The mechanism and pathogenesis of amblyopia is an area of vast interest, with hundreds of publications produced on the topic in the last four decades. A common question that remains to be answered fully is the exact location of the disturbance within the visual system that is responsible for ultimately producing amblyopia. Changes have been found in the lateral geniculate nucleus (LGN) and visual cortex. It has been shown that the amblyopic eye functions at its best in mesopic and scotopic conditions and at its worst under photopic conditions. Retinal receptive fields in amblyopic eyes have also been shown to be larger than normal (14). Lastly, contrast-sensitivity function measured at the foveal region in strabismic amblyopes is reduced and similar to contrast-sensitivity function measured from the peripheral retina of a normal eye (15).

While amblyopia is most often detected during visual acuity testing, reduction in visual acuity is not the only visual abnormality that is present in the amblyopic eye. The full range of abnormalities present in the amblyopic eye has probably yet to be identified. Known visual abnormalities include reduced contrast sensitivity, dark adaptation abnormalities, and visual field abnormalities. Even the “sound” eye has been shown to have abnormalities in patients with anisometropic amblyopia. Leguire (16) reported reduced contrast-sensitivity function in both the amblyopic and “sound” eye of amblyopic patients. Kandel (17) reported dark adaptation to be better in the nonamblyopic eye.

Some authors have proposed that most eyes with amblyopia actually have subtle, undiagnosed ocular pathology involving the optic nerves, such as mild optic nerve hypoplasia (18). Certainly, it is true that some children initially diagnosed with amblyopia are later found to have subtle eye pathology when cooperative enough in later life to undergo a more detailed examination. The possibility of occult optic nerve and/or retinal pathology should always be kept in mind during the management of children with amblyopia who are not responding to treatment as anticipated.

Amblyopia is associated with histologic and electrophysiologic abnormalities in the visual cortex. Hubel and Wiesel (19) pioneered methods of studying the effects of changing visual experience in kittens by suturing an eyelid closed. Similar results have been found in a primate model (20). In these and other experiments, amblyopia was produced by suturing the lids closed in one eye and by inducing experimental anisometropia in susceptible animals.

The layers of the LGN corresponding to input from the amblyopic eye have also been shown to be attenuated in monkeys with strabismic, anisometropic, and visual-deprivation amblyopia (Fig. 6.1). Cells from the LGN travel through the parietal or temporal lobes to the visual
cortex, located in the occipital lobes. Ocular dominance columns representing alternating input from the right and left eyes are present in all portions of the visual cortex that receive binocular input. Notable exceptions are the temporal crescents of retina in each eye and retina corresponding to the position of the optic nerve in the fellow eye, which contribute monocular input. Amblyopia is associated with a decrease in the number of binocularly driven cells in the striate cortex (20,21). In a monkey model with deprivation amblyopia, the ocular dominance columns associated with the amblyopic eye were shown to be markedly attenuated (Fig. 6.2). These cortical changes presumably become irreversible over time. Recently Demer and coworkers (22) demonstrated significant reduction in relative cortical blood flow and glucose metabolism during visual stimulation of the amblyopic eye during a positron emission tomography scan.