Ординатура / Офтальмология / Английские материалы / Oxford American Handbook of Ophthalmology_Tsai, Denniston, Murray_2011

.

Anatomy and physiology

The retina is a remarkable modification of the embryonic forebrain that gathers light, codes the information as an electrical signal (transduces), and transmits it via the optic nerve to the processing areas of the brain.

Embryologically, it is derived from the optic vesicle (neuroectoderm), with an outer wall that becomes the retinal pigment epithelium, a potential space (the subretinal space), and an inner wall that becomes the neural retina.

Anatomy

Retinal pigment epithelium (RPE)

The RPE is a monolayer of hexagonal cells. The apices form microvilli that envelop the photoreceptor outer segments. Near the apices, adjacent RPE cells are joined by numerous tight junctions to form the outer blood– retinal barrier.

The base of the RPE is crenellated (to increase surface area) and mitochondrion rich. The basement membrane of the RPE forms the inner layer of Bruch’s membrane. Anteriorly, the RPE is continuous with the pigmented layer of the ciliary body.

Neural retina

This is a 150–400 μm thick layer of transparent neural tissue, comprising photoreceptors (rods, cones), integrators (bipolar, horizontal, amacrine, ganglion cells), the output pathway (nerve fiber layer), and the support cells (Müller cells). Anteriorly, the neural retina is continuous with the nonpigmented layer of the ciliary body.

The macula is defined histologically by a multilayered ganglion cell layer (i.e., more than one cell thick) and approximates to a 5500 μm oval centered on the fovea and bordered by the temporal arcades. It is yellowish from the presence of xanthophyll. The macula is further divided into perifovea (1500 μm wide band defined by 6 layers of bipolar cells), parafovea (500 μm wide band defined by 7–11 layers of bipolar cells), and fovea (1500 μm diameter circular depression). The fovea comprises a rim, a 22* slope, and a central floor, the foveola (350 μm diameter, 150 μm thin). The umbo is the center of the foveola (150 μm diameter); maximal cone density equates to highest acuity.

Blood supply

Branches of the ophthalmic artery include the central retinal artery, which supplies retinal circulation, and the three posterior ciliary arteries, which provide choroidal circulation. Anatomically, the retinal circulation supports the inner two-thirds of the retina, whereas the choroidal circulation supports the outer third; the watershed is at the outer plexiform layer. Physiologically, this equates to two-thirds of the retina’s oxygen and nutrient requirements being supplied by the choroidal circulation.

The retinal circulation comprises a small part of ocular blood flow (5%) but with a high level of oxygen extraction (40% arteriovenous difference), contrasting with figures of 85% and 5% for the choroidal circulation. In the retinal circulation, the arterial branches lie in the nerve fiber layer but give rise to both an inner capillary network (ganglion cell layer) and an outer

.

ANATOMY AND PHYSIOLOGY 407

capillary network (inner nuclear layer). However, there are no capillaries in the central 500 μm, the foveal avascular zone (FAZ).

The outer blood–retinal barrier is formed by the tight junctions of the RPE cells, whereas the inner is formed by the nonfenestrated endothelium of the retinal capillaries.

Physiology

RPE

The RPE is vital to the normal function of the neural retina. Functions include maintenance of the outer blood–retinal barrier, maintenance of retinal adhesion, nutrient supply to the photoreceptors, absorption of scattered excess light (by melanosomes), production and recycling of photopigments, and phagocytosis of damaged photoreceptor discs (each sheds >100 discs per day).

Neural retina

Each human eye contains around 120 million rods and 6.5 million cones. The rods subserve peripheral and low-light (scotopic) vision, whereas the cones permit normal (photopic), central, and color vision. The rods reach their highest density at 20* from the fovea, in contrast to blue cones, which are densest in the perifovea, and red and green cones, which are densest (up to 385,000/mm2) at the umbo.

The outer segments of photoreceptors contain transmembrane photopigment molecules (rhodopsin in rods, iodopsins in cones) that undergo cis-trans isomerization on absorption of a photon of light (440–450 nm for blue, 535–555 nm for green, and 570–590 nm for red cones).

Activation of a single photopigment molecule starts a cascade of activation (transducin activates phosphodiesterase which in turn hydrolyses cGMP) with 100-fold amplification at every stage. Falling cGMP levels cause closure of Na channels, with photoreceptor hyperpolarization. The resting potential is then restored by the action of recoverin, which activates guanylate cyclase to cGMP and reopen Na channels.

Rods synapse with “on” bipolar cells, which in turn synapse with amacrine and ganglion cells. Cones synapse with “on” and “off” bipolar cells, which in turn synapse with “on” and “off” ganglion cells. Negative feedback is provided by the laterally interacting horizontal cells (between photoreceptors) and amacrine cells (between bipolar cells and ganglion cells). This contributes to the center-surround phenomenon exhibited by ganglion cells in which they are activated by stimulation in the center of their receptive field but inhibited by stimulation of the surround. Ganglion cell representation is maximal at the fovea, where the cone: ganglion cell ratio approaches 1:1.

Ganglion cells are divided into two main populations. The parvocellular system subserves fine visual acuity and color. These cells are mainly foveal, have small receptive fields, and show spectral sensitivity. The magnocellular system subserves motion detection and coarser form vision. These ganglion cells are mainly peripheral, have larger receptive fields and high luminance and contrast (but no spectral) sensitivity, and are sensitive to motion. This division is preserved in the lateral geniculate nucleus (layers 1–2 magnocellular, 3–6 parvocellular) and visual cortex.

.

Age-related macular degeneration (1)

Age-related macular degeneration (AMD) is the leading cause of blindness for those over age 50 in the Western world. Its prevalence increases with age. Estimates vary according to the exact definition of AMD. One study found visually significant disease (VA 20/30) in around 1% for age 55–65 years, 6% for 65–75 years, and 20% for >75 years.

Drusen (not necessarily with dVA) are increasingly common with age. Other risk factors include gender (female > male), ethnic origin (white >> black), diet, cardiovascular risk, smoking, pigmentary changes in the macula, family history of macular degeneration, and hypermetropia.

Non-neovascular (dry) AMD

Accounting for 90% of AMD, this tends to lead to gradual but potentially significant reduction in central vision. It is characterized by drusen (hard or soft) and RPE changes (focal hyperpigmentation or atrophy).

Histology

There is a gradual loss of the RPE/photoreceptor layers, thinning of the outer plexiform layer, thickening of Bruch’s membrane, and atrophy of choriocapillaris, exposing the larger choroidal vessels on examination.

Drusen are PAS-positive amorphous deposits lying between the RPE membrane and the inner collagenous layer of Bruch’s membrane; they may become calcified. Additional abnormal basement membrane deposit lies between the RPE membrane and RPE cells; it is not visible clinically.

Clinical features

•dVA, metamorphopsia, scotomas; usually gradual in onset.

•Hard drusen (small, well-defined, of limited significance), soft drusen (larger, poorly defined, increased risk of CNV), RPE focal hyperpigmentation, RPE atrophy (“geographic” if well-demarcated) (see Fig. 13.1).

Investigation

FA is not usually necessary. Fundus autofluorescence is useful for delineating the area of disease and following disease progression.

Treatment

•Supportive: low vision aid counseling, and linking to support group and social services.

•Refraction: with increased near-add; low-vision aid assessment and provision are often best arranged in a dedicated low-vision clinic.

•Intraocular telescope: implantable telescope after cataract extraction can provide patients with moderate disease an enlarge image for reading daily activities within a 3 meters range; patient selection is highly important for this procedure.

•Amsler grid: regular use of an Amsler grid allows the patient to detect new or progressive metamorphopsia, prompting him/her to seek ophthalmologic examination.

•Lifestyle changes: vitamin supplementation (AREDS formula) and smoking cessation may slow progression.

.

Age-related macular degeneration (3)

Differential diagnosis of CNV

Table 13.1 Common causes of CNV