Optometry has widely adopted optical coherence tomography (OCT) as a mainstay in diagnosing and managing ocular disease since its advent in the 1990s
Optometry has widely adopted optical coherence tomography (OCT) as a mainstay in diagnosing and managing ocular disease since its advent in the 1990s. It provides a rapid, noninvasive, and detailed in vivo view of the retinal structure.
In keeping with OCT’s widespread popularity, it’s important to revisit basic findings and review easily avoided pitfalls one may encounter.
Related: The case of the disappearing drusen
Let’s take a look at six of them.
1. Back to basics: Where is the fluid?
Determining location is critical in the proper diagnosis and management in patients with fluid on OCT.
Fluid can be found in the intraretinal, subretinal, or subretinal pigment epithelium (RPE) space.
Intraretinal fluid is seen as rounded, hyporeflective spaces within the layers of the retina and is most commonly a manifestation of diabetes (Figure 1a), retinal vein occlusion, or intraocular inflammation.
Subretinal fluid appears on OCT as a space directly above the thick, hyper-reflective RPE complex. It is most commonly seen in cases of neurosensory retinal detachments (Figure 1b), central serous chorioretinopathy, and exudative age-related macular degeneration (ARMD) (Figure 1c). It is also a significant diagnostic factor in suspected choroidal melanomas1,2 because subretinal fluid represents a change in the metabolic function of the underlying RPE cells.
Sub-RPE fluid is seen as a space below the highly reflective RPE complex. In these instances, this finding is referred to as a pigment epithelial detachment (PED) (Figure 1d).
PEDs represent chorioretinal dysfunction, usually caused by inflammatory, ischemic, or degenerative processes.3
Central serous chorioretinopathy (CSCR) is a condition defined by choroidal congestion and hyperpermeability of choroidal vessels (Figure 1e). Frequently, CSCR is associated with PEDs and shallow macular neurosensory detachments, though both are not always present concurrently.
PEDs are also commonly seen in degenerative retinal conditions such as ARMD.4
In cases of multiple or hemorrhagic PEDs, polypoidal choroidal vasculopathy (PCV) (Figure 1f) must be on the top of a practitioner’s differentials.
Multifocal serous PEDs are also seen in hypertensive chorioretinopathy and multisystemic inflammatory conditions such as Vogt Kayanagi Harada disease, a T-cell mediated autoimmune disorder attacking melanocyte-related antigens.
2. Not all intraretinal spaces represent leakage
Intraretinal edema can result from a number of disease processes and is relatively common.
Some masqueraders of macular edema have a similar appearance but do not have the same primary leakage component and should be managed differently. Unlike true intraretinal edema, the masqueraders are not VEGF-mediated processes and therefore lack vascular permeability that leads to fluid accumulation.
Outer retinal tubulations (Figure 2a) appear as dark spaces encircled by a hyper-reflective band near the level of the RPE. They are seen in chronic degenerative retinal conditions (often ARMD) and are not responsive to treatment by anti-VEGF injections or anti-inflammatory medications such as steroids or NSAIDs. Rather, they are believed to represent a late or quiescent stage of disease5 due to disorganization of retinal anatomy and can be simply monitored.
OCT presentation of macular telangiectasia or “mac tel” can mimic choroidal macular edema (CME) as well. The most common subset (Type 2) has bilateral cavitary spaces near the fovea with a classic internal limiting membrane (ILM) drape directly above (Figure 2b).
Vision is typically better than 20/50, with half of eyes seeing better than 20/32.6
Treatment with intravitreal injections is reserved for neovascular cases, diagnosed with leakage on fluorescein and indocyanine green (ICG) angiography.7 As our understanding of this condition improves, newer technology like swept-source OCT-based microangiography (OCT-A) may prove to be a less-invasive and superior imaging technique for discovering neovascular membranes.8
Related: OCT in pediatric eye disease
Retinoschisis can also masquerade as CME. On OCT, schisis changes are seen as intraretinal ovoid spaces exhibiting “strand-like” separations.
Retinoschisis can be inherited, surgical, or acquired. The cyst-like retinal changes in cases of juvenile X-linked retinoschisis (JXLRS) (Figure 2c) or enhanced S cone syndrome (Goldmann-Favre) are resistant to treatment with intravitreal injections and show inconsistent results when treated with topical or oral carbonic anhydrase inhibitors such as dorzolamide or acetazolamide.9-11
Additional impersonators of CME make up the remainder of the non-leaking CME category. This group is defined by intraretinal cystoid spaces findings that do not show any leakage on fluorescein angiography.
The pneumonic typically used is the “JUNG and Restless use AT&T”, which stands for Juvenile X-linked retinoschisis, Usher syndrome, high-dose Niacin,12Goldmann-Favre, Retinitis pigmentosa,13 and the following chemotherapeutic medications Abraxane, Taxol, and Taxotere.
Non-leaking CME can also be seen in cases of myopic foveal schisis and pseudoholes with ERM.14 These cases of pseudo-macular edema are often resistant to traditional injections or topical medications, but the iatrogenic conditions respond positively to discontinuation of the causative agent.
3. Take a second look
Just as one cannot read a book without knowledge of individual words, accurate discernment of OCT images depends on a firm understanding of the individual retinal layers.
At first glance, an OCT image can lead us to believe retinal architecture is normal; though a closer inspection can reveal thinned, missing, or altered layers. On the contrary, the retina structure can appear nearly obliterated on OCT, but we are at times surprised to find that the vision is not as poor as we would anticipate.
Related: Affording OCT in your practice
When the macula appears normal on OCT, but a patient is suffering from unexplained vision loss, look closely at the superficial retina.
Ganglion cell and nerve fiber layer thinning can be due to a number of reasons. When this is the case, we must rule out optic neuropathies such as glaucoma or optic atrophy secondary to ischemic, infectious, or neoplastic etiologies. Studies have shown nerve fiber layer (NFL) thinning in cases of obstructive sleep apnea,15 systemic lupus erythematosus,16 and Alzheimer disease.17
Rarely, genetic disorders can cause acute and severe vision loss. In one case, a patient presented months after experiencing painless loss of vision that involved both eyes sequentially (Figure 3a). In this case, it would be easy to overlook the superficial layers.
Under more scrutiny, a nearly complete loss of the nerve fiber and ganglion cell layers temporally (white arrow) and significant thinning nasally (red arrow) is notable. Through genetic testing, the diagnosis of Leber’s hereditary optic neuropathy (LHON) was later confirmed.
Conversely, a patient’s vision may surprise us. Such is the case in this young female (Figure 3b) who was seeing 20/25 despite a suspected perimacular combined hamartoma of the retina and RPE causing tractional retinoschisis, epiretinal membrane formation, and a pseudohole.
Our asymptomatic patient’s excellent vision was the result of an intact photoreceptor integrity line (PIL) (red arrows), which is the connection between inner and outer portions of the photoreceptors.
Another patient (Figure 3c) saw 20/40 despite a large macular scar from presumed ocular histoplasmosis syndrome. The key in this patient is noting that the PIL (red arrow) is intact just up until the subfoveal area (white arrow); the scar is involving mostly the temporal fovea.
4. Vitreomacular something: VMA vs. VMT
Weakening of the vitreoretinal attachment is a natural result of an aging vitreous. Vitreoretinal adhesion is strongest at the vitreous base, peripapillary retina, macula, and blood vessels.
As the posterior vitreous begins to separate from the retina, the macular portion often remains attached more strongly. This can lead to vitreomacular adhesion (VMA) and vitreomacular traction (VMT).
VMA is described as a perifoveal vitreous separation with remaining vitreomacular attachment and undisturbed foveal morphology (Figure 4a).
VMT (Figure 4b) refers to a vitreomacular attachment with associated anatomic distortion of the fovea. Distortion can be seen in the form of macular thickening, pseudo-cysts, intraretinal schisis, elevation of the retinal floor, and flattened foveal contour.
The area of adhesion for both conditions is defined as broad or focal, being more or less than 1500 µm of attachment, respectively, and can be measured using the caliber tool with most OCT software.18
It is important to note that VMA is asymptomatic, but VMT can produce symptoms such as blur, micropsia, and central distortion. Therefore, patients presenting with visual symptoms who are found to have VMA must be evaluated closer for other etiologies of their distortion.
VMT can present with cystoid changes in the retina that resemble edema, create a pseudohole, or eventually lead to a macular hole. For symptomatic focal VMT in a specific subset of patients, an intravitreal injection of a plasminogen may hasten resolution of traction by breaking down vitreal adhesive molecules or simply by sheer mechanical force.
Exudative ARMD in individuals with VMT is often less responsive to anti-VEGF therapies and is associated with worse outcomes.19
5. What lies beneath: Don’t forget the choroid
When we come across a patient with a maculopathy, we often focus our attention solely on the retina and forget a key element. Because the choroid is the crucial blood supply for the outer retina, ignoring it is a mistake, and it can make all the difference in accurately diagnosing a challenging case.
For this purpose, enhanced depth imaging OCT (EDI OCT) and swept-source OCT (SS-OCT) can provide the best images, but visualization of choroidal structure on standard OCT is improving with newer technologies.
It is well-known that choroidal thickness is negatively correlated with increasing age, though individuals with ARMD (Figure 5a) have even thinner choroids than their age-matched peers.20
High myopia is also strongly associated with choroidal thinning (Figure 5b) at a rate of approximately 8.7 µm per diopter of myopia according to one study.21
Pathologic thinning of the choroid increases the risk of choroidal neovascular membrane (CNVM) formation, which often leads to retinal atrophy, chorioretinal scarring, and ultimately loss of vision.
Choroidal thinning isn’t the only thing that poses a problem with the health of the retina. Abnormal thickening can also be a sign of choroidal dysfunction and congestion, leading to manifestations such as PEDs, CNVMs, and neurosensory detachments. Current understanding identifies three main diseases in this “pachychoroid” spectrum: Central serious chorioretinopathy (CSCR), polypoidal choroidal vasculopathy (PCV), and pachychoroid pigment epitheliopathy (PPE).
CSCR is a condition historically associated with high levels of stress, middle-aged males, and use of corticosteroids. It is an easy, slam-dunk diagnosis in conventional cases but remains difficult to definitively diagnose in many patients due to its range of presentations.
CSCR is caused by choroidal congestion and hyperpermeability of vessels, leading to PEDs and shallow neurosensory detachments of the macula. It can be asymptomatic or create visual disturbances such as metamorphopsia or visual acuity loss.
OCT often exhibits choroidal thickening under the macula, and it has been noted that those with a chronic form of the condition had thicker choroids than those with acute forms.22 When CSCR is chronic, one may see other funduscopic signs, such as macular pigmentary changes, inferior retinal detachments (due to gravity pulling fluid), and “guttering” (RPE changes tracking from the macula downward, Figure 5c).
PCV also has a thicker-than-average choroid23 and is defined by aneurysmal dilations of the choroidal vessels leading to multiple serosanguineous RPE detachments (Figure 5d) and exudative changes. The dilations may be seen on funduscopy but are best viewed with ICG angiography.
Typically, the distinction between CSCR and PCV can easily be made, but the picture can become clouded when CSCR becomes chronic.24 Differentiation is important because the natural history and treatment differs greatly.
PPE25,26 is the newest member of the pachychoroid family, and it is thought to be an early “form fruste” CSCR. It is defined by an increased choroidal thickness, minimal or absent choroidal vascular dilations funduscopic evaluation, and drusenoid RPE changes or small PEDs overlying dilated choroidal vessels.
Patients with PPE do not have a history of serous macular detachments and are therefore considered to have a premature form of CSCR.
6. All drusen are created equally, right?
Not all drusen are the same, and they can be easily differentiated by combining funduscopy with OCT. Though they all may lead to vision loss, recognizing the specific subset can often give insight into prognosis.
Related: Diagnosing retinal artery occlusions
The “typical” drusen we are most likely familiar with are located between the RPE and Bruch’s membrane. They are a marker for ARMD, and we can classify them based on funduscopic appearance.
Basal laminar drusen (BLD) were originally referred to as the misnomer “cuticular drusen” prior to the advent of electron microscopy.27 They consist of thickened nodular portions in the basement membrane of RPE cells.
On OCT, they exhibit a thickened “sawtooth” RPE pattern (Figure 6a, red bracket). On funduscopy, they are typically seen as small clusters of yellow deposits (Figure 6b).
The BLD are seen at earlier ages than typical age-related drusen and are more common in females. These patients have a higher incidence of vitelliform macular detachments (Figure 6a, white arrow) that may be associated with neovascular membranes.
Reticular drusen, or pseudodrusen, are bilateral and seen funduscopically as an interconnected network pattern that appears most prominently near the superotemporal arcade. They are best visualized with auto-fluorescence (Figure 6c). On OCT, the drusen are subretinal, lying above the RPE.
They are associated with later onset of vision loss (compared to ARMD with typical drusen) and are more commonly seen in females.28 They may have a higher incidence of affiliation with conversion to neovascular ARMD via retinal angiomatous proliferation29 and are frequently combined with typical macular ARMD drusen.
Autosomal dominant radial drusen (ADRD) also goes by the aliases of familial dominant drusen, Malattia Leventinese, and Doyne honeycomb choroiditis, though the last two terms are outdated. The drusen seen in this specific form of retinal degeneration are yellow-white and deposited in a radial pattern. The elongated drusen are found temporally and may also be seen nasal to the disc, which is unlikely in other forms of macular degeneration.
They appear by the second or third decade and result in earlier onset of vision loss, often by the fifth decade.30 On OCT, they are sub-RPE and can form drusenoid PEDs (Figure 6d).
Optical coherence tomography allows us to evaluate the retina on a real-time, microscopic level. As OCT technology continues to make strides, our knowledge of the retina and its physiologic response to diseases will improve. The better our understanding of anatomical changes of the retina and choroid on OCT, the better prepared we can be to make important clinical distinctions and decisions in the care of our patients.
Related: Misdiagnosing macular degeneration
1. Shields CL, Furuta M, Berman EL, Zahler JD, Hoberman DM, Dinh DH, Mashayekhi A, Shields JA. Choroidal nevus transformation into melanoma: analysis of 2514 consecutive cases. Arch Ophthalmol. 2009 Aug;127(8):981-7.
2. Materin MA, Raducu R, Bianciotto C, Shields CL. Fundus autofluorescence and optical coherence tomography findings in choroidal melanocytic lesions. Middle East Afr J Ophthalmol. 2010 Jul;17(3):201-6.
3. Nicholson B, Noble J, Forooghian F, Meyerle C. Central serous chorioretinopathy: update on pathophysiology and treatment. Surv Ophthalmol. 2013 Mar-Apr;58(2):103-26.
4. Zayit-Soudry S, Moroz I, Loewenstein A. Retinal pigment epithelial detachment. Surv Ophthalmol. 2007 May-Jun;52(3):227-43.
5. Schaal KB, Freund KB, Litts KM, Zhang Y, Messinger JD, Curcio CA. Outer retinal tubulation in advanced age-related macular degeneration: Optical coherence tomographic findings correspond to histology. Retina. 2015 Jul;35(7):1339-50.
6. Clemons TE, Gillies MC, Chew EY, Bird AC, Peto T, Figueroa MJ, Harrington MW; MacTel Research Group. Baseline characteristics of participants in the natural history study of macular telangiectasia (MacTel) MacTel Project Report No. 2. Ophthalmic Epidemiol. 2010 Jan-Feb;17(1):66-73.
7. Kupitz EH, Heeren TF, Holz FG, Charbel Issa P. Poor long-term outcome of anti-vascular endothelial growth factor therapy in nonproliferative macular telangiectasia type 2. Retina. 2015 Dec;35(12):2619-26.
8. Zhang Q, Wang RK, Chen CL, Legarreta AD, Durbin MK, An L, Sharma U, Stetson PF, Legarreta JE, Roisman L, Gregori G, Rosenfeld PJ. Swept source optical coherence tomography angiography of neovasuclar macular telangiectasia type 2. Retina. 2015 Nov;35(11):2285-99.
9. Genead MA, Fishman GA, Walia S. Efficacy of sustained topical dorzolamide therapy for cystic macular lesions in patients with X-linked retinoschisis. Arch Ophthalmol. 2010 Feb;128(2):190-7.
10. Gurbaxani A, Wei M, Succar T, McCluskey PJ, Jamieson RV, Grigg JR. Acetazolamide in retinoschisis: a prospective study. Ophthalmology. 2014 Mar;121(3):802-3.e3.
11. BuÅ¡iÃ‡ M, BjeloÅ¡ M, Bosnar D, RamiÃ‡ S, BuÅ¡iÃ‡ I. Cystoid macular lesions are resistant to topical dorzolamide treatment in enhanced S-cone syndrome child. Doc Ophthalmol. 2016 Feb;132(1):67-73.
12. Bressler NM. Cystoid macular edema from niacin typically is not accompanied by fluorescein leakage on angiography. Am J Ophthalmol. 2005 May;139(5):951; author reply 951.
13. Lai YH, Capasso JE, Kaiser R, Levin AV. Intraretinal cystoid spaces in a patient with retinitis pigmentosa due to mutation in the MAK gene. Ophthalmic Genet. 2016 Feb 19:1-3.
14. Gerstenblith, A.T. and M.P. Rabinowitz, The Wills Eye Manual: Office and Emergency Room Diagnosis and Treatment of Eye Disease. 2012: Wolters Kluwer/Lippincott Williams & Wilkins.
15. Ferrandez, B., et al., Assessment of the retinal nerve fiber layer in individuals with obstructive sleep apnea. BMC Ophthalmol, 2016. 16: p. 40.
16. Liu GY, Utset TO, Bernard JT. Retinal nerve fiber layer and macular thinning in systemic lupus erythematosus: an optical coherence tomography study comparing SLE and neuropsychiatric SLE. Lupus. 2015 Oct;24(11):1169-76.
17. Kirbas S, Turkyilmaz K, Anlar O, Tufekci A, Durmus M. Retinal nerve fiber layer thickness in patients with Alzheimer disease. J Neuroophthalmol. 2013 Mar;33(1):58-61.
18. Duker JS, Kaiser PK, Binder S, de Smet MD, Gaudric A, Reichel E, Sadda SR, Sebag J, Spaide RF, Stalmans P. The International Vitreomacular Traction Study Group classification of vitreomacular adhesion, traction, and macular hole. Ophthalmology. 2013 Dec;120(12):2611-9.
19. Krishnan R, Arora R, De Salvo G, Stinghe A, Severn PS, Pal B, Goverdhan S. Vitreomacular traction affects anti-vascular endothelial growth factor treatment outcomes for exudative age-related macular degeneration. Retina. 2015 Sep;35(9):1750-6.
20. Manjunath V1, Goren J, Fujimoto JG, Duker JS. Analysis of choroidal thickness in age-related macular degeneration using spectral-domain optical coherence tomography. Am J Ophthalmol. 2011 Oct;152(4):663-8.