The authors describe the clinical and anatomical correlation between mean ocular perfusion pressure (MOPP) changes and macular exudation in a 62-year-old man affected by circumscribed choroidal hemangioma (CCH) and primary open-angle glaucoma. During the 5-year follow-up, we noted an increase of the subretinal fluid (SRF) and cystoid macular edema (CME) when the intraocular pressure (IOP) was in the low teens. Optical coherence tomography scans performed during an isometric exercise revealed a transient increase of the retinal (choroidal) thickness. In the presented case, MOPP appears to play a role in SRF and CME associated with CCH. Management of the macular exudation could improve if IOP and blood pressure are considered and treated accordingly.
[Ophthalmic Surg Lasers Imaging Retina. 2019;50:e163–e165.]
Circumscribed choroidal hemangioma (CCH) is a benign vascular tumor that may be complicated by fluid leakage associated with subretinal fluid (SRF) and cystoid macular edema (CME).1 The aim of therapy is the reabsorption of the retinal fluid with treatments such as laser photocoagulation or photodynamic therapy (PDT).2 Primary-open angle glaucoma (POAG) is a chronic progressive optic neuropathy currently treated by lowering the intraocular pressure (IOP). Here we report a case of a glaucomatous patient under topical medical treatment in which we found a CCH whose associated macular exudation was unresponsive to PDT. We studied the correlation between ocular perfusion pressure (OPP) and clinical signs.
A 62-year-old man was affected by POAG in both eyes. Best-corrected visual acuity (BCVA) was 20/20, and IOP was controlled with medical treatment in both eyes. He was followed in our outpatient clinic since 2008. In 2013, he reported a rapid decrease of vision in the right eye. BCVA had decreased to 20/25. Optical coherence tomography (OCT) showed SRF and CME in the same eye. Diagnosis of CCH complicated by macular exudation was confirmed by fluorescein and indocyanine green angiography. PDT was performed in 2014 without improvement. During the 5-year follow-up, the patient was monitored for IOP and the presence of SRF and CME. IOP remained between 12 mm Hg and 20 mm Hg, and the therapy was switched from timolol to bimatoprost and later brinzolamide/timolol fixed combination was added. As IOP and blood pressure (BP) are determinants of the OPP (see legend of Figure 1 for the formula), we tested the hypothesis that the variation of the mean OPP (MOPP) correlates with exudative phenomena. Interestingly, in this case, the amount of SRF and CME was influenced by the MOPP levels.
Retinal thickness before, during, and after the hand grip exercise. (A) Optical coherence tomography (OCT) scan and thickness map obtained at rest. (B) After 2 minutes of hand grip exercise, MOPP increase resulted in an increase of the retinal thickness as shown by the differential maps (A vs. B). (C) Retinal thickness returned to baseline values (differential maps show A vs C).
MOPP: mean ocular perfusion pressure = 2/3 (mean arterial pressure − intraocular pressure), where mean arterial pressure = diastolic blood pressure + 1/3 (systolic blood pressure − diastolic blood pressure). The patient was asked to maintain 30% of his maximum hand grip strain for 2 minutes and for the duration of the OCT scans. We used the radial scan pattern centered on the fovea with a 12-mm length for each scan. Automatic segmentation was always reviewed to avoid and correct for segmentation errors.
During the 5-year follow-up, we also observed an increase of CME and SRF with IOP below 16 mm Hg on topical bimatoprost, reabsorption of exudation when IOP was above 16 mm Hg without bimatoprost, recurring exudation at low IOP without bimatoprost, and reabsorption of fluid at high IOP on bimatoprost therapy. The use of a prostaglandin analogue such as bimatoprost was reported as the cause of CME and SRF;3 however, our case seems to behave independently from the use of topical prostaglandin. To elucidate the role of MOPP on exudation, the patient was asked to perform a isometric hand grip exercise.4 OCT scans were obtained at rest, after 2 minutes of exercise, and again 20 minutes thereafter. During the exercise, we measured an increase of the retinal thickness in the area above the CCH (Figure 1).
Our observations led to the hypothesis that MOPP plays a pivotal role in the development of exudation and related vision loss. The choroid is a highly vascularized tissue and, conversely, to the retina5 it lacks metabolic control.6 Blood flow in the normal choroid manifests myogenic baroregulation to compensate for BP changes and maintain a stable choroidal blood flow (ChBF).7 Also, autonomic innervation has been demonstrated to influence ChBF.8 In this case of CCH, we observed differences in exudative activity of the tumor related to the variation of the OPP. As a matter of fact, the pathological choroid may have a disrupted baroregulation mechanism unable to compensate for changes in OPP. Thus, the increase of the OPP may augment the ChBF, and the macular exudative phenomena reflect this behavior. Between the retinal neural tissue and the choroid, there are the retinal pigment epithelium (RPE) cells that form a monolayer with the tight junction on their lateral surfaces.9 This barrier is called the outer retinal barrier and ensures isolation of the neural tissue from the choroid, allowing only a highly selective transport of substances. Moreover, RPE actively regulates the transports from the subretinal space to the blood of electrolytes and water.10 In chronic CCH, RPE is altered as shown by autofluorescence imaging and OCT. RPE may have been damaged because of chronic stress due to altered ChBF or because of the mass effect of the lesion that deforms and stretches the epithelium. Regardless of the cause of RPE damage, its dysfunction causes a break of the outer blood-retinal barrier favoring macular exudative phenomena. The hand grip isometric exercise triggers a cardiovascular response with rapid elevation of BP and mean arterial pressure. The increase of the retinal thickness corroborates the hypothesis that MOPP is correlated with macular exudation. The optimum management of CCH could be reached not only with laser treatments, but also considering the potential role of MOPP and treating BP and IOP accordingly (Figure 2). Our findings could be of help to interpret the physiopathology of CCH, correlating with other kinds of disease affecting the choroidal blood flow regulation, such as central serous chorioretinopathy.11 In this view, new studies may consider OPP modification as an approach in the management of exudative diseases.
Pathogenesis of macular exudative phenomena associated with circumscribed choroidal hemangioma. RPE = retinal pigment epithelium; MOPP = mean ocular perfusion pressure.
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