Pigment Epithelial Detachment

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Retinal pigment epithelial detachment
Pigment epithelial detachment
Pigment epithelial detachment. © 2019 American Academy of Ophthalmology [1]


Retinal pigment epithelial detachments (PEDs) are structural splitting within the inner aspect of Bruch’s membrane separating the RPE from the remaining Bruch’s membrane.

Disease Entity

Disease

Retinal pigment epithelial detachments (PEDs) are characterized by separation between the RPE and the inner most aspect of Bruch's membrane. The space created by this separation is occupied by blood, serous exudate, drusenoid material, fibrovascular tissue or a combination.

Background

PEDs in AMD

The classification of PEDs in AMD can be divided based on their contents. Categories include drusenoid, serous, vascularized, or mixed components. Drusenoid PEDs are seen mostly in nonneovascular or dry AMD. Serous PEDs are typically associated with the neovascular or wet form of AMD, but their natural history is relatively more favorable. Vascularized PEDs associated with Type 1 (sub-RPE) neovascularization and wet AMD, in contrast, have a greater risk of vision loss. In eyes with AMD, it is not uncommon to see more than one type of PED.[2]

The development of choroidal neovascularization (CNV) has been associated with long-standing PED. Recognition of its existence is a major concern secondary to its increased risk for severe vision loss.[3]

Etiology

Various Ocular and Systemic Diseases can be associated with PEDs

Ocular Diseases

PEDs are present in several chorioretinal diseases including Vogt-Koyanagi-Harada (VKH) Syndrome, Idiopathic Central Serous Chorioretinopathy (CSC) small multifocal idiopathic PEDs, Polypoidal Choroidal Vasculopathy (PCV), and Exudative/Non-Exudative Age-Related Macular Degeneration (AMD).

Systemic Diseases

PEDs have also been associated with certain systemic conditions including renal (tubulo-interstitial nephritis and uveitis syndrome and type II membranoproliferative glomerulonephritis), Inflammatory (systemic lupus erythematosis, inflammatory bowel disease, sarcoidosis), Infectious (Blastocystis hominis, poststreptococcal syndrome, neurosyphilis), Neoplastic (paraproteinemias including cryoglobulinemia, IgA or IgM gammopathies), Waldenström macroglobulinemia, large cell non–Hodgkin lymphoma (ocular–central nervous system form), choroidal nevi, acute myeloid leukemia, and Iatrogenic reasons (Pamidronate, hemodialysis, organ transplantation.) [2] [4]

Pathophysiology

The retinal pigment epithelium (RPE) monolayer, extending from the optic disk margin uninterrupted through to the ciliary body epithelium, is bounded by the apical surface of the retina and on its basal surface by the collagenous layer of Bruch’s membrane. [3] Proper anatomical apposition between the retina, the RPE, and Bruch’s membrane is crucial for nutritional support of the photoreceptors, retinol metabolism, phagocytosis of the photoreceptors outer segments, and formation of the outer blood-retinal barrier.

The forces maintaining normal adhesion between the RPE and Bruch’s membrane are not well understood. Under normal conditions, there exists a net bulk flow of fluid towards the choroid from the vitreous, with its generation dependent upon hydrostatic and osmotic forces within the two bodies. Both the RPE and the retina produce resistance to this fluid flow. The RPE has greater resistance due to its limited hydraulic conductivity, subsequently, a vector force is generated pushing it against Bruch’s membrane.[5] The attachment of the RPE basement membrane to Bruch’s membrane is possibly supplemented by regions of hemidesmosomes containing fine filaments of laminin, proteoglycans and collagen types IV and V.[6]

Age-related deposition of lipids, such as cholesterol esters, triglycerides, and fatty acids in Bruch's membrane may change its permeability altering retinochoroidal flow.[2] Fluid may accumulate in the sub- RPE space, unable to pass through Bruch membrane, resulting in RPE elevation.

Diagnosis

Diagnosing PEDs relies on careful history and physical exam with further information provided by various imaging modalities.

History

Patients will typically present with painless blurred vision and/or partial vision loss. Others have described a dark shadowing effect or sensation that a curtain has been pulled in front of their vision.

Clinical Exam

Often PEDs will transilluminate if they are filled predominantly with serous fluid when observed at the slit lamp. Pigment figures can also indicate chronicity of disease. Examination reveals a reticulated pattern of increased pigmentation extending radially over the PED, likely due to migration of RPE cells into the outer retinal space however it is unclear whether these carry a prognostic significance.

Drusenoid PED: Drusenoid PEDs appear as well-circumscribed yellow or yellow–white elevations of the RPE that are usually found within the macula. They may have scalloped borders and a slightly irregular surface. It is not uncommon to observe a speckled or stellate pattern of brown or gray pigmentation on their surface.

Serous PED: Serous PED appears as a distinct circular or oval-like detachment of the RPE. Clear or yellowish–orange in color, this dome-shaped elevation of the RPE has a sharply demarcated border.

Vascular PED: Gass reported that a flattened or notched border of the PED is a frequent and important sign of hidden associated CNV.[7] Other biomicroscopic findings suggestive of possible occult CNV association include yellow subretinal and intraretinal exudates that occur typically at the PED margins, subretinal hemorrhages at PED margins, sub-RPE blood which appears darker than subretinal blood with a fluid-level sign, irregular elevation of the PED because of organization in the lesser elevated area, and radial chorioretinal folds surrounding the PED caused by the contraction of Bruch membrane and the CNV.[7]

Diagnostic Imaging

Fundus autofluorescence imaging

Drusenoid PED: Drusenoid PEDs may exhibit decreased FAF but typically they are isofluorescent or hyperautofluorescent.[2] Drusenoid PEDs often show an evenly distributed, modest increase in the FAF signal surrounded by a well defined, hypoautofluorescent halo delineating the entire border of the lesion.

Serous PED: Serous PEDs most often have an even distribution of hyperautofluorescence corresponding to the detachment and are surrounded by a hypoautofluorescent border.

Vascular PED: Fundus autofluorescence imaging of vascularized PEDs has not been evaluated systematically in large series of patients. More work needs to be done to correlate the FAF pattern of PEDs and any associated CNV with findings obtained with FA and SD-OCT.

Fluorescein angiography

Drusenoid PED: Drusenoid PEDs demonstrate faint hyperfluorescence in the early phase that increases throughout the transit stage of the study without late leakage. The correlation of FA findings with SD-OCT and occasionally ICGA may help differentiate drusenoid from vascularized PEDs.

Serous PED: Serous PEDs demonstrate intense early hyperfluorescence and brisk, progressive pooling within the PED in a homogeneous and well-demarcated manner. Late staining of serous PEDs is typical and may make it difficult to differentiate these PEDs from those that are vascularized based on FA alone. In cases where there is suspicion of associated CNV, ICGA is a useful imaging modality. [2]

Vascular PED: From the analysis of fundus photographs of the macula and FA, the Macular Photocoagulation Study identified two main patterns of CNV: classic and occult. Classic CNV is characterized by a well-defined area of early typically lacy hyperfluorescence with progressive leakage in the late stages of the study. An additional fluorescein angiographic pattern of vascularized PEDs is a serous PED with a notch (e.g., kidney bean–shaped PED) or hot spot that may be referred to as a vascularized serous PED.

Indocyanine green angiography

Drusenoid PED: Using a confocal scanning laser ophthalmoscope (SLO) system and ICGA, the content of the drusenoid PED will block the fluorescence emitted from the underlying choroidal vasculature and, therefore, the PED will appear as a homogeneous hypofluorescent lesion during the early phase and remain hypofluorescent throughout the transit.[8]

Serous PED: With an infrared fundus camera, the ICGA reveals only variable, minimal blockage of normal choroidal vessels by the serous PEDs in the late phase. Using a confocal SLO system, the ICGA reveals hypofluorescence in both the early and the late phases of the ICGA study with complete blockage of the normal choroidal vasculature. [9]

Vascular PED:Vascularized PEDs may demonstrate either of two major findings with ICGA analysis. A focal bright area of well-defined hyperfluorescence less than 1 disk diameter in size referred to as a hot spot or focal CNV.

Optical coherence tomography

Drusenoid PED: Drusenoid PEDs usually show a smooth contour of the detached hyperreflective RPE band that may demonstrate an undulating appearance. The material beneath the RPE band typically exhibits a dense homogeneous appearance with moderate or high hyperreflectivity. Drusenoid PEDs are typically not associated with overlying subretinal or intraretinal fluid.

Serous PED: On OCT, serous PEDs appear as well-demarcated, abrupt elevations of the RPE with a homogenously hyporeflective sub-RPE space. Enhanced depth imaging (EDI) OCT is useful to determine whether serous PED is caused by AMD (normal subfoveal choroidal thickness) or by CSC (increased subfoveal choroidal thickness). [10]

Vascular PED: Optical coherence tomography allows better visualization of the exact relationship between neovascular membranes and PEDs. Enhanced depth imaging OCT enables better visualization of the contents of PEDs. Untreated PEDs demonstrate evidence of fibrovascular proliferation, often coursing along the back surface of the detached RPE.

Management

Depending on the etiology of the PED, different treatment modalities have been explored to prevent vision loss.

Treatment

Currently no treatment for serous PED is proven effective, nor are recommendations for treatment guidelines established. Several strategies, however, have being used to treat vascularized PEDs, including laser photocoagulation, photodynamic therapy (PDT), intravitreal steroids and anti-VEGF therapy. The results from the VIP trial indicated that PDT could significantly reduce the risk of moderate and severe vision loss among patients with subfoveal occult CNV.[11] Another treatment modality, described recently by Costa et al as a pilot trial, is photothrombosis at the neovascular ingrowth site using ICG visualization followed by laser application to feeder vessels. Occlusion of the feeder vessel with cessation of leakage, restoration of macular architecture and visual improvement were induced in two patients with CNV associated with PEDs. [12]

Complications

It is well established that the natural history of vascularized PEDs may be complicated by RPE tears. The most important FA feature identified which predicted RPE tears was the uneven filling of the PED, with a hypofluorescent central area that remained dark until the late angiographic frames as well as early hyperfluorescence at the borders of the PED that grew progressively, and sometimes demonstrated a notched edge. [13]

Prognosis

The location of the PED is important in determining prognosis. Patients with extrafoveal PEDs tend to preserve good visual acuity, whereas patients with subfoveal PEDs can have worse visual outcomes. The course of PEDs also varies in CSC versus AMD. Mudvari et al demonstrated with a mean follow-up of 49 months that 65% of PEDs in CSC completely resolved and the other 35% PEDs remained persistent.[14] Retinal pigment epithelium atrophy was evident in 86% of patients over the area of the resolved PED. Others have reported similar findings and noted that patients with a persistent PED had poorer visual outcomes. [15]

The natural course of Type 1 or occult CNV can vary considerably. Type 1 CNV patients can appear relatively asymptomatic and may never experience vision loss despite continued growth of the neovascular lesion.[16] On the other hand, large vascularized or hemorrhagic PEDs are typically associated with significant vision loss. Additionally, Type 1 CNV can erode through the RPE, becoming Type 2 CNV and follow a more aggressive course with more progressive and severe vision loss.

The RPE tear rate in eyes with PED in natural history studies has been noted to be between 10% and 12%,[2] but this rate seems to be accelerated after anti-VEGF therapy (up to 17%).


References

  1. American Academy of Ophthalmology. Pigment epithelial detachment. https://www.aao.org/image/pigment-epithelial-detachment-2 Accessed July 05, 2019.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 Mrejen, S. (2013). Multimodal imaging of pigment epithelial detachment: a guide to evaluation. Retina33(9), 1735-1762.
  3. 3.0 3.1 Zayit-Soudry, S., Moroz, I., & Loewenstein, A. (2007). Retinal pigment epithelial detachment. Survey of ophthalmology52(3), 227-243.
  4. Wolfensberger, Thomas J., and Adnan Tufail. "Systemic disorders associated with detachment of the neurosensory retina and retinal pigment epithelium." Current opinion in ophthalmology 11.6 (2000): 455-461.
  5. Kirchhof, B., & Ryan, S. J. (1993). Differential permeance of retina and retinal pigment epithelium to water: implications for retinal adhesion. International ophthalmology17(1), 19-22.
  6. Marshall, G. E., Konstas, A. G., Reid, G. G., Edwards, J. G., & Lee, W. R. (1994). Collagens in the aged human macula. Graefe's archive for clinical and experimental ophthalmology232(3), 133-140.
  7. 7.0 7.1 Gass, J. D. (1984). Serous retinal pigment epithelial detachment with a notch. A sign of occult choroidal neovascularization. Retina (Philadelphia, Pa.)4(4), 205-220.
  8. Arnold, J. J., Quaranta, M., Soubrane, G., Sarks, S. H., & Coscas, G. (1997). Indocyanine green angiography of drusen. American journal of ophthalmology124(3), 344-356.
  9. Flower, R. W., Csaky, K. G., & Murphy, R. P. (1998). Disparity between fundus camera and scanning laser ophthalmoscope indocyanine green imaging of retinal pigment epithelium detachments. Retina (Philadelphia, Pa.)18(3), 260-268.
  10. Imamura, Y., Fujiwara, T., Margolis, R. O. N., & Spaide, R. F. (2009). Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy. Retina29(10), 1469-1473.
  11. Arnold, J., Barbezetto, I., Birngruber, R., Bressler, N. M., Bressler, S. B., Donati, G., ... & Kaiser, P. K. (2001). Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization-verteporfin in photodynamic therapy report 2. American journal of ophthalmology131(5), 541-560.
  12. Costa, R. A., Rocha, K. M., Calucci, D., Cardillo, J. A., & Farah, M. E. (2003). Neovascular ingrowth site photothrombosis in choroidal neovascularization associated with retinal pigment epithelial detachment. Graefe's archive for clinical and experimental ophthalmology241(3), 245-250.
  13. Coscas, G., Koenig, F., & Soubrane, G. (1990). The pretear characteristics of pigment epithelial detachments: a study of 40 eyes. Archives of ophthalmology108(12), 1687-1693.
  14. Mudvari, S. S., Goff, M. J., Fu, A. D., McDONALD, H. R., Johnson, R. N., Ai, E., & Jumper, J. M. (2007). The natural history of pigment epithelial detachment associated with central serous chorioretinopathy. Retina27(9), 1168-1173.
  15. Loo, R. H., Scott, I. U., FLYNN Jr, H. W., Gass, J. D. M., Murray, T. G., Lewis, M. L., ... & Smiddy, W. E. (2002). Factors associated with reduced visual acuity during long-term follow-up of patients with idiopathic central serous chorioretinopathy. Retina22(1), 19-24.
  16. Blinder, K. J., Bradley, S., Bressler, N. M., Bressler, S. B., Donati, G., Hao, Y., ... & Pournaras, C. (2003). Effect of lesion size, visual acuity, and lesion composition on visual acuity change with and without verteporfin therapy for choroidal neovascularization secondary to age-related macular degeneration: TAP and VIP report No. 1. American journal of ophthalmology136(3), 407-418.