**6. Application area of OCT in AMD**

#### **6.1. Overview**

Most cases of neovascular AMD are complicated by intraretinal fluid accumulation and RPE detachments. For many years, the therapeutic decision in neovascular AMD was based on the results of fundus biomicroscopy, fluorescein and indocyanine green angiography. In this context, the posttherapeutical evolution in many CNV membranes remained unsatisfactory. OCT technology offers subtle imaging of CNV membranes that appear as hyperreflective bands on OCT. Frequently, the identification of CNV depends on the reflectivity of the adja‐ cent structures and on the CNV localization related to it. OCT is more sensitive than biomi‐ croscopy in identifying retinal edema and small neurosensory and RPE detachments. The OCT relationship with fundus biomicroscopy and fluorescein angiography (FA) in AMD pa‐ tients is summarized in table 3 [8].

OCT is more reliable than biomicroscopy in assessing the macular thickness and small neurosensory and RPE detachments.

OCT is more reliable than FA in identifying the intraretinal and subretinal fluid, as on FA the fluid in the inner retina can mask the fluid in the outer retina.

**6.3. OCT imaging of CNV**

lar membranes.

In neovascular AMD, the retina is invaded by new vessels originating in the choroidal ves‐ sels. According to the relationship of these new vessels with the retinal architecture, wet AMD presents in two forms: classic CNV and occult CNV. The histopathological studies proved that in classic CNV the new vessels penetrate Bruch's membrane, the RPE and the neural retina, whereas in occult CNV they are located between the RPE and Bruch's mem‐ brane, with subsequent loss of RPE barrier function. In classic CNV the RPE is elevated by exudates, blood and lipids located in the subretinal space and having the origin in the new vessels. The occult CNV can be further divided in two forms: with or without serous pig‐ ment epithelial detachment [20] (Table 4). Cystoid macular edema was statistically strongly correlated with the classic form of choroidal neovascularization, whereas the absence of cys‐ toid macular edema was statistically strongly correlated with the occult choroidal neovascu‐

RPE elevated by blood, exudates, lipids

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141

Without PED

New Insights into the Optical Coherence Tomography – Assessement and…

**CNV type Location of the new vessels Clinical findings**

neural retina

Occult Between Bruch's membrane and RPE With PED

**Table 4.** Summary of CNV types – correlation of the histopathological and clinical findings

Occult CNV were described initially on fluorescein angiography (FA) and then on indocya‐ nine green angiography (ICGA) that detected them more accurately, mainly if Scanning La‐ ser Ophthalmoscopy (SLO) was also used. In the recent years, OCT proved its usefulness in defining the features of occult CNV. The main OCT finding that defines occult CNV is the RPE elevation that is separated from the underlying choroidal plane. The cavity formed by the RPE elevation is most frequently fibrovascular and therefore coloured in green, but it can also be serous and then appears optically empty. The RPE elevation is poorly delineated and its extent is variable according to the stage of the lesion. In occult CNV, the RPE eleva‐ tion can be associated with other OCT signs: modifications of the RPE band (hyperreflectivi‐ ty, fragmentations, thickening, thinning), subretinal and intraretinal accumulation of fluid,

**6.4. OCT in the evaluation of the therapeutical response to photodynamic therapy in wet**

OCT helped to better describe the response to treatment in wet AMD. For instance, the response to photodynamic therapy takes place in 5 stages: in the first stage, there is a mild fluid accumulation that corresponds to an acute inflammatory reaction after PDT. Approximately 4 weeks after the first treatment, if there is fluid accumulation, retreat‐ ment is suggested. Typically, the fluid accumulates in the subretinal space, causing the

Classic Penetrate Bruch's membrane, RPE,

vitreomacular traction syndrome [21].

**AMD**

OCT is less precise in evaluating the geographic extent of fluid within the macula, as compared to FA.

Due to the cross-sectional imaging, OCT allows the localization of a CNV in relationship with the RPE and the neurosensory retina.

OCT is superior to FA in identifying CNV membranes that are obscured by pooling of dye or by tiny retinal haemorrhages.

Cystoid macular edema is strongly associated with the classic CNV.

OCT is very useful in AMD monitoring and decision-making after treatment: if fluid persists, re-treatment is indicated.

**Table 3.** Place of OCT in the ophthalmic evaluation of the AMD patients – summary for the clinician

#### **6.2. OCT measurement of macular thickness**

In AMD, the most important clinical parameter is the central macular thickness. OCT is the most precise method to measure retinal thickness in vivo. However, OCT measure‐ ments cannot be correlated exactly to the histopathologic ones, because OCT signals are directly determined by the optical properties of tissues. Therefore, structures that stain strongly on the histopathological specimens do not necessarily appear as intense OCT signals. It has been demonstrated that there are differences in the retinal thickness measurements between OCT models, possibly explained by the higher axial and trans‐ verse resolution of the newer devices. For instance, a comparison was made between Cirrus and Stratus OCT devices in measuring the macular thickness [19]. Firstly, the definition of the retinal boundaries used by the automated segmentation algorithms dif‐ fers between devices [19]. According to the manufacturer, the Stratus OCT program measures between the nerve fiber layer and the inner boundary of the RPE complex, though it has been reported that Stratus OCT has two outer reference lines: one at the junction between the inner/outer segment of the photoreceptor cells and the other at the inner boundary of the RPE. The Cirrus OCT program measures the retinal thickness be‐ tween the nerve fiber layer and the outer band of the RPE. In consequence, the Cirrus outer reference band is deeper than the first mentioned Stratus external band and is closer to the second mentioned one. The correlation of thickness measurements between the two devices is modest, as the Cirrus OCT provides greater measurement depth. The practical implications are targeted towards the clinical practice (the patients participat‐ ing in clinical trials may not interchange between Stratus and Cirrus OCT systems, pa‐ tients transiting from one practice to another should have the tests done with the same OCT model) and the manufacturer (upgradation of Stratus OCT software). Secondly and more importantly, the TD-OCT calculates the retinal thickness based on 6 radial line scans, whereas SD-OCT uses data of 3D scan with 128-200 scans over the same area [19]. Thus, TD-OCT evaluates a small macular area, whereas SD-OCT images al‐ most the entire macular region.

#### **6.3. OCT imaging of CNV**

OCT is more reliable than biomicroscopy in assessing the macular thickness and small neurosensory and RPE

OCT is less precise in evaluating the geographic extent of fluid within the macula, as compared to FA. Due to the cross-sectional imaging, OCT allows the localization of a CNV in relationship with the RPE and the

140 Age-Related Macular Degeneration - Etiology, Diagnosis and Management - A Glance at the Future

OCT is superior to FA in identifying CNV membranes that are obscured by pooling of dye or by tiny retinal

**Table 3.** Place of OCT in the ophthalmic evaluation of the AMD patients – summary for the clinician

OCT is more reliable than FA in identifying the intraretinal and subretinal fluid, as on FA the fluid in the inner retina

OCT is very useful in AMD monitoring and decision-making after treatment: if fluid persists, re-treatment is indicated.

In AMD, the most important clinical parameter is the central macular thickness. OCT is the most precise method to measure retinal thickness in vivo. However, OCT measure‐ ments cannot be correlated exactly to the histopathologic ones, because OCT signals are directly determined by the optical properties of tissues. Therefore, structures that stain strongly on the histopathological specimens do not necessarily appear as intense OCT signals. It has been demonstrated that there are differences in the retinal thickness measurements between OCT models, possibly explained by the higher axial and trans‐ verse resolution of the newer devices. For instance, a comparison was made between Cirrus and Stratus OCT devices in measuring the macular thickness [19]. Firstly, the definition of the retinal boundaries used by the automated segmentation algorithms dif‐ fers between devices [19]. According to the manufacturer, the Stratus OCT program measures between the nerve fiber layer and the inner boundary of the RPE complex, though it has been reported that Stratus OCT has two outer reference lines: one at the junction between the inner/outer segment of the photoreceptor cells and the other at the inner boundary of the RPE. The Cirrus OCT program measures the retinal thickness be‐ tween the nerve fiber layer and the outer band of the RPE. In consequence, the Cirrus outer reference band is deeper than the first mentioned Stratus external band and is closer to the second mentioned one. The correlation of thickness measurements between the two devices is modest, as the Cirrus OCT provides greater measurement depth. The practical implications are targeted towards the clinical practice (the patients participat‐ ing in clinical trials may not interchange between Stratus and Cirrus OCT systems, pa‐ tients transiting from one practice to another should have the tests done with the same OCT model) and the manufacturer (upgradation of Stratus OCT software). Secondly and more importantly, the TD-OCT calculates the retinal thickness based on 6 radial line scans, whereas SD-OCT uses data of 3D scan with 128-200 scans over the same area [19]. Thus, TD-OCT evaluates a small macular area, whereas SD-OCT images al‐

detachments.

neurosensory retina.

haemorrhages.

can mask the fluid in the outer retina.

Cystoid macular edema is strongly associated with the classic CNV.

**6.2. OCT measurement of macular thickness**

most the entire macular region.

In neovascular AMD, the retina is invaded by new vessels originating in the choroidal ves‐ sels. According to the relationship of these new vessels with the retinal architecture, wet AMD presents in two forms: classic CNV and occult CNV. The histopathological studies proved that in classic CNV the new vessels penetrate Bruch's membrane, the RPE and the neural retina, whereas in occult CNV they are located between the RPE and Bruch's mem‐ brane, with subsequent loss of RPE barrier function. In classic CNV the RPE is elevated by exudates, blood and lipids located in the subretinal space and having the origin in the new vessels. The occult CNV can be further divided in two forms: with or without serous pig‐ ment epithelial detachment [20] (Table 4). Cystoid macular edema was statistically strongly correlated with the classic form of choroidal neovascularization, whereas the absence of cys‐ toid macular edema was statistically strongly correlated with the occult choroidal neovascu‐ lar membranes.


**Table 4.** Summary of CNV types – correlation of the histopathological and clinical findings

Occult CNV were described initially on fluorescein angiography (FA) and then on indocya‐ nine green angiography (ICGA) that detected them more accurately, mainly if Scanning La‐ ser Ophthalmoscopy (SLO) was also used. In the recent years, OCT proved its usefulness in defining the features of occult CNV. The main OCT finding that defines occult CNV is the RPE elevation that is separated from the underlying choroidal plane. The cavity formed by the RPE elevation is most frequently fibrovascular and therefore coloured in green, but it can also be serous and then appears optically empty. The RPE elevation is poorly delineated and its extent is variable according to the stage of the lesion. In occult CNV, the RPE eleva‐ tion can be associated with other OCT signs: modifications of the RPE band (hyperreflectivi‐ ty, fragmentations, thickening, thinning), subretinal and intraretinal accumulation of fluid, vitreomacular traction syndrome [21].

#### **6.4. OCT in the evaluation of the therapeutical response to photodynamic therapy in wet AMD**

OCT helped to better describe the response to treatment in wet AMD. For instance, the response to photodynamic therapy takes place in 5 stages: in the first stage, there is a mild fluid accumulation that corresponds to an acute inflammatory reaction after PDT. Approximately 4 weeks after the first treatment, if there is fluid accumulation, retreat‐ ment is suggested. Typically, the fluid accumulates in the subretinal space, causing the detachment of the neurosensory retina. Cystoid macular edema is evident in the penul‐ timate stage, approximately 5 months after PDT and it is associated with important subretinal fibrosis on OCT. In the last stage, there is complete resolution of retinal flu‐ id, concomitant with subretinal fibrosis and retinal atrophy. In conclusion, OCT has a significant impact on the therapeutic approach in AMD: the presence of subretinal fluid proves an active CNV and further therapy is indicated, the presence of fibrosis is asso‐ ciated with cystoid macular edema that has no benefit from therapy as compared to its natural evolution [20].

**6.7. Choroidal thickness measurements**

**6.8. External retinal cysts**

pearance of the external retinal layers [3].

**6.9. OCT in dry AMD**

Choroid is a very important structure for AMD, because abnormalities at the level of the choroidal circulation seem to be the most significant factor involved in the development of this disease. The use of the newest OCT software enables the measurement of choroidal thickness, but only few studies evaluated it in AMD. So far, it has been proved that the cho‐ roidal thickness is variable among patients with AMD. In the group of patients with thicker than normal choroid it is difficult to include them in one of the three following cathegories: a variant of normal, a subset of AMD or a different entity. An overall concluison is that the patients with wet AMD displayed thinner choroids than the ones with dry AMD. These findings postulate that the continuing thinning of the choroid might be a factor indicating the risk of progression towards wet AMD. Therefore, the OCT evaluation of the choroidal thickness could be a valuable tool in identifying the patients at risk to develop the wet form of AMD, thus allowing the early diagnosis and therapy. The thinner than normal choroid induces ischemia at the level of RPE, stimulating the production of VEGF and subsequent proliferation of new vessels. Until now, OCT studies could not establish a correlation be‐ tween the choroidal thickness and parameters with practical importance: number of intravi‐

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The new OCT imaging techniques allowed to identify the external retinal cysts that differ from the ones in cystoid macular edema and therefore to avoid the useless treatment. They are not perfectly understood yet, but the intravitreal anti-VEGF injections don't seem to in‐ fluence their evolution. The origin of the external retinal cysts is explained by two theories: inflammatory and mechanical. The inflammatory theory postulates that following photore‐ ceptor and pigment epithelial cells degeneration induced by intravitreal injections of anti-VEGF agents, specific macrophages appear in order to digest the cellular debris. It seems that the external retinal cysts are giant activated macrophages. This theory is sustained by the localization of these cysts in areas of high concentrations of oxidized lipoproteins: in front of the ancient fibro-vascular lesions and of the extended regions of retinal and pigment epithelial atrophy. In accordance with the mechanical theory, the external retinal cysts are rolled photoreceptor cells. During the process of retinal degeneration, the tight junctions be‐ tween the external segments of the photoreceptor cells disappear and they subsequently form tube-like structures in the external retina. OCT findings exclude the mechanical theory, as the tube-like structures were never identified in AMD, whereas the segmentation OCT techniques proved that the "tubes" correspond to plies of the pigment epithelium and not to rolled photoreceptors. The OCT identification of the external retinal cysts carry an unfavora‐ ble prognosis as they are associated with ancient degenerative lesions and with the disap‐

In dry AMD there is atrophy of the choroid with subsequent degeneration of RPE and invo‐ lution of the photoreceptor and external retinal layers. However, even if the RPE becomes

treal anti-VEGF injections, duration of the disease, visual acuity [27].

#### **6.5. OCT imaging of Pigment Epithelial Detachments (PEDs)**

In the context of the chorio-retinal diseases, AMD is the condition in which PEDs are the most frequently identified. As hypothesized by Gass, PEDs occur in AMD by two mecha‐ nisms: serous exudation from hyperpermeable vessels of the choriocapillaris through an in‐ tact Bruch's membrane or neovascular ingrowth with subsequent exudation from the new vessels directly in the subretinal space [22]. Using a TD-OCT device, which was not able to visualize within the PED, Coscas was the first to observe that the presence of a layer of tis‐ sue behind the RPE in PEDs is associated with occult CNV. The new devices allow the de‐ scription of the PEDs content: the dark regions within them are not attributable to the low sensitivity of the imaging technique, but to the hyporeflectivity of the region itself [22]. Be‐ fore the OCT era, PEDs were assessed manually or automatically according to their areas. However, PEDs can have similar areas but very different volumes, their three-dimensional evaluation being therefore very important. Cirrus SD-OCT system can be used in order to measure the area and volume of PEDs with the help of an algorithm similar to the one re‐ ported for the measurement of drusen and that proved to be highly reproducible [23]. The PEDs usually indicate the presence of CNV and are associated with poorer visual outcome. Therefore, their identification carries a prognostic value [22,23].

#### **6.6. OCT imaging of vitreomacular adhesions**

Although AMD involves primarily the outer retinal layers, is was suggested by several au‐ thors that vitreous may play a role in AMD pathogenesis and/or progression [24]. There is clinical evidence that vitreomacular adhesions may play a role in AMD development. It was proved that the prevalence of PVD was significantly lower in patients with AMD as com‐ pared with healthy subjects [25]. In patients with partial PVD, the region of vitreomacular adhesion corresponded to the area of subretinal neovascularization [26]. Also, the incidence of persistent vitreomacular adhesion was significantly higher in eyes with wet AMD as com‐ pared to those with dry AMD and controls. Vitreous was also demonstrated to be important in inducing PEDs. If future prospective studies will confirm these findings, it seems appro‐ priate to use OCT in order to assess the vitreomacular relationship in AMD patients. Subse‐ quently, the OCT findings could guide the prevention of wet AMD, by establishing the indication for vitrectomy or pharmacologic vitreolysis [24,25,26].

#### **6.7. Choroidal thickness measurements**

detachment of the neurosensory retina. Cystoid macular edema is evident in the penul‐ timate stage, approximately 5 months after PDT and it is associated with important subretinal fibrosis on OCT. In the last stage, there is complete resolution of retinal flu‐ id, concomitant with subretinal fibrosis and retinal atrophy. In conclusion, OCT has a significant impact on the therapeutic approach in AMD: the presence of subretinal fluid proves an active CNV and further therapy is indicated, the presence of fibrosis is asso‐ ciated with cystoid macular edema that has no benefit from therapy as compared to its

142 Age-Related Macular Degeneration - Etiology, Diagnosis and Management - A Glance at the Future

In the context of the chorio-retinal diseases, AMD is the condition in which PEDs are the most frequently identified. As hypothesized by Gass, PEDs occur in AMD by two mecha‐ nisms: serous exudation from hyperpermeable vessels of the choriocapillaris through an in‐ tact Bruch's membrane or neovascular ingrowth with subsequent exudation from the new vessels directly in the subretinal space [22]. Using a TD-OCT device, which was not able to visualize within the PED, Coscas was the first to observe that the presence of a layer of tis‐ sue behind the RPE in PEDs is associated with occult CNV. The new devices allow the de‐ scription of the PEDs content: the dark regions within them are not attributable to the low sensitivity of the imaging technique, but to the hyporeflectivity of the region itself [22]. Be‐ fore the OCT era, PEDs were assessed manually or automatically according to their areas. However, PEDs can have similar areas but very different volumes, their three-dimensional evaluation being therefore very important. Cirrus SD-OCT system can be used in order to measure the area and volume of PEDs with the help of an algorithm similar to the one re‐ ported for the measurement of drusen and that proved to be highly reproducible [23]. The PEDs usually indicate the presence of CNV and are associated with poorer visual outcome.

Although AMD involves primarily the outer retinal layers, is was suggested by several au‐ thors that vitreous may play a role in AMD pathogenesis and/or progression [24]. There is clinical evidence that vitreomacular adhesions may play a role in AMD development. It was proved that the prevalence of PVD was significantly lower in patients with AMD as com‐ pared with healthy subjects [25]. In patients with partial PVD, the region of vitreomacular adhesion corresponded to the area of subretinal neovascularization [26]. Also, the incidence of persistent vitreomacular adhesion was significantly higher in eyes with wet AMD as com‐ pared to those with dry AMD and controls. Vitreous was also demonstrated to be important in inducing PEDs. If future prospective studies will confirm these findings, it seems appro‐ priate to use OCT in order to assess the vitreomacular relationship in AMD patients. Subse‐ quently, the OCT findings could guide the prevention of wet AMD, by establishing the

**6.5. OCT imaging of Pigment Epithelial Detachments (PEDs)**

Therefore, their identification carries a prognostic value [22,23].

indication for vitrectomy or pharmacologic vitreolysis [24,25,26].

**6.6. OCT imaging of vitreomacular adhesions**

natural evolution [20].

Choroid is a very important structure for AMD, because abnormalities at the level of the choroidal circulation seem to be the most significant factor involved in the development of this disease. The use of the newest OCT software enables the measurement of choroidal thickness, but only few studies evaluated it in AMD. So far, it has been proved that the cho‐ roidal thickness is variable among patients with AMD. In the group of patients with thicker than normal choroid it is difficult to include them in one of the three following cathegories: a variant of normal, a subset of AMD or a different entity. An overall concluison is that the patients with wet AMD displayed thinner choroids than the ones with dry AMD. These findings postulate that the continuing thinning of the choroid might be a factor indicating the risk of progression towards wet AMD. Therefore, the OCT evaluation of the choroidal thickness could be a valuable tool in identifying the patients at risk to develop the wet form of AMD, thus allowing the early diagnosis and therapy. The thinner than normal choroid induces ischemia at the level of RPE, stimulating the production of VEGF and subsequent proliferation of new vessels. Until now, OCT studies could not establish a correlation be‐ tween the choroidal thickness and parameters with practical importance: number of intravi‐ treal anti-VEGF injections, duration of the disease, visual acuity [27].

#### **6.8. External retinal cysts**

The new OCT imaging techniques allowed to identify the external retinal cysts that differ from the ones in cystoid macular edema and therefore to avoid the useless treatment. They are not perfectly understood yet, but the intravitreal anti-VEGF injections don't seem to in‐ fluence their evolution. The origin of the external retinal cysts is explained by two theories: inflammatory and mechanical. The inflammatory theory postulates that following photore‐ ceptor and pigment epithelial cells degeneration induced by intravitreal injections of anti-VEGF agents, specific macrophages appear in order to digest the cellular debris. It seems that the external retinal cysts are giant activated macrophages. This theory is sustained by the localization of these cysts in areas of high concentrations of oxidized lipoproteins: in front of the ancient fibro-vascular lesions and of the extended regions of retinal and pigment epithelial atrophy. In accordance with the mechanical theory, the external retinal cysts are rolled photoreceptor cells. During the process of retinal degeneration, the tight junctions be‐ tween the external segments of the photoreceptor cells disappear and they subsequently form tube-like structures in the external retina. OCT findings exclude the mechanical theory, as the tube-like structures were never identified in AMD, whereas the segmentation OCT techniques proved that the "tubes" correspond to plies of the pigment epithelium and not to rolled photoreceptors. The OCT identification of the external retinal cysts carry an unfavora‐ ble prognosis as they are associated with ancient degenerative lesions and with the disap‐ pearance of the external retinal layers [3].

#### **6.9. OCT in dry AMD**

In dry AMD there is atrophy of the choroid with subsequent degeneration of RPE and invo‐ lution of the photoreceptor and external retinal layers. However, even if the RPE becomes atrophic, it preserves the barrier function, keeping the macular region dry [20]. The current OCT systems allow the identification of drusen. The small and intermediary size ones ap‐ pear as discrete elevations of the RPE with variable reflectivity, according to the underlying material. In the large drusen (or so-called drusenoid PEDs) the RPE displays greater, often dome-shaped elevations separated from the Bruch membrane by a hypo or medium reflec‐ tive material. On OCT images drusen are often accompanied by modifications in the neuro‐ sensory retina, translated by the thinning of the outer nuclear layer and disruption at the level of the external limiting membrane and of the inner segment (IS)-outer segment (OS) junctions. These observations are in agreement with the histopathological ones that demon‐ strated the loss of photoreceptor cells in patients with drusen [28]. Geographic atrophy (GA) appears on OCT as sharply demarcated areas of choroidal hyperreflectivity due to the loss of RPE. If retinal atrophy is associated, thinning or loss of the outer nuclear layer, absence of the external limitting membrane and of the IS-OS junctions are seen. In the areas of GA, is‐ lands of preserved retina may be identified, as well as regressing drusenoid materials ap‐ pearing as hyperreflective plaques at the RPE band. In the GA in the inner nuclear layer may be identified small cystic-like spaces in the absence of any macular edema [28]. The evaluation of GA in terms of size, location and rate of progression is crucial in assessing the visual prognosis of the patients. An important finding that identifies the rapidly progressive cases is the autofluorescence surrounding the GA areas. OCT also revealed in the junctional zones of GA that the outer plexiform layer approaches the Bruch membrane suggesting that photoreceptor loss extends beyond the limits of the lesion. OCT reveals dynamic changes in the junctional zones of GA: pigment migration, variation in drusen height. In conclusion, OCT examination in dry AMD is important in two main directions: it provides insights in the disease pathogenesis and it allows the prediction of visual outcome [28].

extension of subretinal or intraretinal fluid objectivized on SD-OCT or even TD-OCT im‐ ages. It was postulated that minimal fluid on the OCT images might not represent leakage from a newly formed CNV, but failure of liquid resolution by the PRE. Therefore, some au‐ thors recommend retreatment by intravitreal anti-VEGF injections only if the presence of fluid on SD-OCT is associated with leakage on FA. However, since SD-OCT is more reliable in detecting extravasated fluid, retreatment based on SD-OCT parameters should be more effective, especially that the pharmacologic therapies act by reducing leakage rather than by an antiproliferative effect [29]. The OCT technology allows new diagnostic criteria for AMD and the decision-making process and AMD monitoring without the need to subject the pa‐ tient to fluorescein angiography [8]. The ultrahigh-resolution OCT uses a titanium-sapphire laser light source that delivers image resolutions of 3 μm [8]. This is particularly useful in neovascular AMD for the precise evaluation of sub-RPE and sub-foveal choroidal neovascu‐ lar membranes [8]. On OCT basis, Hee et al. proposed a simple classiffcation scheme of exu‐ dative AMD into three categories which does not always correlate with the FA aspects: welldefined CNV, poorly-defined CNV, fibrovascular pigment epithelial detachment. In poorlydefined CNV, the choroidal reflectivity is diffusely increased and is associated with intraretinal or subretinal fluid accummulation that appears hyporeflective. The presence of the fluid or the small disruptions at the level of the RPE or choriocapillaris differentiate the poorly-defined CNV from the RPE atrophy that is translated on OCT as increased choroidal reflectivity as well. The introduction of OCT in the clinical practice was followed by the modification of the classification schemes based on FA. Thus well-defined CNVs or fibro‐ vascular pigment epithelium detachments appear as precisely demarcated boundaries on OCT, whereas on FA sometimes they were classified as occult choroidal neovascular mem‐ branes. Poorly-defined CNVs correspond to angiographically occult CNVs in most instan‐ ces. The emerging conclusion of these practical observations is that OCT provides anatomical details that are not evident on FA. The most important consequence is the opti‐ mization at the therapeutic level, as the approaches in angiographically classic and occult

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We used the Stratus OCT device (Carl Zeiss Meditech) with the fast macular map scan pro‐ tocol that consists in 6 radial scans oriented 30 degrees from one another, each having a 2 mm axial depth and 6-mm transverse length. Each image had 10 μm axial and 20 μm transverse resolutions in tissue with a maximum scan velocity of 400 axial scans per second. Figures 1a and b depict the case of a patient with wet AMD with significantly increased macular thickness (central foveal thickness of 427 μm). Macular edema is provoqued not on‐ ly by the CNV visible on the cross-sectional images of the retina, but also by an increased vitreo-macular adhesion. The relatively long evolution of the disease is suggested by the modifications in the internal retinal layers, with hyporeflective cysts within their structure. The OCT aspect confirms the theory that the maximal vitreo-macular adhesion is located in

CNVs are different [8,29].

**7. Stratus OCT in clinical practice**

front of the subretinal neovascular membrane.

#### **6.10. OCT versus angiography in AMD**

The advantages of OCT over fluorescein angiography (FA) are represented by: better struc‐ tural identification of CNV, identification of a CNV masked by the pooling of dye or by thin haemorrhages. On FA, in order to suspect the retinal edema the source of leakage has to be active, whereas on OCT even the minimal edema can be objectivized, no matter if the source of leakage is active or not. Cystoid macular edema in exudative AMD is difficult to be vi‐ zualized on FA because of the leakage that obscures the accummulation of fluid in the inner retina. Based on the OCT findings, the prevalence of cystoid macular edema in the cases of subfoveal CNV due to AMD in a retrospective study was estimated to be arround 46%. It has been demonstrated that during all the phases the ICGA substantially underestimated the size of the neovascular complex in comparison to SD-OCT. This could be explained by the high molecular weight and affinity of indocyanine green for the albumin molecules that prevented its even distribution through the entire lesion. Well defined hyperfluorescence during the early phase of FA defining the neovascular complex also underestimated the size of the lesion measured with SD-OCT. On the other hand, despite the SD-OCT capabilities of delivering high resolution images, the components of a fibrovascular complex may repre‐ sent other subretinal material, particularly of inflammatory origin. Another important obser‐ vation refers to the extent of leakage during the late phase of FA that did not reach the

extension of subretinal or intraretinal fluid objectivized on SD-OCT or even TD-OCT im‐ ages. It was postulated that minimal fluid on the OCT images might not represent leakage from a newly formed CNV, but failure of liquid resolution by the PRE. Therefore, some au‐ thors recommend retreatment by intravitreal anti-VEGF injections only if the presence of fluid on SD-OCT is associated with leakage on FA. However, since SD-OCT is more reliable in detecting extravasated fluid, retreatment based on SD-OCT parameters should be more effective, especially that the pharmacologic therapies act by reducing leakage rather than by an antiproliferative effect [29]. The OCT technology allows new diagnostic criteria for AMD and the decision-making process and AMD monitoring without the need to subject the pa‐ tient to fluorescein angiography [8]. The ultrahigh-resolution OCT uses a titanium-sapphire laser light source that delivers image resolutions of 3 μm [8]. This is particularly useful in neovascular AMD for the precise evaluation of sub-RPE and sub-foveal choroidal neovascu‐ lar membranes [8]. On OCT basis, Hee et al. proposed a simple classiffcation scheme of exu‐ dative AMD into three categories which does not always correlate with the FA aspects: welldefined CNV, poorly-defined CNV, fibrovascular pigment epithelial detachment. In poorlydefined CNV, the choroidal reflectivity is diffusely increased and is associated with intraretinal or subretinal fluid accummulation that appears hyporeflective. The presence of the fluid or the small disruptions at the level of the RPE or choriocapillaris differentiate the poorly-defined CNV from the RPE atrophy that is translated on OCT as increased choroidal reflectivity as well. The introduction of OCT in the clinical practice was followed by the modification of the classification schemes based on FA. Thus well-defined CNVs or fibro‐ vascular pigment epithelium detachments appear as precisely demarcated boundaries on OCT, whereas on FA sometimes they were classified as occult choroidal neovascular mem‐ branes. Poorly-defined CNVs correspond to angiographically occult CNVs in most instan‐ ces. The emerging conclusion of these practical observations is that OCT provides anatomical details that are not evident on FA. The most important consequence is the opti‐ mization at the therapeutic level, as the approaches in angiographically classic and occult CNVs are different [8,29].
