Optical Coherence Tomography Angiography for Choroidal and Vitreoretinal Disorders – Part 2

Venous drainage from the retina merges into the central retinal vein and can be obstructed in the branch veins that drain the retinal quadrants, or the central retinal vein itself, which are termed Branch Retinal Vein Occlusion (BRVO) and Central Retinal Vein Occlusion (CRVO), respectively. Obstruction of retinal venous drainage often leads to a sudden or progressive increase in distal venous and capillary pressure with loss of vision and visual field defects. The extent of visual impairment correlates with the location and severity of the venous occlusion and how it impacts perfusion in the retina. Macular edema or retinal ischemia secondary to retinal vein occlusion is responsible for vision loss in retinal vein occlusions, and the advent of anti-VEGF therapeutics has revolutionized the management of vascular disease in the retina.
In this chapter, we review our current understanding of retinal vein occlusions and how OCT-Angiography (OCT-A) is being used clinically in the diagnosis and management of obstructive venous vascular phenomena. The benefits of using OCT-A in the diagnosis and management of CRVO and BRVO over conventional approaches, such as Fundus Fluorescein Angiography (FFA), are discussed. The current limitations of OCT-A and recent advances in the technology are also covered here. Finally, we assess how OCT-A can play a role in the development of new therapeutics to tackle one of the major causes of vision loss worldwide.

Optical Coherence Tomography- Angiography (OCT-A) can separately detect the superficial vascular plexus and the deep vascular plexus. Paracentral acute middle maculopathy (PAMM) is an idiopathic or secondary entity to a local retinal vascular or systemic disease, characterized by capillary vascular occlusions. Some authors recognize it as a variant of acute macular neuroretinopathy (AMN). In general, the most frequent findings in the acute phase are a slight decrease in deep capillary plexus (DCP) perfusion, and hyperreflectivity of the middle layer; in the chronic phase, the findings are DCP hypoperfusion and hyporeflectivity of the middle layer.

Recently, qualitative and quantitative perfusional evaluations of vessel density (VD) and choriocapillaris flow patterns at the macular level have changed the evaluation spectrum and management of different macular pathologies. Published data on long-term macular perfusional findings and quantitative VD and flow evaluation (perfusion indices) in patients at different stages of successfully operated myopic traction maculopathy (MTM) compared with the corresponding values in normal control subjects are limited. This chapter describes the role of macular perfusion as a contributing factor to the pathogenesis of MTM.

The primary outcome measure included the long-term structural and perfusional macular status across groups. Forty-six eyes of 34 patients were included in the study group. The axial length was 29.89±1.67 mm. The postoperative follow-up period was 43±26.77 months. The preoperative BCVA was 1.29±0.54 logMAR, and the postoperative BCVA was 0.60±0.52 logMAR (P<0.05). The difference in perfusion indices across groups was statistically significant (p<0.005). Surgically resolved MTM eyes generally had a larger superficial foveal avascular zone area, lower vessel density, smaller choriocapillaris flow area (CFA), thinner central subfoveal thickness (CSFT), and more macular defects. Better functional, structural, and perfusion index outcomes were observed in highly myopic eyes that underwent early surgery. 

Rhegmatogenous retinal detachment (RRD) is the separation of the neurosensory retina from the underlying retinal pigment epithelium (RPE) and is one of the leading causes of severe vision loss when it involves the macula or proliferative vitreoretinopathy (PVR) in different stages. Optical coherence tomography (OCT) and Optical coherence tomography - angiography (OCT-A) have opened a new scenario in the investigation of macular microstructural abnormalities in RRD.

Findings in the preoperative retinal detachment structural B-scans in OCT such as ellipsoid zone (EZ)/external limiting membrane (ELM) integrity, cavities along the inner nuclear layer (INL) or outer nuclear layer (ONL), retinal height of detachment at the fovea, presence of retinal folds and subfoveal choroidal thickness may predict the functional and structural outcomes.

Structural and en-face analysis with OCT-A in RRD with PVR has demonstrated an enlarged foveal avascular zone, and changes in the flow at the superficial, intermediate and deep capillary plexus during 6 months postoperative follow up. High resolution and deep enhancing imaging OCT-A technology will provide an important role regarding the choriocapillaris and choroid and their potential correlation with visual acuity recovery.

OCT and OCT-A will provide preoperative prognostic biomarkers and adequate vascular retinochoroidal layers may influence a postoperative outcome.

The pachychoroid spectrum has various clinical manifestations. There are three major characteristics, all of which have an unknown etiology and controversial pathogenesis: pachychoroid, presence of pachyvessels at the external choroid, and inner choroidal attenuation. This study describes a patient with clinical and multimodal manifestations in the pachychoroid spectrum, in which different clinical variants are presented in both eyes simultaneously. Specifically, the patient had an acute visual loss and massive hemorrhagic maculopathy in the right eye, and a chronic decrease in visual acuity and metamorphopsia in the left eye accompanied by pigmentary changes and subretinal fluid at the geometric center of the fovea. The patient underwent a complete ophthalmological examination and multimodal imaging and was diagnosed with polypoidal choroidal vasculopathy (PCV) and pachychoroid neovasculopathy (PNV); two different manifestations of the same disease spectrum occur simultaneously.

Owing to the active nature of the disease, the patient received three doses of intravitreal antiangiogenic agents in each eye. Many different degenerative etiologies have been considered, such as pathological choroidal neovascularization due to age-related macular degeneration (AMD) and pachychoroid spectrum. Evaluation of the choroid vasculature using swept-source optical coherent tomography (SS-OCT) and OCT angiography (OCT-A) revealed the origin of the disease to be idiopathic. PCV and PNV are considered to represent a single end-stage of the pachychoroid spectrum with different manifestations; the former presents with aneurysmatic characteristics, whereas the latter lacks this anomaly. 

Optical coherence tomography angiography (OCT-A) is an emerging technology that captures flow motion within the retinal vasculature to produce angiograms. Compared to dye-based angiography techniques, OCTA is a noninvasive and fast method that enables detailed visualization of the vasculature, which is not easily observable using previously available techniques. Over the past decade, OCT-A has been used to characterize the pathological features of choroidal neovascularization (CNV) associated with several retinal diseases, including neovascular age-related macular degeneration (AMD). In eyes at risk of developing CNV, OCT-A has demonstrated the capability to detect subclinical signs of neovascularization (NV) that may enable early treatment and better visual outcomes. Various CNV conditions are now routinely treated with intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF). OCT-A was used to identify the characteristics of CNV at various stages, before and after anti-VEGF therapy. Although preliminary, OCT-A has demonstrated the potential to help guide treatment decisions in CNV cases that respond differently to anti-VEGF therapy.

Despite its multiple advantages and applications, the clinical use of OCT-A remains limited. OCT-A has several limitations, including visualization of a small area, the presence of artifacts, and results that are challenging to interpret. However, OCTA technology continues to advance as some of the early limitations have been resolved. Overall, OCT-A promises to be a significant step forward in our current ability to visualize pathological CNV, and has the potential to improve both the diagnosis and management of a variety of retinal diseases.

Despite the abundant literature on management options for noncomplicated macula-off rhegmatogenous retinal detachment (RRD) repair, the role of the corresponding long-term postoperative macular perfusion indices and their correlation with the postoperative epiretinal membrane (ERM) formation remain vaguely understood. In this chapter, we have analyzed the incidence of postoperative ERM proliferation and the differences in the corresponding postoperative macular perfusion indices in patients who underwent two well-known surgical approaches for noncomplicated macula-off RRD. Postoperative microstructural and perfusional findings were compared, and their correlation with best-corrected visual acuity (BCVA), postoperatively, was assessed. Two study groups based on the surgical procedures performed for noncomplicated macula-off RRD were analyzed. The postoperative incidence of ERM was 23.2% and 23.63% in the buckle vitrectomy groups, respectively (p>0.05). The RRD recurrence rates in the buckle and vitrectomy groups were 8.8% and 1.82%, respectively (p>0.001). The mean BCVA values before ERM removal in the buckle and vitrectomy groups were 0.40±0.33 log of the minimum angle of resolution (logMAR) and 0.47±0.19 logMAR, respectively (p<0.05). The final mean postoperative BCVA in the buckle and vitrectomy groups were 0.43±0.14 logMAR and 0.28±0.19 logMAR, respectively (p<0.05). When the retinal perfusional indices of the buckle and vitrectomy groups were compared with the normal control group, all the perfusional indices differed significantly (p<0.01). 

The eye is a window to the brain because of its inherent connection to the central nervous system (CNS). Several brain disorders manifest as ophthalmic abnormalities and can be detected through a detailed assessment of the eyes. In the last decade, extensive evaluation of retinal microvascular changes using optical coherence tomography angiography (OCT-A) has been performed for several diseases, such as Parkinson's disease, Alzheimer's disease, and systemic lupus erythematosus. Although the results from the available studies are conflicting (mainly due to heterogeneous study populations), they agree on the applicability of this technology for the early identification of these diseases. This chapter summarizes the OCT-A screening and monitoring uses for these diseases and hypotheses for the potential identification of disease characteristics.

The retina requires a large blood supply to cope with the metabolic demands of the tissue, so it is vulnerable to hypoxia when the arterial blood flow is obstructed. Retinal artery occlusions are not common, but they can cause severe vision loss and may be indicative of cardiovascular disorders, such as cerebral stroke and ischemic heart disease. The central retinal artery arises from the ophthalmic artery and its branches supply blood to the inner retina via the superficial capillary plexus. Central retinal artery occlusion (CRAO) is characterized by an obstruction to the central retinal artery that often presents with severe vision loss and a poor prognosis. Branch retinal artery occlusion (BRAO) is defined by a blockage of a branch of the central retinal artery, which typically has a good prognosis if visual acuity is 20/40 or better on presentation. Optical coherence tomography-angiography (OCT-A) is a rapid, highresolution imaging technique that can visualize the microvasculature of the retinal layers, including the superficial and deep capillary plexuses.
Therefore, it is possible to determine the microvascular changes that occur following retinal artery occlusions, and before and after potential therapies that are being actively researched. Therapies under investigation for the treatment of CRAO and BRAO include hyperbaric oxygen, fibrinolysis, and embolysis with laser therapy. In this chapter, the capabilities of OCT-A imaging to visualize and quantify retinal microvascular changes following CRAO and BRAO are assessed. Moreover, the use of OCT-A to understand the benefit of potential therapies is reviewed. 

Choroidal neovascularization (CNV) is characterized by the growth of new blood vessels from the choroid to the subretinal pigment epithelium, subretinal space, or both. Newer diagnostic and treatment methods, such as, Optical Coherence Tomography Angiography and anti-vascular Endothelial Growth Factors, are becoming increasingly effective for CNV diagnosis and management, respectively. Anti-VEGF (Ranibizumab, Bevacizumab, and Aflibercept) treatment has become the first-line treatment for CNV and has replaced other methods, such as laser photocoagulation and photodynamic therapy. The current literature has established similar safety and efficacy of the three drugs (Ranibizumab, Bevacizumab, and Aflibercept) in the treatment of CNV, especially when the visual loss is mild. However, Aflibercept has been reported to result in slightly better long-term visual outcomes. Newer molecules such as Brolucizumab and Faricimab show the potential to decrease the treatment frequency and increase efficacy due to better penetration and by increasing drug concentration in the retina, addressing the limitations of the currently available drug options.
However, their investigation was in the early stages and may have taken some time before being seen in the clinic. Innovative methods for continuous drug delivery to the vitreous through the use of dedicated ocular implants filled with anti-VEGF drugs for controlled release (port delivery systems) have also shown promising results in clinical trials. The development of this technique is expected to reduce the total number of injections and maintain stable vision. Different clinical trial protocols across studies remain an issue in addressing research questions related to dosing frequency and gaps.

The human retina is supplied by an extensive network of capillaries, where healthy blood flow to various parts of the retina, particularly the macula, is vital for visual functions. Any obstruction in blood flow, known as retinal vein occlusion (RVO), can reduce venous blood return. RVO can occur either at a central location (called central retinal vein occlusion [CRVO]) or a peripheral location (branch vein occlusion [BRVO]). Various techniques have been used to investigate blood flow to the retina and analyze different factors that may impact retinal blood flow. Optical coherence tomographic angiography (OCT-A) has emerged as one of the best methods, with several studies demonstrating its use to investigate changes in blood perfusion status, hemorrhage from blood vessels, and the presence of edema. Some studies have demonstrated that OCT-A is superior to other techniques.
Macular edema secondary to RVO is the most common complication that may affect visual acuity and lead to vision loss if left untreated. Several qualitative and quantitative changes caused by RVO can be detected using OCT-A, including vascular blood perfusion and vascular density. Several treatment options have been used to treat macular edema secondary to RVO and other complications. Laser photocoagulation therapy has been used extensively in the past with mixed outcomes. Glucocorticoids, especially dexamethasone (Ozurdex®), have also been used to treat macular edema secondary to RVO. Currently, anti-vascular endothelial growth factor (VEGF) agents are the gold standard for treating RVO. Ranibizumab and aflibercept are approved for the treatment of macular edema secondary to RVO, with faricimab expected to soon be approved.