Geographic atrophy (GA) and drusens are known to be distinguishing features of nonexudative (dry) age-related macular degeneration (AMD). The volume and number of drusen are known to be biomarkers for severity of the disease (Yi et al. 2009). Segmented RPE surface topography maps on macular thickness analyses show contour alteration due to underlying drusens. SD-OCT made possible the ultrastructural characterization of drusen (Khanifar et al. 2008). They are characterized by smooth or jagged elevations of the RPE layer, with varied reflectivity in relation to reflectivity of the photoreceptor layer and RPE (Hee et al. 1996; Srinivasan et al. 2006a). The summed-voxel projection, a representative two-dimensional en face image created by B-scans along the anterior-posterior axis of a three-dimensional OCT stack, orients the drusen seen tomographically, with respect to retinal vasculature seen on fundus photographs. Geographic atrophy results from the loss of the photoreceptor layer, RPE, and choriocapillaris. In most cases, GA first appears in the parafoveal location and progresses around the fovea with concomitant loss of central visual acuity. These are identified on sequential imaging of three-dimensional retinal cube along the orthogonal planes. The RPE contour map gives the complete image of the lateral extent of the atrophy surrounded by a transitional area. In transitional areas the photoreceptor dysfunction precedes the appearance and progression of GA (Curcio et al. 1996). Advanced macular visualization helps identify disruption of inner segment ellipsoid segment (EZ) of photoreceptors along areas of the spread of GA.

In classic neovascularization (CNV), SD-OCT illustrates a hyperreflective mass that extends above the RPE, raising the neuroretina (Fig. 2.3). Intraretinal edema and neovascular mass surrounded by areas of neurosensory or pigment epithelium detachment (PED) indicate active CNV. Occult neovascular membranes are located between the RPE and Bruch’s membrane. Hemorrhagic subretinal fluid and serous elevation of RPE are differentiated on the basis of reflectivity profile. The high resolution of SD-OCT allows precise imaging of minute areas of intraretinal or subretinal fluid and their localization to specific layers. Alterations in ILM-RPE thickness maps with changes in foveal contour and surface alteration of RPE topography map are useful indicators for early identification of occult cases as well as for monitoring progression of CNV. Sequential imaging of the three-dimensional cube in the Z plane provides with en face imaging of the retina at a defined depth especially at the level of RPE. Three-dimensional SD-OCT has superseded fluorescein angiography in subclinical identification of the retinochoroidal anastomosis (Querques et al. 2011). Changes in height of PED, obliteration of subretinal space, and progression of CNV are visual guides on follow-up of cases (Ahlers et al. 2008). RPE tears are known to complicate PED (Chang and Sarraf 2007; Leitritz et al. 2008). Tangential stress on RPE due to the increasing height of RPE detachment, rapid contraction of regressing CNV, and treatment with anti-vascular endothelial growth factor (anti-VEGF) therapy are probable causes of RPE tear (Chan et al. 2007; Chan et al. 2010; Chiang et al. 2008; Gass 1984; Lafaut et al. 2001; Shiraki et al. 2001). Three-dimensional SD-OCT with its unparallel topographical view of retinal layers identifies and localizes RPE tear particularly subclinically (Saxena et al. 2012d). The RPE tear is visualized as absence of RPE underneath the neurosensory retina with focal interruption of the RPE signal and a hyperreflective retracted RPE edge (Fig. 2.4). Associated CNV is responsible for hyperreflection in sub-RPE space. The RPE tear creates an area where photoreceptors have no RPE support affecting the visual acuity, especially in cases where fovea is involved (Albert et al. 2011). With time, fibroproliferative changes obliterate the subretinal space. This has been correlated with histological studies that revealed rolled up margins of the RPE tear along with the fibrovascular membrane over remains of outer segments (Leitritz et al. 2008).

Central serous chorioretinopathy (CSC) is a disorder of RPE-choriocapillaris complex (Spaide 2005). It is characterized by serous detachments of the neurosensory retina (Fig. 2.5). Disruption of the choroidal circulation, followed by decompensation of RPE, allows exudation from the choroidal vasculature to pass into the subretinal space (Guyer et al. 1994; Piccolino et al. 2005; Scheider et al. 1993). Pigment epithelium detachment is not an uncommon finding in these cases and is usually located within or at the edge of the sensory retinal detachment (Figs. 2.5, 2.6). Diffuse RPE atrophy or alterations characterize chronic CSC. Subretinal fluid may be cloudy due to the presence of fibrin in chronic or recurrent cases (Mitarai et al. 2006; Ojima et al. 2007). A better understanding of the pathogenesis has been gained with advent of OCT (Kamppeter and Jonas 2003; Lida et al. 2000; Mitarai et al. 2006; Piccolino and Borgia 1994). SD-OCT succeeded fluorescein angiography by identifying defects in the RPE layer in the areas of PED corresponding to sites of leakage (Fujimoto et al. 2008; Hussain et al. 2006; Montero and Ruiz-Moreno 2005). Three-dimensional OCT localizes these leakage sites precisely (Wang et al. 2011). Three-dimensional surface RPE maps confirm both PEDs and RPE alterations. Surface topography map of ILM reveals the presence and location of subclinical CSC with changes in surface contour. False color-coded ILM-RPE maps provide with progressive analysis of thickness (Fig. 2.6). Subretinal fibrin deposition in chronic CSC has been demonstrated on 3D SD-OCT (Saxena et al. 2011). Hyperreflectivity in the subretinal space with fibrin deposition corresponds to clinically observed yellowish white subretinal exudate (Fig. 2.7).

Alteration in the photoreceptor outer segment (OS) and EZ is visualized inner to the detached neurosensory retina (Ojima et al. 2007). The increased thickness of the OS in acute phase gradually decreases with reattachment. Punctuate or granular appearance of the OS occurs more frequently in cases of chronic or recurrent CSC. The latter appearance is probably due to the accumulation of the shed OS. After retinal reattachment, the EZ gradually becomes clear, implying normalization of the assembly of the OS due to regular phagocytosis resumed by the RPE. Thus a detailed morphological assessment of the disease is obtained.

OCT has been an indispensable ancillary investigation for characterization of intraretinal cystoid spaces in diabetic macular edema. The thickness of the subretinal space is greatest at the central fovea and declines peripherally. Serous retinal detachment is seen as a subretinal fluid accumulation with elevation of neurosensory retina from RPE (Figs. 2.8, 2.9). 3D SD-OCT is a supportive investigative tool for evaluation and follow-up of patients with diabetic retinopathy. Involvement of the outer plexiform layer, inner plexiform, and ganglion cell layer with global extent of edema is well defined with sequential imaging in the three orthogonal planes. Cotton wool spots, due to retinal ischemia, appear as regions of increased reflectivity of the retinal nerve fiber layer and inner neurosensory retina. Hard exudates are identifiable as hyperreflective foci in the outer retinal layers with posterior shadowing. Color-coded retinal thickness maps pick up the earlier stages of diabetic retinopathy with ILM surface topography depicting the absence of foveal depression. RPE changes may also reflect previous laser photocoagulation, which are visualized on RPE segmentation map. High-resolution imaging enables better evaluation of the integrity of the photoreceptor layer, both at baseline and after resolution of diabetic macular edema.

Three-dimensional SD-OCT is an auxiliary investigative tool for portraying neovascularization, hemorrhage, and preretinal fibrosis in proliferative diabetic retinopathy. With imaging of vitreoretinal interface, visualization of subhyaloid hemorrhage relative to the ILM and posterior hyaloid face, extent of the lesion, and structural alteration of layers of the retina below the hemorrhage are well defined (Kroll et al. 1999; Punjabi et al. 2008). Structural changes in the retina below the hemorrhage predict the visual outcome post therapy. Distinction of preretinal membranes, visible as thin reflective bands anterior to the retina, from detached posterior vitreous is made easy. The posterior hyaloid typically has a lower reflectivity than a preretinal membrane due to the optical transparency of the vitreous. Presence, localization, and extent of retinal traction are well visualized (Srinivasan et al. 2006a). Retinal thinning corresponding to retinal atrophy occurs in the region of previous photocoagulation treatment. The vitreous gel plays a key role in causing effects at vitreoretinal interface with fibrovascular proliferation or epiretinal membrane (ERM) formation at later stages of diabetic retinopathy. Presence and severity of macular traction and distortion of retinal contour due to ERM are well studied. Uniform attachment or multiple surface adhesions with retinal striae or focal tenting of the inner retina are better visualized on 3D SD-OCT. Evaluation of vitreoretinal interface has helped better understand the pathophysiology of the disease and planning for surgery (Gallemore et al. 2000).

Occlusion of the retinal venous system is the second most common retinal vascular disease after diabetic retinopathy (Spaide et al. 2003). OCT findings in retinal vein occlusion include cystoid macular edema, ERM, pseudoholes, lamellar holes, and subhyaloid or preretinal hemorrhages (Arevalo et al. 2013; Spaide et al. 2003). The extent of involvement of edema depends on the territory of the occluded vessel. Hemorrhages are localized to the nerve fiber layer and outer plexiform layer. Edematous changes in the inner nuclear and ganglion cell layer appear as diffuse thickening with hyporeflective spaces. Cystic changes localize to the inner and outer nuclear layer, and serous retinal detachments may occur with neurosensory retina detachment from RPE. Alteration in external limiting membrane (ELM) as well as EZ is also observed. With 3D SD-OCT, improved monitoring of macular edema, with changes in retinal contour in response to treatment and correlation with post-resolution visual acuity, has been realized. Spatial extent of macular edema is better discerned with scans along the three orthogonal planes (Yamaike et al. 2008). OCT plays a pivotal role in quantitatively monitoring the changes in retinal thickness after treatment, such as intravitreal triamcinolone or anti-VEGF therapy (Greenberg et al. 2002).

Central retinal artery occlusion is an unfavorable ocular condition that results in profound and permanent loss of vision. On OCT, the affected area demonstrates increased thickness and reflectivity in the inner retina corresponding to edema of the retinal layers. The ganglion cell layer and inner nuclear layer are affected in proportion to the duration of ischemia, whereas outer nuclear and plexiform layers and photoreceptors show no damage (Wojtkowski et al. 2005). Three-dimensional OCT will enhance the irregular macular contour due to ischemia-induced edema of the inner retinal layers. These findings correlate with the histopathology where ischemic necrosis of the inner layers is observed. Hyperreflectivity of the inner retinal layers causes shadowing of the optical signal of the outer layers and RPE/choriocapillaris complex, mimicking retinal edema. The marked difference from retinal edema due to other retinal vascular diseases is lack of cystic spaces of low reflectivity. No correlation has been found with extent of initial macular edema and visual improvement (Schmidt et al. 2006). Branch retinal artery occlusion and cilioretinal artery occlusion shows similar hyperreflectivity localized to the distribution of the artery involved. After the resolution of retinal edema, the inner retina becomes atrophic in a few days due to reperfusion injury (Saxena et al. 2013b). Later on with washout of oxidative stress biomarkers, recovery of retinal thickness termed pseudo normalization, is observed. Retinal atrophy sets in by 3 months with formation of an acellular scar of the inner retinal layers. False color-coded thickness maps are useful in monitoring these changes.

Visualization of vitreofoveal interface with SD-OCT improved the understanding of pathophysiology of progression of a macular hole. Anteroposterior vitreous and tangential traction explain the sequel of subtle changes in the outer retinal layers of the fovea, elevation of foveal contour in the foveal pit region, followed by formation of a foveal pseudocyst that characterizes an impending macular hole. Retinal tissue remains at the base of a pseudocyst. Three-dimensional SD-OCT demonstrates vitreoretinal interface between the cone of the posterior hyaloid and the inner retinal surface of the foveal pit. Three-dimensional views of the ILM show elevation of the roof of the foveal cyst in the foveal pit. Incompletely detached posterior hyaloid exhibits an oblique pull over the retinal surface with a clinical appearance of crescent or horseshoe retinal defect. Full-thickness macular holes are characterized by disruption of retinal layers up to the RPE with involvement of photoreceptor layers (Figs. 2.10, 2.11, and 2.12). Detachment of vitreous from retinal surface at posterior pole and in later stages from the disk is observed. Full-thickness macular holes are visualized as a cone-shaped steepening of the fovea with variation in extent and base. The size of a macular hole has been documented to affect anatomical and visual success post surgery. Variable amount of intraretinal edema surrounding the hole is present with increase in retinal thickness. Disruption of the photoreceptor layer is a useful predictor of visual outcome post surgery (Hangai et al 2007; Inoue et al 2009; Srinivasan et al. 2006a, b). SD-OCT is useful in evaluating the preoperative macular hole configuration and postoperative resolution (Altaweel and Ip 2003; Tilanus et al. 1999; Ullrich et al. 2002).

SD-OCT also improved the differentiation of lamellar holes and pseudomacular holes (Witkin et al. 2006). Lamellar holes earlier defined as defects in the fovea, due to the avulsion of the roof of a cystoid macular edema, is now described on OCT as dehiscence in the inner fovea with intact outer retinal layers at the base of the hole (Haouchine et al. 2004). Macular pseudohole is described as steepening of foveal contour due to ERM contraction and a normal or slightly increased central and paracentral retinal thickness (Haouchine et al. 2004). Three-dimensional volume rendering illustrates the vertical edges of the foveal pit with a U shape of the fovea (Fig. 2.13). Outer retinal layers are intact.

The epiretinal membrane (ERM) is a nonvascular fibrocellular proliferation that develops on the surface of the ILM and causes a spectrum of changes such as increase in retinal thickening, loss of foveal contour, distortion of the retinal surface, vascular tortuosity, cystic changes, intraretinal fluid accumulation, foveoschisis, and formation of macular pseudoholes. ERM in healthy eyes is localized between ILM and the vitreous body interface (Koizumi et al. 2008). From cellophane macular reflex to macular pucker, ERM has been classified on clinical as well as on OCT findings (Gass 1997; Mori et al. 2004; Wilkins et al. 1996). SD-OCT, besides detecting the focal and broad-based attachments of the ERM to the retina, enhances the resolution of intraretinal architectural morphology (Fig. 2.14). Retinal thickness and integrity of the EZ are known to be prognostic factors of visual acuity after ERM surgery (Wong et al. 2005). Thicker and opaque membranes may cause partial posterior vitreous detachment with persistent vitreomacular adhesions leading to cystoid macular edema. Posterior vitreous detachments also may cause tractional retinal detachment or retinal breaks. Absence of posterior vitreous detachment helps differentiate vitreomacular traction from idiopathic ERM, although both the entities significantly overlap (Koerner and Garweg 1999; Legarreta et al. 2008). ERM with vitreomacular and vitreopapillary adhesions has been described in diabetic retinopathy and Eales’ disease (Ophir and Martinez 2011; Saxena et al. 2012a). With three-dimensional imaging in diabetic retinopathy, ERM with nontractional vitreoretinal interfaces were identified as fine foldings seen on ILM maps, which disappeared after ILM peeling (Abe et al. 2013). ILM segmentation maps demonstrate parallel or radiating folds due to vitreoretinal interaction at sites of adhesion of ERM. Color-coded ILM-RPE thickness maps identify intraretinal fluid accumulation causing elevation of foveal contour (Fig. 2.15). Three-dimensional imaging allows better characterization of ERM including visualization of extent of ERM, cleavage planes formed between retinal layers, evaluation of vitreoretinal surface for attachment sites and its configuration, and assessment of thickness of the ERM (Elbendary 2010). The identification of presence and localization of adhesions of ERM to inner retina help in preoperative planning in membrane peeling or delamination. Sequential imaging of the retinal cube in all the three planes gives a high-resolution representation of all the intraretinal layers identifying extent and location of alteration in functionally relevant structures including the photoreceptor layer. Restoration of the anatomy post surgery can be well demonstrated on OCT. Three-dimensional SD-OCT gives unprecedented visualization of ERM (Figs. 2.13 and 2.14).

Vitreomacular traction (VMT) is a distinct clinical entity which results from persistent attachment of vitreous to the macula in the presence of incomplete posterior vitreous detachment. Asymptomatic disease course of VMT occurs due to spontaneous detachment of vitreous from macula with restoration of structural retinal changes (Hikichi et al. 1995). Persistent traction leads to structural changes of retinal contour with progressive retinal edema, distortion of retinal architecture, detachment of fovea, or full-thickness macular hole formation (Gallemore et al. 2000; Yamada and Kishi 2005). Vitreopapillary adhesion may influence the vectors of force at the vitreoretinal interface causing a centrifugal tangential contraction which can result in idiopathic ERM (Wang et al. 2009). Coexisting macular diseases classifies VMT as concurrent. Vitreopapillary and vitreomacular traction have been described in diabetic retinopathy (Karatas et al. 2005; Ophir and Martinez 2011; An OCT based classification by the International Vitreomacular Traction study group subclassified VMT with attachment of 1500 μm or less as focal, whereas VMT with attachment of more than 1500 μm as broad (Duker et al. 2013). Three-dimensional imaging gives a comprehensive view of vitreoretinal interface changes and a global perspective to the structural alteration of retinal layers caused by VMT (Ito et al. 2000; Chang et al. 2008). SD-OCT discerns retinoschisis of the outer retinal layers. Structural alteration of the photoreceptor layer correlates well with visual dysfunction, metamorphopsia. Surface topography ILM map shows corresponding elevation of ILM at the points of vitreous attachments at foveal and extrafoveal locations. A cleavage plane due to infolding of the retina can be observed as a corresponding dip over the ILM map. A false color-coded ILM-RPE map highlights the changes in macular thickness. Introduction of ocriplasmin, a pharmacological means of vitreolysis, has increased the significance of evaluation of the vitreomacular interface with SD-OCT. A detailed evaluation of the attachment site reinforces the role of 3D OCT in identifying suitable cases for ocriplasmin therapy (Figs. 2.16, 2.17, and 2.18).

Eales’ disease is an idiopathic inflammatory venous occlusive disease and primarily affects the peripheral retina of young men. It is characterized by stages of venous inflammation (periphlebitis), peripheral capillary nonperfusion, and retinal neovascularization. SD-OCT offers high-resolution imaging of the retina in cases of Eales’ disease. Appreciation of ERM, retinal folds, and hyperplastic RPE are well discerned. Retinoschisis in a case of Eales’ disease has also been detected with the help of SD-OCT (Saxena and Kumar 2000). Saxena and Kumar have also reported the involvement of macula in Eales’ disease. Vitreopapillary and vitreomacular tractions with ERM leading to vitreomaculopathy have been documented (Saxena et al. 2012a). Anomalous posterior vitreous detachment is not the cause of vitreomacular or vitreopapillary traction in these cases. Microstructural changes in the retina due to vector forces of the fibrous traction bands are well discerned with the help of three-dimensional SD-OCT (Fig. 2.19). The ILM-RPE segmentation maps are useful in depicting the topographical changes due to traction caused by fibrous bands. These maps reveal the surface alterations on the retina, internal limiting membrane, and the changes in retinal thickness.

Stargardt disease (STGD) is an autosomal recessive macular dystrophy, linked to mutation of the ABCA4 gene, characterized by early onset, rapid progression, and poor visual outcome. Fundus flavimaculatus (FFM) is a variant dystrophy with late onset and slow progression. The ABCA4 gene codes for a transport protein that is involved in the visual cycle and located in the photoreceptor outer segments. Mutation in ABCA4 results in abnormal accumulation in RPE and consequent RPE degeneration and photoreceptor disruption. Both dystrophies are characterized by macular atrophy and fleck-like deposits in the retina of varying size and shapes (Querques et al. 2006). SD-OCT is helpful in these cases in revealing photoreceptor disruption and appropriate localization of the flecks in different layers of the retina and their anatomic configuration with one another (Querques et al. 2009). Voigt et al. (2010) demonstrated presence of flecks at five different levels in FFM. They reported flecks at the level of outer segment of the photoreceptors, the RPE interdigitations, at and beneath the RPE/Bruch membrane complex, interface of photoreceptors and external limiting membrane, and a few flecks at the level of outer nuclear layer. Verdina et al. (2012) showed the absence of isolated flecks at ONL and reported that there was a presence of anatomical connection between all the hyperreflective flecks at the level of ONL with the one present at the level of RPE. These represent the different appearances or stages of the same lesion. On SD-OCT, flecks at the level of RPE correspond to areas with disruption of ellipsoid zone of the photoreceptor.

Three-dimensional SD-OCT imaging provides novel insight into the in vivo retinal morphology and pathogenesis of STGD and FFM (Saxena et al. 2012e). The atrophic area in fovea may be surrounded by a transition zone which is hypothesized to represent areas in the process of photoreceptor disruption. Macular visualization on SD-OCT demonstrates central macular atrophy with loss of the photoreceptor layer, marked thinning of outer nuclear layer, and residual neurosensory retina. Peripheral retinal layers are structurally normal. Segmentation maps provide ancillary findings. The ILM-RPE thickness maps reveal two concentric ring-like patterns for the two zones in both STGD and FFM. The inner zone of accentuated foveal depression, surrounded by an outer transitional zone, is visualized. Analysis of a single ILM map gives a better definition of the two zones in the case of FFM as compared to STGD. A segmentation map of RPE demonstrates the flecks as surface irregularities. The distribution of flecks on a RPE topography map further distinguish the two variants; a widespread distribution of flecks all over the posterior pole is a feature of STGD, whereas in FFM, flecks are present only along the vascular arcades. Irregular hyperreflectivity below the RPE was more prominent in the subfoveal area in the case of Stargardt (Figs. 2.20 and 2.21).