Spectral domain-OCT can be used to monitor RP-related changes in the retinal layers including the photoreceptor layers (represented by the EZ), the ELM and the retinal nerve fibre layer (RNFL) (Hood et al. 2009; Triolo et al. 2013). A previous study demonstrated that the loss of the EZ can be directly related to the inner abnormal FAF border of the ring as well as visual field boundary. Ellipsoid zone loss may be patchy and incomplete in the early stages and become complete in the later stages. Correspondingly, in the early stages, the central cone photoreceptors may be spared. A loss of the ELM was also noted in some patients. In some cases thinning of the RPE/Bruch’s membrane complex has also been observed (Fig. 24.1b) (Hood et al. 2009; Hood et al. 2011a, b; Murakami et al. 2008; Triolo et al. 2013; Wakabayashi et al. 2010). Changes affecting the inner retina have also been reported: The RNFL has been noted to be thicker in RP patients when compared to controls (Fishman 1985). In addition, thinning of the inner retinal layers has also been found to occur at a faster rate in RP patients compared to normal subjects (Oishi et al. 2013).

Hyper-reflective foci in the inner nuclear layer (INL) in early stages followed by changes in the outer nuclear layer (ONL) in later stages have been described. These hyper-reflective foci are thought to be indicative of structural retinal changes (Figs. 24.3b and 24.4b) (Kuroda et al. 2014). Optical coherence tomography can aid in the detection of complications associated with RP, such as cystoid macular oedema (CMO), epiretinal membrane and macular hole formation. OCT can be used to monitor the response to treatment with medication or surgery (Hajali and Fishman 2009; Hajali et al. 2008; Hagiwara et al. 2011). In RP patients with severe CMO, visual impairment is strongly correlated to a disruption of the EZ (Fig. 24.3b) (Kim et al. 2013). After cataract surgery about 14 % of RP patients have macular oedema (Jackson et al. 2001). OCT is also useful to detect and monitor the response to treatment of CMO with acetazolamide (Chung et al. 2006).

Overall OCT imaging shows that disruption in the EZ, loss of the ELM and thinning of the inner retinal layers correlate to visual impairment in patients with RP. Choroidal thinning was also observed in both the subfoveal and peripheral retina; however there was no correlation to visual acuity (Dhoot et al. 2013). Optical coherence tomography imaging in combination with FAF imaging, electrophysiology and visual field testing are useful modalities to diagnose as well as monitor progression and response to treatment in patients with RP (Birch et al. 2013; Hood et al. 2011a, b).

Cone dystrophy is a group of heterogenous conditions which predominantly affect the cone photoreceptors. Common symptoms include central vision loss, photophobia, dyschromatopsia and in some cases nystagmus (Michaelides et al. 2004a; Simunovic and Moore 1998). There are two types of cone dystrophy: stationary and progressive. Achromatopsia refers to early-onset cone dystrophy that is usually stationary. The majority of achromatopsia is inherited in an autosomal recessive manner. Blue cone monochromacy is a small subset of stationary cone dystrophy which is inherited in an X-linked recessive manner. Progressive cone dystrophy is most commonly inherited in an autosomal dominant manner. In the progressive form, visual acuity continues to deteriorate gradually, often resulting in legal blindness by adulthood (Jacobson et al. 1989; Ripps et al. 1987). Cone-rod dystrophy appears to involve only cones early in the disease, with progressive rod dysfunction developing later.

Characteristic clinical signs include the presence of a bull’s eye appearance (Fig. 24.7a) with a dark central area at the fovea with surrounding pale zone (Grey et al. 1977). Other non-specific changes that may occur include macular retinal atrophy and pigment deposits. In the later stages, if there is rod involvement, vessel attenuation and bony spicule pigmentation in the periphery may develop. In advanced stages, severe diffuse chorioretinal atrophy, temporal disc pallor and even optic atrophy can occur (van Huet et al. 2013; Michaelides et al. 2004a, b; Simunovic and Moore 1998).

Visual symptoms may precede visible changes in the macula. Associated visual field defects include a central scotoma, an annular scotoma, a generalised sensitivity loss or uncommonly, a peripheral scotoma (Michaelides et al. 2004a, b; Sadowski and Zrenner 1997; Zahlava et al. 2014). Typical electrophysiology findings in cone dystrophy include poor photopic and 30Hz flicker responses, with relatively preserved scotopic (rod-derived) responses. Multifocal electroretinogram also shows a reduction in the amplitude and delay in responses. Electroretinogram (ERG) findings are very informative as they may be abnormal even before any distinguishable clinical signs appear (Fig. 24.5). In the late stages of cone-rod dystrophy, completely undetectable waveforms maybe observed in both scotopic and photopic testing (Krill et al. 1973; Michaelides et al. 2004a, b; Ripps et al. 1987; Sadowski and Zrenner 1997; Simunovic and Moore 1998). Findings with FAF imaging can be variable, but a ring of hyper-autofluorescence surrounded by an area of macula RPE atrophy is commonly seen (Fig. 24.7a) (Robson et al. 2010).

Stargardt disease and fundus flavimaculatus are variants of an inherited form of macular dystrophy. The recessive form caused by mutations in the ABCA4 gene located on chromosome 1p13 is the most common form (Armstrong et al. 1998; Gerber et al. 1995; Hadden and Gass 1976). It has a prevalence of 1 in 10,000. Affected individuals usually present with visual loss in childhood to early teens and many progress to legal blindness by adulthood. A subset of these patients has the onset of disease at a later age, which is often associated with a better visual prognosis. Clinical symptoms include loss of central vision and dyschromatopsia. Fundus examination during the early stage of the disease can be normal, or show non-specific mottling only. As the disease progresses, loss of the foveal reflex and granulation in the RPE with a “snail slime” appearance can be seen (Figs. 24.8a and 24.9a). In the later stages, atrophy of the RPE may give rise to a “beaten bronze” appearance (Cibis et al. 1980; Eagle et al. 1980; Fujinami et al. 2013a, c; Michaelides et al. 2003; Rotenstreich et al. 2003). A characteristic finding of this disease is the bilateral white-yellowish deep retinal lesions (flecks) seen in the posterior pole which can extend to the mid-periphery (Fig. 24.8a). Flecks can vary in shape (e.g. pisciform), size and pattern (Armstrong et al. 1998).

Different FAF imaging patterns have been observed according to the stage of the disease and the rate of atrophy. During the early stages, increased autofluorescence can be seen within the flecks, which reflect the accumulation of autofluorescent material surrounded by a homogeneous background. This background signal can progress to become more heterogenous, developing numerous foci of abnormal signals. In later stage, with increasing atrophy, multiple areas of reduced autofluorescence in the posterior pole can be seen (Fig. 24.8a) (Fujinami et al. 2013a, b, c).

Electrophysiology testing demonstrates macular dysfunction in all cases. In addition, three patterns have been observed, which may have prognostic value: (1) severe abnormality on pattern ERG (macular function) with normal scotopic and photopic b-wave amplitudes, (2) reduced macular function with loss of photopic ERG responses (cone dysfunction) and (3) reduced photopic, scotopic and macular responses which showed global photoreceptor dysfunction of cones and rods (Lois et al. 1999). Long-term prognosis is worst in patients with global photoreceptor dysfunction in addition to maculopathy.

Fundus fluorescein angiography (FFA) shows a characteristic dark choroid with reduced visibility of the choroidal circulation. Newly formed flecks are not fluorescent as the lipofuscin is intracellular; however as the disease progresses, hyperfluorescence occurs due to a window defect in the preretinal and retinal phases (Anmarkrud 1979).

Bietti crystalline dystrophy (BCD) is a rare type of chorioretinal degeneration, characterised by yellow-white dot crystalline deposits seen in the paracentral and peripapillary retina occasionally associated with similar crystalline deposits in the cornea. Other retinal changes include progressive atrophy of the RPE and choroid with pigment clumping (Fig. 24.10a) (Bernauer and Daicker 1992; Mansour et al. 2007; Mauldin and O’Connor 1981). Rarer complications include CMO, choroidal neovascular membrane and macula hole formation (Yin et al. 2014). Symptoms include nyctalopia, decreased visual acuity and a paracentral scotoma that usually presents between the second and fourth decades of life and often continue to progress to severe visual loss, constricted visual fields and legal blindness later in life (Chen et al. 2013; Kojima et al. 2012; Yin et al. 2014). Bietti crystalline dystrophy has been reported to be more common among the oriental race in East Asia and is caused by mutations in the CYP4V2 gene, which causes abnormal lipid metabolism (Kaiser-Kupfer et al. 1994; Rossi et al. 2013; Toto et al. 2013; Yin et al. 2014).

Fundus autofluorescence imaging shows the presence of hypo-autofluorescent areas corresponding to areas of atrophy in the RPE and choroid (Fig. 24.10a). Hyper-autofluorescent spots are seen in the areas of the crystalline deposits only in some cases (Halford et al. 2014). Electrophysiology testing shows decreased amplitudes in both the scotopic and photopic responses with less-affected implicit times. However, there have also been reports of full-field ERG responses remaining normal even in the later stages of the disease. Multifocal ERG can show decreased amplitude in all rings. Visual field loss is also variable and may be in the form of ring, paracentral or central scotoma (Rossi et al. 2013; Sen et al. 2011). Indocyanine green angiography (ICGA) shows disruption in the choroidal circulation with delayed choroidal filling (Fong 2009).

Best’s vitelliform macular dystrophy (BVMD) is an autosomal dominant inherited condition with a variable penetrance. Patients with BVMD typically present in the first and second decades with metamorphopsia and progressive impairment of their central vision. Functional visual acuity is usually able to be preserved in at least one eye even in adulthood (Fishman et al. 1993; Mohler and Fine 1981; Ponjavic et al. 1999; Sohn et al. 2009). Mutations in the Best1gene on chromosome 11q12–q13 have been found to cause changes in the bestrophin-1 protein located in the RPE. This defective protein expresses properties of Ca²⁺-activated Cl⁻ channels, which may explain the underlying pathogenesis of this disease (Rosenthal et al. 2006; Sun et al. 2002).

Juvenile BVMD has been characterised by the deposition of subretinal lipofuscin-rich material in the macula. Five stages have been observed as the disease progresses: (1) previtelliform stage (normal macula or subtle RPE changes), (2) vitelliform stage (Fig. 24.11a, right) (well-defined “egg yolk” lesion), (3) pseudohypopyon stage (Fig. 24.12a, right) (the yellow material settles inferiorly), (4) vitelliruptive stage (Fig. 24.12a, left and 24.13a, left) (a scrambled egg lesion with partial resorption of the material) and (5) atrophic stage (macular atrophy) (Fig. 24.13a, right) (Gass 1977; Mohler and Fine 1981; Querques et al. 2009a). Rupture of the Bruch’s membrane with the development of choroidal neovascularisation (CNV) (Fig. 24.11a, right) can also occur (Noble 1978). Treatment of these secondary choroidal neovascularisations with photodynamic therapy and intra-vitreal anti-vascular endothelial growth factor (Anti-VEGF) has been reported to achieve good results (Andrade et al. 2003; Chung et al. 2001; Querques et al. 2008). Multifocal vitelliform lesions have also been reported (Boon et al. 2007a, b; Querques et al. 2009b). Late stages include fibrosis and geographic atrophy (Mohler and Fine 1981; Querques et al. 2009a).