPE 3B: occlusive idiopathic; associated with central nervous system vasculopathy

Structural abnormalities in types 2 and 3 are similar to diabetic microangiopathy (but no risk of NVE)

DDx

diabetes, vein occlusion, radiation retinopathy, Coats’ disease, Eales’ disease, Best’s disease, sickle cell, Irvine-Gass syndrome, ocular ischemia

Complications

macular edema, exudates, CNV, intraretinal neovascularization, retinal–retinal anastamosis

Retinal Arterial Macroaneurysm (RAM)

May bleed, then autoinfarcts

Usually, elderly females; most common along temporal arcades; 10% bilateral

Mechanism

arteriosclerosis (fibrosis, thinning, decreased elasticity of vessel wall), hypertension (increased pressure on thin wall)

Findings

blood in every retinal layer, lipid exudate, artery occlusion downstream (especially following laser treatment), CME (Figure 11-56)

Figure 11-56 Macroaneurysm with surrounding dilated and telangiectatic capillary bed:. A, fundus photograph;, B, FA.

(Courtesy Susan Fowell, MD. From Mittra RA, Mieler WF, Pollack JS: Retinal arterial macroaneurysms. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

DDx of blood in every retinal layer (subretinal, intraretinal, and preretinal)

macroaneurysm, trauma, sickle cell retinopathy, choroidal melanoma, vein occlusion (rare), CNV (rare)

Pathology

overall thickening of vessel wall with hypertrophy of muscularis

Treatment

observation; consider focal laser (risk of hemorrhage)

Hypertensive Retinopathy

Focal or generalized vasoconstriction, breakdown of blood–retinal barrier with subsequent hemorrhage and exudate

Associated with microaneurysms or macroaneurysms

Findings

Retinopathy: AV nicking, ‘copper or silver wire’ arterial changes, hemorrhages, exudates, cotton wool spots

Choroidopathy: fibrinoid necrosis of choroidal arterioles; may have Elschnig’s spots (zone of nonperfusion of choriocapillaris; pale white or red patches of RPE), Siegrist streak (reactive RPE hyperplasia along sclerosed choroidal vessel), and exudative RD; due to acute hypertensive episode (pre-eclampsia, eclampsia, or pheochromocytoma); FA shows early hypoperfusion and late staining

Optic neuropathy: florid disc edema with macular exudate, linear flame hemorrhages

Pathology

thickening of arteriolar walls leads to nicking of venules; endothelial hyperplasia

Complications

retinal vein occlusion, retinal macroaneurysm, nonarteritic AION, ocular motor nerve palsies, worsening of diabetic retinopathy

Diabetic Retinopathy (DR)

Leading cause of new blindness in United States, adults aged 20–74 years

Classification

Background or nonproliferative (BDR, NPDR): hemorrhages, exudates, cotton wool spots, microaneurysms (MA), intraretinal microvascular abnormalities (IRMA), venous beading (Figure 11-57)

Severe NPDR (‘4-2-1 rule’) (15% progress to PDR in 1 year):

Defined as any one of the following:

4 quadrants of hemorrhages / MAs

2 quadrants of venous beading

1 quadrant of IRMA (Figure 11-58)

Very severe NPDR (50% progress to PDR in 1 year):

Defined as 2 or more of the above

Proliferative (PDR): NV of disc or elsewhere (Figure 11-59)

High–risk proliferative (HR-PDR):

Defined as any one of the following:

1 NVD ≥

disc area

2 Any NVD with vitreous hemorrhage

3 NVE ≥

disc area with vitreous hemorrhage

Figure 11-57 Nonproliferative diabetic retinopathy.

Figure 11-58 Severe nonproliferative diabetic retinopathy with extensive hemorrhages, microaneurysms, and exudates.

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

Figure 11-59 Proliferative diabetic retinopathy demonstrating florid neovascularization of the disc and elsewhere.

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

Findings

cotton wool spots, lipid exudates (may appear as circinate exudate [ring of hard exudate surrounding leaky focus] or macular star [pattern reflects radial orientation of Henle’s fibers]), hemorrhages (blot [outer plexiform layer], flame [tracks along NFL]), microaneurysms, IRMA (intraretinal microvascular abnormalities; shunts [arteriole to venule]), venous beading and loops, neovascularization (disc [NVD], elsewhere in retina [NVE], iris [NVI]) (Figure 11-60)

Figure 11-60 Fluorescein angiogram of a patient with proliferative diabetic retinopathy, showing extensive capillary nonperfusion, neovascularization elsewhere, and vascular leakage.

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