This article explores the use of OCT for the detection, diagnosis and management of macular abnormalities. The author uses a series of case studies to illustrate examples of pathology that may present in routine practice.
Since optical coherence tomography (OCT) was first demonstrated in 1991,1 it has rapidly evolved as the only non-invasive diagnostic technique able to provide images of the retinal microstructure, directly relating to the histological structure of the retina (see Figure 1: Swept source OCT B-scan with nomenclature of normal anatomic landscapes as proposed and adopted by the International Nomenclature for Optical Coherence Tomography).2 With use of OCT growing dramatically over the last few years, this article reviews four patient cases presenting within primary eye care. Identification of pathology with OCT will be discussed, along with appropriate referral criteria and treatment options available.
Case 1An 81-year-old female patient presented for a routine eye examination with no ocular complaints. There were no general health concerns and no family general or ocular health history. Refraction showed no change and visual acuity (VA) in both eyes was stable at 6/7.5 Binocular indirect examination of the right fundus showed extensive exudates between the macula and disc (see Figure 2A: Case 1 showing a large fibrovascular PED: photo). Examination of the central fovea was unremarkable. OCT examination revealed the presence of a large pigment epithelial detachment (PED) (see Figure 2B: A high resolution OCT B-scan enabling enhanced visualisation of the sub-RPE space. The B-scan shows exudates nasally, appearing as hyper-reflective spots within the outer plexiform layer with shadowing behind the exudates).
While vision remained stable in this patient – likely due to the absence of sub-retinal and intraretinal fluid and the maintained integrity of the photoreceptor complex – as wet AMD was suspected the patient was referred via a fast track macular service. Fluorescein angiography examination, which was performed within 10 days of the original referral, confirmed OCT findings of a right occult CNVM. However, with VA of 6/7.5, the patient fell outside NICE guidance for treatment with the anti-VEGF therapy, Lucentis (ranibuzumab), which states that VA must be between 6/12 and 6/96.6 The patient was advised to self-monitor with an Amsler grid and would be reassessed on a monthly basis with OCT.
As this patient has wet AMD in her right eye and dry AMD In the left eye, it would be advisable to offer nutritional supplementation. In a patient with these characteristics, supplementation with the AREDS 2 formula (10mg lutein, 25mg zinc, 2mg copper, 500mg vitamin C and 400IU vitamin E) could reduce risk of progression to advanced AMD by 18–25%, depending on dietary intake of nutrients.7 Nutritional supplementation with antioxidants is believed to reduce the risk of AMD progression by reducing the level of oxidative stress at the retina, one of the most popular hypotheses regarding AMD development and progression.8,9
￼A 72-year-old female patient attended for a contact lens aftercare complaining of a two-week history of reduced VA in the left eye at all distances with associated metamorphopsia. Refraction was unchanged with a VA of 6/19-2 that showed no improvement with pinhole. VA was measured at 6/6-2 six months previously. Dilated binocular indirect examination of the macula showed no obvious abnormality. OCT examination showed a Stage 2, full thickness macular hole with persistent vitreous attachment (see Figure 3: Case two showing fundus photograph (top) and OCT B-scan (below) with a Stage 2, full-thickness macular hole and persistent vitreous attachement). Macular hole development in this case is secondary to vitreomacular traction, which can occur during the process of posterior vitreous detachment (PVD).Incidence of PVD is known to increase with age; reports of PVD in emmetropic subjects are rare under 40 years of age, with the incidence rising with age to 50% at 50 years, 65% beyond 65 years and up to 87% beyond 90 years.10,11 Risk factors associated with earlier onset of PVD include myopia, ocular trauma, ocular surgery, aphakia, intraocular inflammation, diabetes and postmenopausal women.12-14
While the majority of PVDs occur without complications, attachment may persist at the central macula and cause traction; this is known as vitreomacular traction (VMT). The incidence of VMT appears to be slightly higher in women, which is attributed to premature vitreous liquefaction and earlier onset PVD. The clinical picture in VMT is highly variable, with symptoms ranging from mild blurring and distortion to severe decrease in VA (< 6/18) with severe distortion.15 However, symptoms are usually mild with slow reduction of vision due to chronic traction. If the patient is relatively asymptomatic and VMT is a chance finding, patients should be advised to self-monitor with an Amsler grid and reviewed to see if spontaneous resolution or progression occurs.16If VMT persists during PVD it can lead to the formation of a macular hole, as in the case presented here. Macular holes are typically seen in females in the sixth or seventh decade of life, with a prevalence of 1/3300.17 It is now accepted that the early event leading to macular hole formation is persistent vitreoretinal traction. Macular holes can be classified using OCT into four stages as follows:
- Stage 1 Vitreomacular traction, with flattening of the foveal dip and a small reduction in VA
- Stage 2 Small full-thickness macular hole of less than 250μm diameter with persistent vitreomacular adhesion
- Stage 3 Medium-sized full-thickness macular hole between 250–400μm in diameter with persistent vitreomacular adhesion
- Stage 4 Large full-thickness macular hole over 400μm in diameter without vitreomacular adhesion
According to the above grading, the patient described in the case study is classified as having a Stage 2 macular hole. Previously, the only treatment option available for this patient would have been vitrectomy. However, advances in pharmaceuticals have led to the development of ocriplasmin (Jetrea), an intravitreal injection containing protease enzyme, which breaks down the vitreoretinal attachments, inducing PVD.18 Although NICE approved since 2013, strict criteria restrict the use of ocriplasmin to patients who have no epiretinal membrane (ERM), a Stage 2 full-thickness macular hole (diameter less than 400μm) and/or severe visual symptoms.19 In addition, due to the high cost of the drug (£2500 per injection), use varies across the country, depending on approval in different health boards. Ocriplasmin has been found to induce PVD in up to 37.4% of patients with VMT alone, and up to 50% of patients with VMT and macular hole.16
A female patient originally presented in 2008 at the age of 30, with a one year history of central serous chorioretinopathy (CSR) in the right eye which was diagnosed within the hospital eye service.￼
The first OCT examination was performed on this patient in 2010 when VA was 6/15 accompanied by a small hyperopic refractive shift and symptoms of distortion and reduced vision. In 2010, OCT examination showed an extensive, oval shaped area of sub-retinal fluid extending from the macula to the disc with accompanying RPE disruption (see Figure 4A: Case 3 showing central serous chorioretinopathy (CSR) in 2010 with OCT). In 2012, the patient returned for a routine examination following previous laser treatment within the hospital eye service. Vision was reported as stable and VA was 6/15-. OCT examination shows no sub-retinal fluid centrally, but persistent fluid nasal to the macula and extending to the disc (see Figure 4B: Case 3 showing CSR in 2012 with OCT). Careful OCT assessment shows significant retinal thinning, particularly within the outer nuclear layer and with the external limiting membrane and ellipsoid zone (IS/OS junction) no longer clearly visible. Examination in 2013 when the patient reported no noticeable change in vision showed recurrence of sub-retinal fluid centrally and reduced VA to 6/48 (see Figure 4C: Case showing CSR in 2013 with OCT). Re-referral to the hospital eye service was made at this stage, with the patient reviewed within one month of referral. Fluid then reabsorbed in 2014 and VA had improved to 6/18 (see Figure 4D: Case showing CSR in 2014 with OCT). While the patient was under the care of the hospital in 2011, choroidal folds were noted (see Figure 5: Fundus photography from 2011 shows presence of choroidal folds). CT scans were performed to rule out the presence of an orbital space-occupying lesion.
Central serous retinopathy (CSR) is a sporadic disorder of the outer blood-retinal barrier, typically affecting young to middle-aged men with Type A personality.20 CSR is reportedly aggravated by stress, untreated hypertension, high alcohol intake and corticosteroid use.21 The pathophysiology of CSR is still poorly understood; however, research using indocyanine green angiography (ICG) has shown multiple areas of choroidal vascular hyperpermeability, vascular congestion and venous dilation,22 suggesting that CSR is associated with a generalised choroidal vascular disturbance.23
Symptoms of CSR often include metamorphopsia, blurred vision and relative positive scotoma. OCT examination of CSR is characterised by a well-defined round or oval serous detachment of the sensory retina in the macular area, as seen in this patient case. An accompanying RPE defect can often be seen, with serous PEDs noted in up to 63% of cases.24
Spontaneous resolution and absorption of fluid occurs in most cases of CSR within three to six months, with return to normal or near-normal vision. However, recurrence does occur in up to 50% of cases.25 Recurrent CSR is associated with a poorer visual prognosis, with reduced VA, decreased stereopsis and impaired colour vision.26 Chronic CSR, in which fluid persists for more than six months, represents only approximately 5% of CSR cases and is characterised by RPE atrophy, RPE pigmentary abnormalities and pigment clumping.25,26 Thinning of the neurosensory retina – as noted in this patient case – is another sequela than can occur in chronic CSR and results in a reduction of central retinal thickness by up to 50%.26
While treatment is not indicated in a high proportion of CSR cases due to spontaneous resolution, treatment of prolonged or chronic CSR is typically with laser or photodynamic therapy (PDT).27 Treatment is often considered after two to four months of persistent sub- retinal fluid in order to avoid irreversible photoreceptor atrophy.28 In argon laser treatment, the leakage site – as identified with fundus fluorescein angiography – is targeted. The proposed mechanism of action of this treatment is photocoagulation of RPE cells at the site of leakage, which forms a fibrotic scar thus preventing further focal leakage. Treatment of this type can accelerate recovery by approximately two months.29
This final case study follows a 74-year-old female patient who presented complaining of reduced vision in the left eye, with VA measuring 6/18+2. OCT examination showed a significant epiretinal membrane (ERM) with associated retinal thickening (see Figure 6: Case 4 with OCT B-scans showing the pre-operative presence of ERM with pucker and retinal thickening (A) and post-operative results showing absence of ERM but persistent pucker and retinal thickening (C). The pre- (B) and post-operative (D) ETDRS girds show a general reduction in retinal thickness across all retinal areas). Due to reduced VA and associated symptoms of distortion, the patient was referred to the hospital eye service for review with a vitreoretinal surgeon.
Vitrectomy with membrane peel was performed within five months of referral. While VA recovered to 6/7.5 following surgery, metamorphopsia remained, likely due to the persistent ‘pucker’ which can be seen on OCT.
PVD is believed to have a critical role in the pathogenesis of idiopathic ERM. The prevalence of ERM in large scale studies has been reported to be between 2.2– 26.1%.30 Large scale clinical studies have shown that 80–95% of eyes with idiopathic ERM have either a partial or complete PVD.31 Other causes for the development of ERM comprise: retinal surgery including photocoagulation and cryotherapy; retinal vascular disease; intraocular inflammation and ocular trauma. With no history of surgery, trauma or retinal vascular disease, PVD is the likely cause of ERM development in this patient.
The process by which PVD stimulates ERM formation is believed to be caused by one of two mechanisms.32 First, tractional forces during PVD results in breaks in the retina’s inner limiting membrane, allowing migration of glial cells (non-neuronal retinal cells that provide neuronal support) to the inner retinal surface where they proliferate. Alternatively, ERMs may result from the transdifferentiation (cell conversion) and proliferation of hyalocytes of vitreous origin that are left behind on the retinal surface following PVD.33
The clinical appearance of ERM can vary dramatically depending on their thickness and associated distortion of retinal vasculature. When the membrane is thin and translucent, it is often referred to as ‘cellophane maculopathy’. In these cases the membrane is seen on fundoscopy as an irregular light reflex or sheen over the macula. As the membrane thickens and contracts it creates retinal folds and is known as ‘macular pucker’. Unlike cellophane maculopathy where vision can remain relatively unaffected, macular pucker typically causes reduction in vision to 6/12 or worse, with associated metamorphopsia.30 In severe cases, ERM is associated with retinal thickening and oedema; this is believed to be caused by mechanical stress resulting in retinal Müller cells releasing inflammatory factors causing localised inflammation and breakdown of the blood retinal barrier.34
The only treatment available for ERM is vitrectomy and membrane peel, as performed with this patient. Visual outcome following surgery varies depending on pre-operative visual acuity, with higher visual outcome achieved in patients with better initial VA.35 Typically, visual improvement is achieved in between 70–90% of patients, with a mean improvement in vision by more than two lines of Snellen acuity. Visual acuity can take up to one year to settle down following surgery.36 Recurrence of ERM following surgery is high, occurring in up to 16.5% of cases.37
The cases illustrated here demonstrate the value of OCT in the detection, diagnosis and monitoring of a variety of macular pathologies. Timely recognition of these abnormalities is important in helping to provide the best visual outcome for the patient.
About the author
Dr Rachel Hiscox is the education and clinical affairs manager for Topcon GB and an optometrist with experience in both hospital and high street optometry. Rachel gained a PhD from Cardiff University in 2013 investigating the retina in Cystic Fibrosis.
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