Dr Lindsay Howse OD
Dr Julie Rodman
OD MS FAAO
Nova Southeastern University, College of Optometry, Fort Lauderdale FL, USA
Retinitis pigmentosa (RP) is defined as a group of rare, hereditary retinal diseases that result in progressive loss of photoreceptors. Patients typically present with nyctalopia and progressive loss of peripheral vision.1
For many years, the focus of RP has been on understanding the pathophysiology of the disease and identifying the various structural abnormalities that manifest throughout the disease progression, including arteriole attenuation, waxy optic nerve pallor, bone spicule formation, posterior subcapsular cataracts and macular mottling.
Optical coherence tomography angiography (OCT-A) is a new, innovative, non-invasive imaging modality that allows for advanced imaging and analysis of the macular vascular changes associated with RP that have not been previously reported. These findings have provided additional insight into the pathophysiology behind the disease, suggesting involvement at the level of the inner retina. We present three cases of RP at varying stages to highlight the changes in macular vascular density throughout the retinal and choroidal layers as the disease progresses.
CASE REPORT 1
An 18-year-old African American male presented with a history of unknown retinal dystrophy, presumed RP.
Two years previously, a prior doctor had suspected RP based on mild clinical signs but was unable to confirm without electroretinography. The patient had no complaints of decreased night vision or peripheral vision. After probing, the patient reported a slight delay in visual recovery after looking at bright lights. The patient denied a family history of RP. His systemic history was unremarkable and he was not taking any medications.
Best corrected visual acuities were 6/6 OD, OS. Pupils, confrontations, extraocular motility and colour vision were found to be normal. Intraocular pressure measured 11 mmHg OD, OS. Anterior segment findings were unremarkable, with no posterior subcapsular cataracts. Both eyes exhibited similar findings on fundus evaluation. The optic nerves were pink and healthy, C/D ratio was 0.3, with no waxy pallor. The macula was intact, with no haemorrhaging, oedema or mottling. Retinal vasculature demonstrated slight vessel attenuation. In addition, there was mild bone spicule formation in the periphery and mid-periphery.
SD-OCT of the macula appeared healthy with no apparent structural abnormalities. Vascularisation of the retinal layers was visualised and segmented using OCT-A. In addition, objective quantification of vessel density was evaluated for each eye using the AngioVue software.
Analysis of the angiograms revealed decreased retinal vascular perfusion and capillary density in both the superficial capillary plexus (SCP) and deep capillary plexus (DCP) with no apparent abnormality at the choriocapillaris. Careful evaluation of the vessel density maps revealed more significant loss at the level of the SCP than the DCP (Figure 1).
Figure 1. OCT angiography and SD-OCT of the right and left eye of a patient with mild retinitis pigmentosa
Despite the relatively quiescent nature of the fundus appearance and SD-OCT, OCT-A was able to detect and localise irregularities in vascular flow within the inner retina in this patient with mild disease.
CASE REPORT 2
A 27-year-old Hispanic male presented with the chief complaint of diminution of vision in both eyes and a history of RP.
His systemic history was unremarkable and he was taking no medications. Best corrected visual acuities were 6/7.5- OD, OS. Pupils, confrontations, extraocular motility and colour vision were found to be normal. Intraocular pressure was measured to be 14 mmHg OD and 15 mmHg OS. Anterior segment findings were unremarkable, with no posterior subcapsular cataracts. Posterior segment findings of both eyes revealed mild pallor of the optic nerves with 0.3 round C/D ratio. The macula was intact, with no haemorrhaging, oedema or mottling. A mild epiretinal membrane was present in the macula right eye, greater than left eye. The retinal vessels exhibited mild vessel attenuation. The periphery was flat and intact with bone spicule retinal pigment epithelial clumping in all quadrants.
Significant findings on the SD-OCT included epiretinal membrane and slight disruption of the photoreceptor integrity line in both eyes. OCT-A revealed an enlarged foveal avascular zone with abnormally low vascular density in the superficial and deep capillary plexus with more significant involvement of the deep capillary plexus with no apparent abnormality seen at the level of the choroid (Figure 2). With moderate RP, as seen with this patient, the DCP appears to be more significantly involved than the SCP, although both complexes are severely compromised.2
Figure 2. OCT angiography and SD-OCT of the right and left eye of a patient with moderate retinitis pigmentosa
CASE REPORT 3
A 56-year-old Hispanic male presented with a chief complaint of blurry vision and decreased peripheral vision in both eyes.
The patient had been diagnosed with RP 20 years prior in Cuba. His systemic history was unremarkable and he was taking no medications. The patient reported a family history of RP and diabetes mellitus type 2.
Best corrected visual acuities were 6/18 OD and 6/15 OS. Extraocular motility was full; however, confrontation fields were significantly reduced in all quadrants in both eyes. Pupils were normal with no APD. The patient failed the HRR colour vision screening in both eyes. Intraocular pressure was measured to be 14 mmHg OD, OS. Anterior segment findings revealed mild meibomian gland disease, pinguecula, trace amount of pigment on the corneal endothelium, and PC IOL with 1+ diffuse PCO in both eyes. Significant posterior segment findings of both eyes included: waxy pallor of both optic nerves with 0.2 C/D ratio, retinal vascular attenuation, pigmentary changes and RPE mottling of the macula, and bone spicule RPE clumping in the periphery in all quadrants.
SD-OCT showed mild macular oedema with cystic pockets of fluid in both eyes, but visual acuity was only mildly affected due to preservation of the photoreceptor integrity line and ellipsoid zone at the fovea. OCT-A showed decreased vascular density in the SCP and DCP with the left eye affected more than the right eye. Mild changes were observed at the level of the choriocapillaris, but most of the change was observed in the SCP and DCP with the DCP more severely impacted than the SCP (Figure 3). The OCT-A density maps confirmed that the severity of disease correlated with reduction in vascular density within the inner retinal SCP and DCP, with reduction in DCP directly related to visual function.
Figure 3. OCT angiography and SD-OCT of the right and left eye of a patient with advanced retinitis pigmentosa
Retinitis pigmentosa is the term used to designate a group of inherited retinal disorders characterised by progressive loss of photoreceptors and retinal dysfunction resulting in deterioration of central vision.1 RP is characterised by classic symptomatology and clinical findings including nyctalopia, visual field constriction, bone spicule pigmentation and abnormal full-field electroretinograms. RP affects the photoreceptor-RPE cell metabolic complex and begins with a loss of the rod photoreceptors as evidenced by the initial involvement of the equatorial and peripheral retina.
Over time, the cone photoreceptors become involved, resulting in progressive visual loss. Histopathological studies have identified shortening of the photoreceptor outer segments as the earliest identifiable finding in RP.2 Typical clinical features of RP include peripheral retinal bone-spicule deposition, optic nerve pallor and retinal vessel attenuation. Loss of normal retinal vasculature is believed to be due to photoreceptor degeneration.3
Abnormalities within the retinal vasculature as well as changes in ocular blood flow have been implicated in the pathogenesis of RP. In fact, fluorescein angiography and indocyanine green angiography have illustrated the abnormal retinal and choroidal vasculature in RP noting increased dye transit time, narrowed vessel lumen and reduced dye concentration.4 In addition, electoretinogram shows increased arteriovenous transit time and reduced blood flow velocity.5
Since the advent of OCT, it has become the standard for assessing anatomical abnormalities via high resolution tomographic images. OCT is able to accurately assess the photoreceptor segments and thicknesses of retinal layers in RP patients and has shown a decrease in foveal thickness, interruption of the IS/OS junction, and reduction in choroidal thickness.5 Correlations between the retinal structure and visual acuity have been identified in affected patients.
Historically, RP has been characterised as a disease of the photoreceptors with loss of the outer retinal cells. However, new research is identifying disorganisation and damage to the inner retina including death of the retinal ganglion cells. Outer retinal involvement can occur as a result of chronic apoptosis of the ganglion cells and disorganisation of the inner retina.6-8
OCT-A is a recently developed, non-invasive, contrast-free technique for imaging the retinal and choroidal microvasculature. The technique uses the movement of red blood cells in the retinal vasculature to create an image of retinal blood flow. This allows for segmentation and evaluation of all retinal layers and capillary networks. Analysis of OCT-A images in RP patients has confirmed the aforementioned involvement of the inner retinal layers in the pathogenesis of RP.
It has been documented that photoreceptor damage leads to changes in the inner retinal tissue including the retinal ganglion cells. Despite varying hypotheses regarding the morphological changes to the inner retina, a direct correlation has been found between ganglion cell thickness and macular function in RP patients. Furthermore, it appears that the multi-focal electroretinogram is negatively affected by apoptosis of the ganglion cells.9
The resolution provided by OCT-A has provided outstanding visualisation of the SCP and DCP vascular networks within the inner retina and has been able to identify varying features that cannot be distinguished by classical fluorescein angiography. The superficial vascular plexus is located in the ganglion cell layer and in the nerve fibre layer. The deep vascular plexi are located in the inner nuclear layers and external plexiform layer.
OCT-A illustrates different morphological features of the retinal blood supply for the two plexi.10 The vascular supply of the superficial plexus is characterised by multiple linear structures having a centripetal distribution converging towards the fovea. Secondary vessels arise from the main vessels forming a web-like pattern. The calibre of the vessels is uniform throughout the scan. The deep plexus comprises an interwoven pattern of vessels that surround the foveal avascular zone in numerous horizontal and radial interconnections. The calibre of the vessels is also uniform throughout the scan.11,12
OCT-A in patients with RP demonstrates alterations in the normal vasculature within the superficial and deep retinal layers as well as throughout the choroid. The SCP and DCP vessel densities are reduced in patients with RP.9 It has been postulated that this reduction in blood flow occurs early in the disease process and leads to eventual ischaemia, retinal vessel damage and cell death involving both the inner and outer retinal space. Furthermore, vessel density abnormalities at the level of the DCP appear to be directly related to macular function and visual potential.
Analysis of the three patients presented in this article suggests that severity of disease correlates with degree of reduction in vascular flow as seen on the segmented angiograms as well as with diminution in the vessel density map (Figure 4).
Figure 4. OCT angiography showing the macular capillary density of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris of various stages of retinitis pigmentosa (RP) compared to those of a normal patient
Because OCT-A is able to identify and quantify loss of normal retinal vasculature in RP patients, it should be used to monitor disease progression in affected patients. Vascular changes may precede functional changes as seen on visual field testing and may thus play a pivotal role in staging and categorising the disease.
OCT-A provides excellent insight into the microvascular changes occurring throughout the retina and choroid and allows for additional insight into the pathophysiology behind the disease. It appears that alterations in the vascular density and pattern of flow seen on angiogram correlate with disease severity. OCT-A may exhibit signs of disease earlier and should be utilised to provide timely management of affected patients.
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- Zhang Q, Lee CS, Chao J, Chen CL, et al. Wide-field optical coherence tomography based microangiography for retinal imaging. Nature 2016; 6: 22017.
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- Toto L, Borrelli E, Mastropasqua R, Senatore A, et al. Macular features in retinitis pigmentosa: correlations among ganglion cell complex thickness, capillary density, and macular function. Invest Ophthalmol Vis Sci 2016; 57: 6360-6366.
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- Lumbroso B, Huang D, Jia Y, et al. Clinical Guide to Angio-OCT Non Invasive, Dye-less OCT Angiography. 1st ed. New Delhi, India: Jaypee Brothers Medical Publisher: 2015.
- Savastano MC, Lumbroso B, Rispoli M, In Vivo Characterization of retinal vascularization morphology using optical coherence tomography angiography. Retina 2016; 35: 2196-2203.