Ординатура / Офтальмология / Английские материалы / Textbook of Vitreoretinal Diseases and Surgery_Natarajan, Hussain_2008

Textbook of Vitreoretinal Diseases and Surgery

FIGURE 9-2: (A, top left) Color photograph of the fundus of a patient with peripapillary PCV demonstrates small hemorrhagic pigment epithelial detachment, subretinal hemorrhage, and fluid. The visual acuity was counting fingers. (B, bottom left) ICGA angiography reveals a cluster of actively leaking polypoidal choroidal complexes in the peripapillary area. The patient was treated with photodynamic therapy with verteporpin. (C, top right) Six months after the treatment, color photograph of the fundus demonstrates resolution of the hemorrhagic pigment epithelial detachment, subretinal hemorrhage, and fluid. The visual acuity was 20/60. (D, bottom right, upper) OCT shows retinal pigment epithelial detachment and subretinal fluid before treatment. (E, bottom right, lower) Six months after treatment, OCT shows a significant decrease of retinal pigment epithelial detachment and the resolution of subretinal fluid

Polypoidal Choroidal Vasculopathy

110 eyes with PCV,21 in which the presenting vision was equally distributed across 3 gradients of 0.2, 0.3-0.7, and 0.8, respectively. The mean visual acuity was 20/60.

PCV is characterized clinically by the presence of dilated, choroidal vascular channels ending in orange, bulging, poly-like dilations in the peripapillary region or macular area.24 It is associated with multiple, recurrent, serosanguineous detachments of the RPE and neurosensory retina secondary to leakage and bleeding from these peculiar choroidal vascular lesions.5 The common findings in the fundus are serous macular detachment, subretinal hemorrhage, serous or hemorrhagic RPE detachment, and retinal exudation. Other manifestations included RPE degeneration, subretinal fibrovascular proliferations, and breakthrough vitreous hemorrhage.18,20,21,24 Disiform scarring is uncommon in PCV.18

Studies in Asian populations showed that unilateral involvement was found in most patients (8090%) when they received their initial diagnosis of PCV.8,21,21,23 Many of them demonstrated no evidence of PCV in the fellow eye after more than 10 years’ follow-up. However, in the white population, PCV could present either as a unilateral or bilateral disease.18,19,25,27

PCV lesions can develop at any part of the fundus, although peripapillary lesions were more common in Yannuzzi et al’s series.18 Macular lesions were predominant in most later studies.8,19-21,23,25,27 The lesion can also be located over the mid-peripheral and peripheral fundus.27

DIAGNOSTIC TESTS

The clinical diagnosis of PCV is made on the basis of ophthalmoscopic identification of subretinal reddish-orange spheroidal lesions arising from choroidal vessels. Multiple recurrent serosanguineous RPE or neurosensory retina detachments indicate the possibility of PCV. Definitive diagnosis should be confirmed by the typical features of PCV on ICGA. PCV has two basic choroidal vascular components: a branching network of vessels in the inner choroid and aneurysmal vascular dilations in a polypoidal configuration.6 The polyps could be one or more focal vascular dilatations in the inner choroid. A cluster of grapelike polypoidal vascular dilations may be observed. These characteristic features are shown at the early phase on ICGA.20 The majority of polyps and localized hyperfluorescent lesions with terminal branching are seen within the first minute after injection of ICG dye. In the late phase, the core of the polypoidal lesions may become hypofluorescent because of washout of the dye and show a ring-like staining of the polyps. This might not be seen if there has been active leakage from the polyps.

As most components of PCV are located beneath the RPE, they appear typically as occult CNV on FA.6,7,27,40 However, other fluorescein patterns can also be found. Gomi et al reported 36 eyes with PCV treated with PDT,12 in which the FA pattern was predominantly classic in 8% eyes, minimally classic in 33% eyes, and occult in 58% eyes. PCV may sometimes accompany type 2 (subretinal) CNV, most of which is shown to be classic CNV on FA.46,47 However, leakage from active polypoidal lesions can result in subretinal fibrinous exudation, which may also mimic classic CNV on FA. The visual prognosis of subfoveal type 2 CNV is usually poor. However, it is difficult to differentiate the pure fibrinous exudation from type 2 CNV using FA and optical coherence tomography (OCT). Tamura et al studied 38 PCV eyes with classic CNV patterns on FA.46 They concluded that when subretinal material corresponding to classic CNV is seen in the subfoveal region or is separate from the polypoidal lesions, the eye may actually have type 2 CNV.

OCT is also a useful tool for the diagnosis and evaluation of the response to treatment in eyes

with PCV. Using OCT, Iijima et al and Otsuji et al reported steep dome-like elevations of highly 99

Textbook of Vitreoretinal Diseases and Surgery

reflective RPE layers with underlying moderate reflectivity within the dome consisting of polypoidal lesions of PCV.48-50 Sato et al used third-generation OCT to evaluate 44 eyes with PCV.51 The OCT showed prominent anterior protrusions of the highly reflective RPE in the polypoidal lesions in all eyes. Double reflective layers that consisted of the RPE and another highly reflective layer beneath the RPE (“double-layer sign”) could be seen in area of branching network vessels in 59% of the eyes. These authors suspected that the space within the double-layer sign reflects fluid accumulation between the basement membrane of the RPE and the inner boundary of the Bruch’s membrane/ choriocapillaries complex.

The OCT-ophthalmoscope is a new device that can capture cross-sectional (longitudinal, B-scan) and en face (transverse, C-scan) images of the posterior fundus. The en face OCT could detect round protrusions of the RPE that corresponded to the polypoidal lesions seen on ICGA.52 PEDs were seen as round protrusions of the RPE and were often accompanied by adjacent smaller round protrusions of the RPE, consistent with polypoidal lesions.52,53 The branching vascular networks seen on I CGA often induce slight elevation of the overlying RPE, which typically assumed a geographic shape.52

NATURAL COURSE

The disease often follows a remitting-relapsing course; and clinically, it is associated with chronic, multiple, recurrent serosanguineous detachments of the RPE and neurosensory retina.1-3,5,24 Yannuzzi et al proposed three mechanisms of disease progression.18 The lesion may be enlarged by simple vessel hypertrophy, by conversion of the lesion into the advancing edge of a vascular channel, and by unfolding of a cluster of aneurysmal elements and subsequent transformation into enlarging, vascular, tubular components. New lesions may also develop at a different location within a given eye.

PCV was generally reported to have a better natural course than AMD.7,9,14,24 Patients who have had multiple polypoidal bleeds with spontaneous resolution of the associated detachments can preserve good central vision, particularly when the bleeding was from the peripapillary area.7 Some patients even experience dramatic involution or even autoinfarction of the membrane. However, Uyama et al and Sho et al also observed that one-third to half of patients with PCV may experience severe visual loss (visual acuity of 20/100 or worse).8,21 The causes of severe visual loss could be (1) persist submacular hemorrhage or serous retinal detachment of the macula, which leads to atrophy of the RPE and sensory retina in the macula; or (2) subretinal fibrovascular proliferation, which markedly damages macular function.8,21 Kwok et al stated that the overall visual prognosis for PCV is guarded in the Chinese population. They followed 13 eyes with PCV in a non-laser treated group for 28.2 months (range, 4–60 months).20 The median initial visual acuity was 20/40 (range, 20/25 to 1/60). Only one eye (7.7%) had improvement of two or more Snellen lines, while nine eyes (69.2%) had a gradual decrease of visual acuity of two or more Snellen lines. The mean loss of vision for this group was 3.1 Snellen lines. Ten eyes (76.9%) had a final visual acuity of 20/200 or worse. From our experience, the location of the lesions may be one of the important factors affecting final visual outcome. Extrafoveal PCV was usually associated with a relatively good prognosis. The visual outcome could be expected to be poor if the abnormal choroidal vasculature, retinal exudation, or hemorrhagic detachments involved the subfoveal area. In contrast to the white population, the polypoidal lesions are more likely to located in the macular region than the peripapillary region in Japanese and Chinese populations.1-3,7,8,14,18-21,25-27 This may explain why worse prognoses were reported in the studies from

100 these Asian populations.

Polypoidal Choroidal Vasculopathy

DIFFERENTIAL DIAGNOSIS

The clinical presentations of PCV may resemble those of AMD. A measurable number of elderly patients with findings suggestive of neovascular AMD and serosanguineous macular manifestations will instead have PCV. Yannuzzi et al suggested that PCV is associated with a lower incidence of significant drusen in the fellow eye, occurs more commonly in the peripapillary area, more frequently has large serous PED, and is more prevalent in non-white patients as compared with AMD.7 However, both PCV and AMD can occur simultaneously in the same eye.7 It was also reported that PCV lesions developed after the therapeutic irradiation of neovascular AMD.7

PCV may also mimic central serous chorioretinopathy (CSC) in some patients.26 Yannuzzi et al reported that 13 patients initially thought to have CSC were ultimately given a diagnosis of PCV.26 CSC can be easily differentiated from PCV in most patients; however, in CSC with persistent and/ or recurrent exudation, a myriad of retinal pigment epithelial changes may evolve that make it difficult to differentiate from PCV. In such patients, ICG angiography is useful in differentiating CSC from PCV. Although choroidal vascular hyperpermeability on ICGA is a characteristic feature of CSC, it can also appear in some patients with PCV.54

The differential diagnosis of a reddish orange lesion under the retina includes choroidal hemangioma or metastasis from carcinoid syndrome or, more rarely, renal cell carcinoma, posterior scleritis, and choroidal osteoma.18 ICGA is useful in differentiating PCV from other lesions by showing dilated inner choroidal vessels and polypoidal vascular elements beneath a PED.18

Management

There is no consensus about the best treatment for PCV. Some asymptomatic polyps have been managed conservatively and were noted to resolve spontaneously over time with preservation of good vision.8 Possible treatments for symptomatic PCV include argon laser photocoagulation, photodynamic therapy (PDT), intravitreal anti-VEGF, and surgical removal of fibrovascular membrane with or without macular translocation.9,10,12-17,55

OBSERVATION

Because there is no proven treatment for PCV and the general prognosis is believed to be better than that of AMD, close observation may be a reasonable way to manage those lesions that are located away from the macular region. An Amsler is grid should be provided to patients to monitor any possible progression of lesions into the macular region.

Textbook of Vitreoretinal Diseases and Surgery

with two of them developed disciform scars. However, compared with the untreated group, the latter had a better visual outcome. Kwok et al treated 9 eyes with PCV with laser, and five (56%) of them had stable or improved vision,20 while only four of the 22 untreated eyes (31%) achieved the same result. However, the difference was not statistically significant. Recurrence of polyps subfoveally and subsequent CNV can also occur after laser treatment.23 However, ICGA-guided argon laser photocoagulation is suggested if the PCV is located extrafoveally.

SURGERY

Some authors suggest surgical treatments. Shiraga et al suggested surgical removal of subretinal hemorrhages to minimize iron toxicity and blockage of nutrient diffusion, which could cause irreversible damage to the outer retina.58 However, there was a high incidence (37%) of RPE tears after surgery. Morizane et al reported on 7 eyes with subfoveal PCV that underwent limited macular translocation.59 Five of them improved 2 lines or more on the Snellen chart. However, there is lack of controlled studies to determine the benefit of surgical treatments over the natural history of the disease.

PHOTODYNAMIC THERAPY (PDT)

Recently, an increasing number of reports have shown encouraging results from PDT. PDT with verteporfin is a effective treatment for maintaining or improving visual acuity in patients with symptomatic PCV with macular lesions.13,16,40,41 Stable or improved vision was achieved in 81% to 95% of eyes after PDT. Chan et al reported that the use of PDT resulted in the complete absence of leakage on FA and total regression of polypoidal lesions on ICGA in 91% and 95% of patients, respectively.13 There is no consensus as to whether FA or ICG should be used to guide the PDT treatment in eyes with PCV, although most studies adopted ICGA-guided treatment.10,12,13 The size of the laser spot was chosen to cover the polyps and the surrounding abnormally dilated choroidal vessels shown on ICGA plus an extra margin of 1000 μm. In contrast to the treatment of AMD, the adjacent PED or hemorrhage in eyes with PCV was not included with the lesion. The number of PDT sessions necessary to treat PCV was less than that for typical AMD.13,16,40-43 Gomi et al showed that PDT is more efficacious for PCV than for AMD in Japanese patients.12 However, recurrent or new PCV lesions may develop after successful treatment.12 Subretinal hemorrhage is another common complication after treatment with PDT in eyes with PCV; a few patients may have severe visual loss because of extensive subretinal hemorrhages and vitreous hemorrhage.13,60,61 Hirame et al61 reported that postoperative subretinal hemorrhage was seen in 30.8% of eyes after treatment with PDT for PCV. Most of the hemorrhage was seen within 1 month after PDT, but some might occur after more than 3 months. Lesions needing larger sized spots of laser irradiation might have such hemorrhageic complications. The subretinal hemorrhage was absorbed without treatment in most of the eyes; however, vitreous hemorrhage in some eyes might require pars plana vitrectomy. If the location of the lesion is subfoveal or very close to the fovea, PDT may be the best current choice for treating the patient.

ANTI-VEGF THERAPY

VEGF concentrations in the aqueous humor were markedly increased in patients with PCV when compared with normal controls.39 The specimens from the eyes with PCV also showed strong 102 expression of VEGF in the vascular endothelial cells and the RPE cells.15,62 These data support the

Polypoidal Choroidal Vasculopathy

potential rationale for the use of anti-VEGF treatment in PCV. A few uncontrolled studies using intravitreal bevacizumab in PCV eyes have been reported recently. The preliminary data showed that intravitreal anti-VEGE may stabilize the vision and reduce subretinal fluid; however, it seems ineffective for resolving the polypoidal lesions. Further studies are required to elucidate the long term efficacy of different kinds of anti-VEGF therapies.

COMBINATION THERAPY

Combination therapy using agents with different mechanisms may, theoretically, provide a synergic effect in the treatment. Possible combinations could consist any of the anti-VEGF, intravitreal steroid, PDT, and laser photocoagulation therapies. The benefits of different combination therapies are worthy of further study.

OTHER TREATMENTS

Vedantham et al reported a case of PCV that was successfully treated with transpupillary thermotherapy (TTT).66 However, Mitamura et al showed that TTT was less effective and required more treatments than PDT in patients with PCV.14 Vitreous hemorrhage developed in 2 of the 11 eyes treated with TTT.

Conclusion

In summary, PCV is a distinct disease characterized by recurrent serous hemorrhage or detachments of the RPE and neurosensory retina. ICGA is used to confirm the diagnosis by showing the typical branching network of vessels in the inner choroid and aneurysmal vascular dilations in a polypoidal configuration. The incidence and demographic characteristics vary among patients with different ethnicities. Although the visual prognosis is believed to be better than AMD, half of the patient may suffer from severe visual loss because of atrophy of the RPE and sensory retina in the macula or subretinal fibrovascular proliferation. Possible treatments include laser photocoagulation, anti-VEGF therapy, PDT, and surgical removal of the subretinal fibrovascular membrane with or without macular translocation. Recent studies of treatment using PDT showed promising visual outcomes. In addition, a trend towards combination therapy may develop in the near future.

References

1.Stern RM, Zakov ZN, Zegarra H, Gutman FA. Multiple recurrent serosanguineous retinal pigment epithelial detachments in black women. Am J Ophthalmol 1985;100:560-9.

2.Perkovich BT, Zakov ZN, Berlin LA, Weidenthal D, Avins LR. An update on multiple recurrent serosanguineous retinal pigment epithelial detachments in black women. Retina 1990;10:18-26.

3.Kleiner RC, Brucker AJ, Johnston RL. The posterior uveal bleeding syndrome. Retina 1990;10:9-17.

4.Blumenkranz MS, Kaplan HJ, Clarkson JG, Culbertson WW, Williams GA, Kleiner RC, Meissner RH. Acute multifocal hemorrhagic retinal vasculitis. Ophthalmology 1988;95:1663-72.

5.YannuzziLA,SorensonJ,SpaideRF,LipsonB.Idiopathicpolypoidalchoroidalvasculopathy(IPCV).Retina1990;10:1-8.

6.Spaide RF, Yannuzzi LA, Slakter JS, Sorenson J, Orlach DA. Indocyanine green videoangiography of idiopathic polypoidal choroidal vasculopathy. Retina 1995;15:100-10.

7.Yannuzzi LA, Ciardella A, Spaide RF, Rabb M, Freund KB, Orlock DA. The expanding clinical spectrum of idiopathic polypoidal choroidal vasculopathy. Arch Ophthalmol 1997;115:478-85.