This case illustrates stability of an extrafoveal lesion without vision loss.
A woman aged 51 years attended for periodic eye examination with a complaint of blurry vision without correction only at near. Despite having diabetes for more than 5 years, managed with metformin (500 mg/d), she had corrected visual acuity of 20/20 in each eye at distance. She reported not knowing her A1C but admitted that her blood sugar values fluctuate above 100. In addition, she was treated medically for elevated cholesterol (rosuvastatin 20 mg/d), systemic hypertension (lisinopril 5 mg/d), and anxiety (medication unknown). Intraocular pressure was measured by Goldmann applanation tonometry at 14/12 mm Hg at 2:15 PM.The anterior segments were unremarkable and media were clear in each eye.See baseline fundus documentation of the left eye in Figure 1.
The media allow a good view of the fundus, the disc margins are distinct, the course and caliber of the retinal vasculature are appropriate, and the macula appears clear. Attention is drawn to the extramacular discolored area temporal to the macula, approximately 1 disc diameter in size that is elevated on stereoscopic examination. This finding would be consistent with pigment epithelial detachment (PED). Alternative diagnoses include choroidal neovascularization, a solid mass, or an inflammatory process.
On transillumination at slit-lamp biomicroscopy, there did not appear to be neovascular activity. Intraocularly, no inflammatory cells were observed. This left the most likely diagnosis of PED.
In the absence of a definitively effective treatment for PED, and because the patient had good visual acuity, as well as being asymptomatic, she was asked to return for follow-up in 1 year or, if symptoms arose, sooner. She returned 2 years later and her fundus is shown in Figure 2. The clinical information was unchanged at this visit except for some pigmentary attenuation, and the territory of the lesion did not appear to have changed. She was again asked to return in 1 year or sooner if visual symptoms arose.
She followed up 3 years later. The clinical details remained stable, and she enjoyed 20/20 visual acuity in each eye. Figure 3 documents pigmentary changes overlying the lesion but demonstrates stability of the area of involvement. At this visit, optical coherence tomography (OCT) was performed and is shown in Figure 4.
Note that the migration of retinal pigment corresponds with the color fundus photograph. This finding accounts for the apparent turbidity within the sub-retinal pigment epithelium (RPE) fluid. Turbidity of the subretinal fluid may suggest evolution to a neovascular event. Conversely, without the corresponding color fundus photograph, the inner retinal appearance may be confused with a drusenoid RPE detachment. She was again asked to return in 1 year or sooner if visual symptoms arose.
At the next follow-up visit, which was 4 years later, the patient developed lens opacity that obscures the retinal features, shown in Figure 5. The area of involvement remained stable, and, despite cataract formation, the patient maintained 20/20 visual acuity. OCT shows changes in the overlying retinal pigmentary changes but stability of the lesion. Significantly, the continued remodeling of the RPE appears to have consolidated within the original margins of the lesion. The importance was emphasized of maintaining closer adherence to follow-up as she ages, because of the possibility of encroachment on central vision or the potential for invasion of choroidal neovascularization.
Any discussion of PED should include classification and etiologies. PED can be associated with systemic or ocular conditions but may occur alone.1-3 Histologically, it presents as separation between the potential space between the RPE and underlying Bruch membrane. The space may be occupied by serous fluid, blood, drusenoid material, or a combination of all. The most frequently associated ocular condition is age-related macular degeneration (AMD) with myriad presentations. These may include encroachment of neovascular membranes from the choroid.2 When the presentation is central and involves a neovascular component, vision loss is a risk and treatment considerations become paramount.4
The pathophysiology of PED is not completely understood and most likely results from outer retinal layer dysfunction in conjunction with choroidal malfunction. This may be secondary to age-related deposition of lipids with secondary Bruch membrane thickening with alteration of choroidal permeability.5 PED may appear as solitary or multiple elevated fundus lesions that are seen at stereoscopic clinical evaluation. Basic diagnostic imaging methodologies include direct stereoscopic examination, as well as OCT.6 The appearance of orange rings is thought to be a sign of chronicity.7 This was not part of the clinical picture in the present case, which was followed for more than 7 years.
Any detailed discussion of PED should include ophthalmic, as well as systemic, conditions potentiating PED. At the head of the list on the ocular side are AMD and polypoidal choroidal vasculopathy.8 Inflammatory etiologies include complications secondary to systemic lupus erythematosus, inflammatory bowel disease, and sarcoidosis.8 Rare iatrogenic causes include reaction to intravenous infusion of bisphosphonates or pamidronate used in the treatment of osteoporosis.9 Renal insufficiency has been proposed as an underlying etiology of PED as it has been reported among patients who are not systemically hypertensive.10,11 Organ transplantation has been implicated as an etiology as well. Manifestation of PED during pregnancy suggests—along with its similarity to central serous chorioretinopathy—that the underlying mechanism may be related to elevated corticosteroid levels with the consequence of hyperpermeable choroid and dysfunctional RPE.12,13
Given that serous, drusenoid, and vascular presentation exist to specify PED, it is important to consider imaging that will offer definitive information on clinical characteristics. In the present case, OCT showed clear fluid in a later stage of the patient’s trajectory (Figure 6). Earlier, however, the PED could have been interpreted as being turbid (Figure 4). This apparent dilemma can be resolved by reconciling the clinical appearance manifesting pigment with the OCT. The OCT cross-section—horizontally and vertically—demonstrates shadowing that obscures the underlying outer retinal and choroidal structures. There is no evidence in Figure 4 of compromise of the retina-choroid interface. At the later evaluation, the pigment remains present but to a lesser extent and no confusion is present.
Serous PED is generally thought to have a more favorable natural course. Although serous PED may accompany the neovascular form of AMD, drusenoid presentations are more consistent with nonneovascular, or dry, AMD.2 Additional imaging studies may offer insight for distinguishing among PED subtypes. These modalities, in addition to clinical examination and color fundus photographic documentation, include fluorescein and indocyanine green angiography, fundus autofluorescence imaging, and conventional and enhanced depth imaging OCT.2 The increased availability of OCT angiography (OCT-A) may offer an additional avenue for diagnostic differentiation.
As with central serous chorioretinopathy, no definitively effective treatment for serous PED has been demonstrated. Strategies for vascularized PED include the spectrum of treatments for other neovascular entities such as laser photocoagulation, photodynamic therapy, intravitreal steroids, and anti-VEGF agents.5,14 Although larger lesions and those with a neovascular component centrally place patients at risk for vision loss, the present case illustrates stability of an extrafoveal lesion without vision loss. Consequences of resolved PED include complete resolution to RPE atrophy.15 For this reason, identification, subtyping, and location—especially of subtle PED—are important.
In summary, serous PED is a well-demarcated elevation of the RPE with subretinal fluid. A variety of imaging modalities may be employed to distinguish among the 3 main subtypes and form the basis for ongoing management. Despite PED’s relationship with AMD, no evidence of correlation to genetic risk alleles has been reported.