Journal List > J Korean Ophthalmol Soc > v.58(10) > 1010648

Hong, Cho, and Jang: Anatomical Characteristics of End-stage Exudative Age-related Macular Degeneration Refractory to Intravitreal Anti-vascular Endothelial Growth Factor Injection



To analyze the anatomical characteristics on spectraldomain optical coherence tomography (SD-OCT) of patients who are legally blind (less than 20/1,000) due to end-stage exudative age-related macular degeneration (AMD) that does not require intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection.


After anti-VEGF injections (active group), 120 eyes of 103 exudative AMD patients experienced visual acuity improved by at least 2 lines or improvement on SD-OCT. In addition, 55 eyes of 54 end-stage exudative AMD patients who did not respond to treatment or who were legally blind due to foveal scar at the first visit (end-stage group) were evaluated retrospectively. Changes in retinal structures of the 2 groups were analyzed by SD-OCT at the last visit.


The mean age of the end-stage group was about 5 years older than the active group. During the follow-up period, subretinal hemorrhage, intraretinal hemorrhage and retinal pigment epithelium tear occurred more frequently in the end-stage group than in the active group (p < 0.05). Intra-retinal fluids and subretinal fluids were more frequently administered in the active group than in the end-stage group, and thick subretinal hyper-reflective materials (SRHRM), fibrovascular pigment epithelial detachment (PED) and extensive inner segment/outer segment (IS/OS) line disruption were observed in all eyes of the end-stage group. The size and thickness of PED, foveal thickness and SRHRM thickness were significantly larger in the end-stage group than in the active group (p < 0.05). Disciform retinal scars were eventually formed in most of the end-stage group.


In end-stage exudative AMD, the presence of retinal hemorrhage and retinal pigment epithelium tear during fol-low-up, or the findings of thick SRHRM, fibrovascular PED, and extensive IS/OS line disruption on SD-OCT suggest weak expected effect of intravitreal anti-VEGF injection, which can act as a reference for determining the timing of treatment termination.


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Figure 1.
Representative images of morphologic features of spectraldomain optical coherence tomography (SD-OCT) related to age-related macular degeneration. SD-OCT image (A) and corresponding schematic image (B) show multilayered fibrovascular pigment epithelial detachment (f-PED): a fusiform, or spindle-shaped, complex of organized layers of homogenous hyperreflective bands. SD-OCT image (C) and corresponding schematic image (D) demonstrate irregular f-PED with heterogenous, hyper-reflective, dilated, irregular vascular networks. SD-OCT image (E) and corresponding schematic image (F) depict hyporeflective prechoroidal cleft separating the neovascular tissue complex from the underlying choroid and Bruch's membrane.
Figure 2.
Measurement of features of spectraldomain optical coherence tomography related to age-related macular degeneration using Heidelberg engineering software. Representative image of end-stage age-related macular degeneration (A) and corresponding schematic image (B) show thickness (B, blue left right arrow) and size (red left right arrow) of pigment epithelial detachment (PED), thickness of subretinal hyperreflective materials (B, green left right arrow) and size of defect of photoreceptor layer (B, white left right arrow). PED contains choroidal neovascularization (B, red colored lesion) and subretinal hyperreflective materials (B, yellow colored lesion). Macular 1 mm circle thickness and macular volume is measured by using macular 1 mm circle (C, red arrow), macular 6 mm circle (C, black arrow) of Color-coded thickness map.
Figure 3.
Four types of end-stage age-related macular degeneration. Spectral-domain optical coherence tomography (SD-OCT) images. (A) Shows disciform scar with intra-retinal cystoid fluid. SD-OCT image (B) demonstrates disciform scar with destruction of retinal layers. SD-OCT image (C) shows multilayered pigment epithelial detachment (PED) with broad inner segment/outer segment line disruption. SD-OCT image (D) demonstrates thin irregular fibrovascular PED with atrophy of inner retinal layer and inner segment/outer segment line disruptions.
Table 1.
Demographic data of the patients
Characteristics Active (n = 120) End-stage (n = 55) p-value*
Age (years) 69.82 ± 8.24 74.75 ± 6.39 0.037
Sex (male:female) 50:70 19:36 0.408
Mean BCVA (logMAR) 0.53 ± 0.51 2.02 ± 0.18 <0.001
Lens state (n, %)      
 Phakia 79 (65.83) 35 (63.64) 0.864
 Pseudophakia 41 (34.17) 19 (34.54) 0.546
 Aphakia 0 (0) 1 (1.82) 0.314
Retinal events during follow up (n, %)      
 Subretinal hemorrhage 13 (10.74) 19 (34.55) <0.001
 Intra-retinal hemorrhage 9 (7.44) 16 (29.10) <0.001
 RPE tear 8 (6.61) 37 (67.73) <0.001
Received treatment during follow up (n, %)      
 Naïve eyes 0 (0) 4 (7.27) 0.009
 Intravitreal Anti-VEGF injection 94 (78.33) 32 (58.19) 0.010
 PDT 0 (0) 1 (1.81) 0.314
 Intravitreal Anti-VEGF injection + PDT 26 (21.67) 18 (32.73) 0.135

Values are presented as mean ± SD or n (%) unless otherwise indicated.

SD = standard deviation; BCVA = best corrected visual acuity; logMAR = logarithm of the minimum angle of resolution; RPE = retinal pigment epithelium; VEGF = vascular endothelial growth factor; PDT = photodynamic therapy.

* Fisher's exact test, Mann-Whitney U-test.

Table 2.
Comparison of OCT findings of active AMD and end-stage AMD
  Active End-stage p-value*
Subretinal fluid (n, %) 67 (55.83) 17 (30.91) 0.003
Intraretinal cystoid fluid (n, %) 93 (77.50) 34 (61.82) 0.044
Subretinal hyperreflective material (n, %) 42 (35.00) 55 (100.0) <0.001
Prechoroidal cleft (n, %) 5 (4.16) 3 (5.45) 0.708
Atrophic scar (n, %) 2 (1.67) 4 (7.27) 0.079
Disciform scar (n, %) 11 (9.16) 49 (89.09) <0.001
PED (n, %) 108 (90.00) 55 (100) 0.019
 Serous PED 58 (48.33) 0 (0) <0.001
 Drusenoid PED 12 (10.00) 0 (0) 0.019
 Hemorrhagic PED 8 (6.67) 0 (0) 0.057
 Irregular f-PED 28 (23.33) 51 (92.72) <0.001
 Multilayered f-PED 2 (1.67) 4 (7.27) 0.058

Values are presented as n (%) unless otherwise indicated.

OCT = optical coherence tomography; AMD = age-related macular degeneration; PED = pigment epithelial detachment; f-PED = fibrovascular pigment epithelial detachment.

* Fisher's exact test.

Table 3.
Statistical analysis of anatomical characteristics of active AMD and end-stage AMD
  Active End-stage p-value*
PED size (μ m) 2,123.37 ± 1,184.55 3,747.83 ± 1,460.09 0.003
PED thickness (μ m) 179.15 ± 152.27 301.27 ± 160.62 0.001
IS/OS defect size (μ m) 593.21 ± 1,647.36 5,078.27 ± 1,386.17 0.001
FT (μ m) 237.28 ± 57.05 375.80 ± 39.68 0.002
Macular 1 mm circle mean thickness (μ m) 273.94 ± 25.27 400.20 ± 36.86 0.003
Macular volume (mm3) 8.25 ± 0.59 9.35 ± 0.37 0.493
SRHRMT (μ m) 36.26 ± 20.56 197.23 ± 22.69 0.001
FT-SRHRMT (μ m) 219.72 ± 123.83 175.44 ± 48.87 0.134

Values are presented as mean ± SD unless otherwise indicated.

AMD = age-related macular degeneration; SD = standard deviation; PED = pigment epithelial detachment; IS/OS = inner segment/outer segment; FT = foveal thickness; SRHRMT = subretinal hyperreflective material thickness.

* Mann-Whitney U-test.

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