Association of Lesion Size and Visual Prognosis to Polypoidal Choroidal Vasculopathy




Purpose


To investigate the progression of vascular lesions of polypoidal choroidal vasculopathy (PCV) as viewed with indocyanine green angiography and the visual prognosis of these eyes.


Design


Retrospective case study.


Methods


We reviewed retrospectively the medical records of 88 consecutive patients (88 eyes) with PCV who had been examined with indocyanine green angiography for more than 2 years.


Results


Depending on the initial area of the vascular lesion, eyes were divided into smaller PCV (baseline area of lesion being < 1 disc area [DA], n = 22) and larger PCV (baseline area of lesion being ≥ 1 DA, n = 66). In larger PCV, the mean area of the lesion progressed significantly from 6.49 ± 8.96 mm 2 to 16.27 ± 14.19 mm 2 ( P < .0001) with marked deterioration of visual acuity ( P < .0001) during follow-up. In contrast, smaller PCV often showed minimal progression of the lesion, only limited exudative change, and the eyes maintained their initially good vision to the final visit. Smaller PCV lesions rarely progressed to extensive PCV lesions. Severe vision-threatening complications (ie, suprachoroidal hemorrhage, vitreous hemorrhage, and tears of the retinal pigment epithelium) were seen only in eyes with larger PCV, and in studying single nucleotide polymorphisms A69S of ARMS2 genes, there was a significant difference in T allele frequency between individuals with smaller PCV and those with larger PCV (20.2% vs 79.8%; P = .0235).


Conclusions


PCV with small vascular lesions shows minimal progression and no vision-threatening complications, and these eyes often maintain good visual acuity for a long time.


Polypoidal choroidal vasculopathy (PCV) first was described as a new clinical entity with a unique form of choroidal vascular abnormality and is characterized by a branching vascular network that terminates in polypoidal lesions seen by indocyanine green angiography. Initially, vascular components of PCV are reported to be seen predominantly in a peripapillary location, but macular PCV and peripheral PCV since have been reported. Yannuzzi and associates expanded the clinical spectrum of this disease and established the current understanding of PCV. Today, macular PCV is more common in Asian populations and seems to be the condition most clinically significant. To date, however, the pathogenesis of PCV is not understood fully, and it is still controversial whether it originates from an abnormality of the inner choroidal vessels or if it is a variant of choroidal neovascularization (CNV).


PCV is accompanied often by recurrent serosanguineous detachments of the retinal pigment epithelium and neurosensory retina, and sometimes results in massive hemorrhagic complications with a sudden loss of vision. Although the extent of visual disturbance in PCV varies, it generally is thought that the visual prognosis of PCV is better than that of exudative age-related macular degeneration (AMD). In a previous report by Uyama and associates, approximately half of the patients with PCV had a favorable visual outcome (better than 20/30) after being followed-up for more than 2 years. In PCV, other vision-threatening complications, such as type 2 CNV, disciform scar, or cystoid macular edema, are reported to be uncommon.


Clinically, the size of the vascular lesions in PCV varies. We sometimes see cases of PCV with a large lesion that show a poor response to the treatment and show progression of the lesion, resulting in poor visual prognosis. Tateiwa and associates reported that PCV with a large vascular network that extends beyond the vascular arcade is not uncommon, so we may speculate that vascular lesions of originally small PCV extend over time and result in these large PCV. Clinically, however, we rarely see this type of progression. PCV cases with a small lesion often show minimal exudative change and no progression of the lesion and can maintain good visual function for a long time. Even with an exudative change, small PCV often show a favorable response to treatment. Okubo and associates reported that a reddish-orange nodule alone, or that multiple reddish-orange nodules with a small subretinal hemorrhage, is a sign of a potentially benign clinical course, so the clinical course of small and large PCV may be different.


To study the progression of vascular lesions in PCV, it is essential to perform repeated indocyanine green angiography, because most vascular lesions of PCV are located beneath the retinal pigment epithelium. So far, however, there is little information on the long-term observation of the vascular components of PCV. In the study described herein, we investigated progression of the vascular lesion of PCV using indocyanine green angiography and visual prognosis of affected eyes. Based on our findings, we report a new classification of PCV and the expected complications and visual prognosis of these 2 types of PCV.


Methods


For this observational case study, we reviewed retrospectively the medical records of 88 consecutive patients (88 eyes) with symptomatic PCV who initially visited the Macula Service of the Department of Ophthalmology at Kyoto University Hospital between January 2004 and October 2007 and who had been examined with both fluorescein and indocyanine green angiography for more than 2 years after their initial visit. When both eyes were diagnosed as having PCV, 1 eye was selected randomly for inclusion in the current study.


The diagnosis of PCV was based on indocyanine green angiography, which shows a branching vascular network that terminates in polypoidal swelling. The polypoidal lesion can be a single polyp or a cluster of multiple polyps. In most cases, the reddish-orange nodule that had been seen by the ophthalmoscopic examination corresponded to the polypoidal lesion. Eyes with other macular abnormalities (ie, AMD, pathologic myopia, idiopathic CNV, presumed ocular histoplasmosis, angioid streaks, and other secondary CNV) were excluded from the current study. Eyes that were treated previously with focal laser photocoagulation, photodynamic therapy (PDT), vitrectomy, radiation therapy, or anti–vascular endothelial growth factor (VEGF) therapy also were excluded from the present study.


At the initial visit, all patients underwent a comprehensive ophthalmologic examination, including measurement of best-corrected visual acuity (VA), determination of intraocular pressure, indirect ophthalmoscopy, slit-lamp biomicroscopy with a contact lens, and optical coherence tomography (OCT). After fundus photographs were obtained, fluorescein and indocyanine green angiography were performed on each patient using a confocal laser scanning system (HRA-2; Heidelberg Engineering, Dossenheim, Germany). In all patients, VA measurement and OCT examination were performed at each follow-up visit. At follow-up visits, angiography was performed if necessary, although all patients in the current study were examined with angiography several times during follow-up. In the study described herein, the angiograms obtained at the initial visit were compared with the final angiograms.


In the current study, greatest linear dimension and area of the lesion were determined based on the indocyanine green angiography, using the software built into the HRA-2 machine. Greatest linear dimension included the entire PCV vascular lesion, including polypoidal lesion, branching vascular network vessels, and any type 2 CNV. The area of the vascular lesion was measured manually with the software that came with the HRA-2. The pigment epithelial detachment, without underlying vascular components, was not included in measurement of the greatest linear dimension and area of the lesion. In the current study, 1 optic disc area (DA) is equal to 2.54 mm 2 , on the basis of 1 optic disc diameter being equal to 1.8 mm. Based on the area of the lesion at the initial visit, we classified the eyes into either the smaller PCV group (baseline area of lesion < 1 DA) or the larger PCV group (baseline area of lesion ≥ 1 DA) to compare the clinical course of the 2 groups.


We also compared the initial OCT measurement and VA with values obtained at the final visit. To compare the difference in VA, VA measured with a Landolt chart was converted to logarithm of the minimal angle of resolution units. Using OCT images, we obtained 2 measurements (foveal thickness and thickness of the neurosensory retina in the fovea) with a caliper that was built into the software of the OCT machine. Foveal thickness was defined as the distance between the vitreoretinal interface and the retinal pigment epithelium; thickness of the neurosensory retina was defined as the distance between the vitreoretinal interface and the tip the outer segment of the inner and outer segments of the photoreceptors.


We genotyped the major AMD- and PCV-associated single nucleotide polymorphism (SNP), rs10490924 (A69S), of ARMS2. Genomic deoxyribonucleic acid was prepared from leukocytes of peripheral blood using a deoxyribonucleic acid extraction kit (QuickGene-610L; Fujifilm, Minato, Tokyo, Japan). The SNPs were genotyped using Taqman SNP assays with the ABI PRISM 7700 system (Applied Biosystems, Foster City, California, USA) according to the manufacturer’s instructions.


Statistical analysis was performed using software designed for this purpose (StatView version 5.0; SAS Institute, Cary, North Carolina, USA). A P value of less than .05 was considered to be statistically significant.




Results


In the current study, 88 eyes of 88 patients (60 men and 28 women) with PCV, ranging in age from 50 to 86 years (mean ± standard deviation, 70.4 ± 7.5 years), were examined. The follow-up period ranged from 29 to 61 months (mean ± standard deviation, 46.4 ± 8.6 months), and duration from the initial angiogram to the last ranged from 24 to 60 months (mean ± standard deviation, 39.3 ± 9.4 months). All patients were examined with fluorescein and indocyanine green angiography repeatedly during follow-up, ranging from 2 to 11 times (mean ± standard deviation, 4.9 ± 2.0 times). Table 1 shows the characteristics of patients eligible for inclusion in this study. The mean ± standard deviation baseline VA (logarithm of the minimal angle of resolution) was 0.37 ± 0.34. The mean ± standard deviation initial area of the lesion and greatest linear dimension was 7.75 ± 9.78 mm 2 and 3412 ± 1647 μm, respectively. Figure 1 shows the relationship between area of the lesion, greatest linear dimension, foveal thickness, and VA at initial visit and final examination. Initial area of the lesion ( R = 0.801; P < .0001) and initial greatest linear dimension ( R = 0.805; P < .0001) showed a close correlation with final measurements.



TABLE 1

Characteristics of Patients with Polypoidal Choroidal Vasculopathy










































































































































































































Total (n = 88) Smaller Polypoidal Choroidal Vasculopathy (n = 22) Larger Polypoidal Choroidal Vasculopathy (n = 66) P Value
Gender (women/men) 28/60 8/14 20/46 .5971
Age (yrs) 70.4 ± 7.5 68.2 ± 6.9 70.8 ± 7.7 .3257
Hypertension 38 11 27 .4560
Smoking 14 4 10 .7365
Location of lesions (macular/peripapillary/peripheral) 79/8/1 22/0/0 57/8/1 .1881
Duration of symptoms (mos) 8.0 ± 11.9 7.0 ± 9.5 8.3 ± 12.6 .6484
Initial conditions
Best-corrected visual acuity (logMAR) 0.37 ± 0.34 0.24 ± 0.29 0.42 ± 0.35 .0383
Area of lesion (mm 2 ) 7.75 ± 9.78 1.68 ± 0.53 9.79 ± 10.55 .0006
Greatest linear dimension (μm) 3412 ± 1647 1901 ± 464 3915 ± 1591 <.0001
Foveal thickness (μm) 403.5 ± 189.9 377.6 ± 175.4 412.2 ± 195.0 .4628
Thickness of neurosensory retina in the fovea (μm) 196.5 ± 83.8 209.1 ± 98.5 192.4 ± 78.6 .4204
Follow-up period (months) 46.4 ± 8.1 44.5 ± 6.7 47.0 ± 8.4 .2020
Treatment
Photodynamic therapy 69 16 53 .3055
(Times of treatments) 1.9 ± 1.1 1.5 ± 0.7 2.1 ± 1.2 .0875
Anti-VEGF therapy 40 6 34 .0480
(Times of treatments) 2.9 ± 2.5 3.8 ± 3.7 2.7 ± 2.2 .3155
Pars plana vitrectomy 4 0 4 .2372
Cataract surgery 8 3 5 .2554
Final conditions
Best-corrected visual acuity (logMAR) 0.62 ± 0.51 0.19 ± 0.33 0.76 ± 0.49 <.0001
Area of lesion (mm 2 ) 13.24 ± 13.47 4.13 ± 3.59 16.27 ± 14.19 .0002
Greatest linear dimension (μm) 4511 ± 2030 2761 ± 900 5095 ± 1967 <.0001
Foveal thickness (μm) 299.7 ± 189.5 235.3 ± 65.1 321.2 ± 211.7 .0651
Thickness of neurosensory retina in the fovea (μm) 197.1 ± 168.1 153.3 ± 38.4 211.7 ± 191.1 .1597
Changes during follow-up
Best-corrected visual acuity (logMAR) 0.24 ± 0.51 −0.05 ± 0.36 0.34 ± 0.51 .0015
Area of lesion (mm 2 ) 5.48 ± 8.13 2.45 ± 3.53 6.49 ± 8.96 .0429
Greatest linear dimension (μm) 1100 ± 1204 860 ± 933 1180 ± 1278 .2838
Foveal thickness (μm) −103.8 ± 221.9 −142.3 ± 163.6 −91.0 ± 237.8 .3500
Thickness of neurosensory retina in the fovea (μm) 0.6 ± 168.0 −55.8 ± 103.3 19.3 ± 181.4 .0691

logMAR = logarithm of the minimal angle of resolution; VEGF = vascular endothelial growth factor; yrs = years.

One disc area (DA) is estimated as 2.54 mm 2 on the basis of the 1 optic disc diameter of 1.8 mm. Based on the area of lesion at the initial visit, polypoidal choroidal vasculopathy (PCV) eyes were divided into smaller PCV (area of lesion, < 1 DA) and larger PCV (area of lesion, ≥ 1 DA).



FIGURE 1


Scattergrams showing area of the lesion, greatest linear dimension, foveal thickness, and visual acuity (VA) in eyes with polypoidal choroidal vasculopathy (PCV) obtained at initial and final examinations. (Top left) Initial area is correlated significantly with final area of the lesion ( R = 0.801; P < .0001). (Top right) Initial greatest linear dimension is correlated significantly with final greatest linear dimension ( R = 0.805; P < .0001). (Bottom left) Correlations between initial and final foveal thickness ( R = 0.316; P = .0025) and (Bottom right) initial and final VA ( R = 0.355, P = .0006). VA measured with a Landolt chart was converted to logarithm of the minimal angle of resolution (logMAR) units.


PCV vascular lesion at the initial visit varied in size, ranging from 0.64 to 63.82 mm 2 . Depending on the initial area of the lesion, we divided the eyes with PCV into 2 groups—the smaller PCV group (baseline area of lesion, < 1 DA; n = 22) and the larger PCV group (baseline area of lesion, ≥ 1 DA; n = 66; Figure 2 ). The mean area ± standard deviation of the lesion initially was 1.68 ± 0.53 mm 2 in the smaller PCV group and 9.79 ± 10.55 mm 2 in the larger PCV group. There were no significant differences in gender, age, or duration of symptoms between groups ( P = .5971, P = .3257, and P = .6484, respectively). In addition, there were no differences in the foveal thickness ( P = .4628) or thickness of the neurosensory retina in the fovea ( P = .4204) at the initial visit. However, the mean initial VA ± standard deviation was significantly better in eyes with smaller PCV (0.24 ± 0.39) than in eyes with larger PCV (0.42 ± 0.35, P = .0383).




FIGURE 2


Indocyanine green angiograms obtained at the initial visit from eyes with polypoidal choroidal vasculopathy (PCV). All eyes showed the branching vascular network that terminated in a polypoidal lesion, although the lesions varied in size. (Top) Indocyanine green angiograms in the group with smaller PCV. (Bottom) Indocyanine green angiograms in the group with larger PCV.


During the follow-up period, 64 eyes were treated initially with PDT, and 9 were treated initially with anti-VEGF therapy. Despite these treatments, some eyes with larger PCV showed extension of the vascular component with an exudative change. The mean area of the lesion ± standard deviation in larger PCV progressed significantly from 9.79 ± 10.55 mm 2 to 16.27 ± 14.19 mm 2 at the final examination ( P < .0001; Figure 3 ). Furthermore, mean ± standard deviation VA in these eyes deteriorated significantly 0.42 ± 0.35 to 0.76 ± 0.49 at the final examination ( P < .0001). In contrast, eyes with smaller PCV lesions often showed minimal progression of the lesion and limited exudative change, and smaller PCV lesions rarely progressed to extensive PCV lesions ( Figure 4 ). However, even in eyes with smaller PCV, the mean lesion size increased during the follow-up period ( P = .0037). In smaller PCV, mean ± standard deviation change in the area of the lesion and final area of the lesion were 2.45 ± 3.53 mm 2 and 4.13 ± 3.59 mm 2 , respectively, which were significantly less than those of the larger PCV ( P = .0429 and P = .0002, respectively). In addition, eyes with the smaller PCV showed no decrease in VA (−0.05 ± 0.36; P = .5492) and maintained initial VA to the final visit; mean changes in VA were significantly better in smaller PCV than were those in larger PCV ( P = .0015).




FIGURE 3


Images demonstrating progression of the vascular lesion in larger polypoidal choroidal vasculopathy (PCV). (Top left) Fundus photograph at the initial visit showing a reddish orange nodule with a minute pigment epithelial detachment (PED). (Top right) Sectional image obtained with optical coherence tomography (OCT) along with an arrow seen in the fundus photograph showing a small protrusion of the retinal pigment epithelium corresponding to the PED. (Second row left) Fluorescein angiogram obtained at the initial visit showing occult choroidal neovascularization corresponding to a branching vascular network. (Second row right) Indocyanine green angiogram revealing large vascular components of PCV consisting of a polypoidal lesion (arrow) and a branching vascular network (long arrow). The area of the PCV lesion was 5.87 mm 2 . (Third row left) Despite 3 anti–vascular endothelial growth factor treatments, the vascular lesion progressed. Fundus photograph obtained at 33 months after the initial visit showing a large serosanguineous PED. (Third row right) Sectional image obtained by OCT (with the arrow shown in the fundus photograph) showing a steep protrusion of retinal pigment epithelium, which is reflective of the large PED. (Bottom left) Fluorescein angiogram showing occult choroidal neovascularization corresponding to the branching vascular network. (Bottom right) Indocyanine green angiogram showing progression of the polypoidal lesions and extension of the branching vascular network. The area of the PCV lesion increased to 9.40 mm 2 .



FIGURE 4


Images showing no progression of the vascular lesion in smaller polypoidal choroidal vasculopathy (PCV). (Top left) Fundus photograph at the initial visit showing a small reddish orange nodule (arrow); vision was 20/16. (Top middle) Fluorescein angiogram (FA) obtained at the initial visit showing only a hyperfluorescent spot corresponding to the polypoidal lesion. (Top right) Indocyanine green angiogram showing the vascular components of PCV, which consist of a typical polypoidal lesion (arrow) and a branching vascular network (long arrow). The baseline area of the PCV lesion was 1.77 mm 2 . (Second row) Sectional image obtained with optical coherence tomography (OCT) along with the arrow seen in the FA showing a steep protrusion of the retinal pigment epithelium. (Third row left) No treatment was performed. Fundus photograph obtained at 39 months after the initial visit showing a reddish orange nodule with a newly developed serous pigment epithelial detachment; vision was still 20/13. (Third row middle) FA showing a hyperfluorescent spot corresponding to the polypoidal lesion, along with fluorescein pooling in the pigment epithelial detachment. (Third row right) Indocyanine green angiogram revealing no progression of the vascular lesion of PCV. (Bottom) Sectional image obtained with OCT (with the arrow seen on FA) showing protrusion of the retinal pigment epithelium corresponding to the branching network (arrowheads) and steep elevation of the retinal pigment epithelium with moderate inner reflectivity (arrow) corresponding to the polypoidal lesion.


Table 2 shows the ocular manifestations and complications seen during follow-up in eyes with smaller or larger PCV. Of the 88 eyes included, 7 (7.6%) showed suprachoroidal hemorrhage and 8 (8.7%) showed vitreous hemorrhage ( Figure 5 ), all of which were seen in eyes with larger PCV; no eyes with smaller PCV showed severe complications ( P = .1111 and P = .0868). Indeed, in eyes with smaller PCV, even the relatively small amount of subretinal hemorrhage noted (> 1 DA) was seen less frequently than in eyes with larger PCV ( P = .0157). In addition, other ocular manifestations associated with severe visual disturbance were seen more often in eyes with larger PCV. Type 2 CNV, subretinal fibrosis, and cystoid macular edema were seen more frequently in eyes with larger PCV ( P = .0030, P = .0533, and P = .0266). Of the 88 eyes included in this study, 41 (46.6%) showed a serosanguineous pigment epithelial detachment (area, > 1 DA). Again, a pigment epithelial detachment was seen more frequently in eyes with larger PCV than in those with smaller PCV ( P = .0096). Of the 88 eyes of our patients, 8 (8.7%) showed a tear of the retinal pigment epithelium. All of these occurred in eyes with larger PCV; no eyes with smaller PCV showed a tear ( P = .0868).



TABLE 2

Ocular Manifestations and Complications Seen in Eyes with Polypoidal Choroidal Vasculopathy during Follow-up






































































Total (n = 88) Smaller Polypoidal Choroidal Vasculopathy (n = 22) Larger Polypoidal Choroidal Vasculopathy (n = 66) P Value
Suprachoroidal hemorrhage 7 0 7 .1113
Vitreous hemorrhage 8 0 8 .0868
Recurrence 56 11 44 .1620
Type 2 choroidal neovascularization 26 1 25 .0030
Fibrosis 31 4 27 .0533
Serous retinal detachment 81 20 65 .0899
Subretinal hemorrhage (> 1 DA) 55 9 46 .0157
Cystoid macula edema 42 6 36 .0266
Pigment epithelial detachment (> 1 DA) 41 5 36 .0096
Tear of retinal pigment epithelium 8 0 8 .0868

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Jan 16, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Association of Lesion Size and Visual Prognosis to Polypoidal Choroidal Vasculopathy
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