Ocular manifestations of a rare congenital heart defect: Advanced glaucoma and retinal vein occlusion associated with double-chambered right ventricle

Abstract

Purpose

To present a case of advanced glaucoma and central retinal vein occlusion (CRVO) linked to elevated episcleral venous pressure (ESVP) in the setting of double-chambered right ventricle (DCRV), a rare congenital cardiac anomaly.

Observation

A 40-year-old man presented with advanced bilateral glaucoma and longstanding light perception vision in the right eye due to CRVO and neovascular glaucoma. Examination revealed elevated intraocular pressures (IOP) and bilateral corkscrew episcleral vessels, consistent with elevated ESVP. Systemic workup uncovered erythrocytosis and an undiagnosed DCRV with severe right ventricular outflow tract obstruction. Despite medical therapy, progressive glaucoma in the left eye required surgical intervention with Xen gel stent implantation. Initial IOP control was achieved but later increased due to iris incarceration and bleb fibrosis, requiring surgical revision and implantation of a new Xen stent. The patient also underwent cardiac surgery to correct the congenital defect. After cardiac surgery and new Xen implantation, IOP stabilized at 10–12 mmHg without topical medications.

Conclusion & importance

Congenital cardiac anomalies such as DCRV can result in secondary glaucoma and CRVO. However, reports of ocular complications in patients with congenital heart disease remain limited, warranting heightened clinical awareness. This case illustrates the importance of evaluating systemic and cardiac causes in patients presenting with glaucoma secondary to elevated ESVP. Appropriate investigation can reveal life-altering diagnoses as seen in our patient where a cardiac anomaly was identified and necessitated surgical correction. Glaucoma management in this context is particularly challenging and this case illustrates the unique limitations and important considerations involved in both medical and surgical treatments.

1. Introduction

Glaucoma can develop secondary to elevated episcleral venous pressure (ESVP) caused by impaired ocular venous drainage. Potential causes include orbital pathology (e.g. thyroid eye disease or orbital masses), carotid-cavernous fistulas, cavernous sinus thrombosis, orbital varix, Sturge-Weber syndrome, superior vena cava syndrome, and idiopathic (Radius-Maumenee Syndrome)0.1, 2, 3, 4, 5 Although less commonly recognized, cardiac anomalies also can cause secondary glaucoma and should be considered in the differential diagnosis for ESVP, since early detection can be life-altering.^6,7

In this case report, we present a young adult with an undiagnosed congenital heart defect, double-chambered right ventricle (DCRV), who initially presented to ophthalmology with advanced secondary glaucoma in both eyes due to elevated ESVP, as well as blindness in the right eye (OD) from central retinal vein occlusion (CRVO) and neovascular glaucoma. This report emphasizes key differential diagnoses and investigations to consider when evaluating secondary glaucoma and retinal vein occlusion (RVO), which, in our case, led to the life-altering diagnosis of congenital heart disease. We also discuss the unique challenges involved in medically or surgically managing secondary glaucoma caused by elevated ESVP.

2. Case report

A 40-year-old Jamaican male with a past medical history of hypertension, gout, and a 13.5 pack-year smoking history was urgently referred to ophthalmology by an optometrist for elevated intraocular pressures (IOP) in both eyes (33 mmHg OD and 35 mmHg left eye (OS), not on any eyedrops) and neovascularization of the iris (NVI) OD. He had been seen by an optometrist 2 weeks prior to his initial ophthalmology consultation. He was started on a combination IOP-lowering drop (0.004% travoprost, 0.5% timolol) nightly in both eyes. He reported that his previous optometrist retired, and that he had been lost to follow up during the COVID-19 disease pandemic. His previous ocular history included CRVO OD (at the age of 34 years) with longstanding light perception (LP) vision; no systemic work-up was performed for the CRVO at his initial presentation at age 34. At presentation, OD vision was LP and had a 3+ relative afferent pupillary defect. The uncorrected vision was 20/20 OS. IOP was 45 mmHg OD and 34 mmHg OS. Anterior segment examination OD revealed dilated corkscrew episcleral vessels, mild NVI, and dense white cataract (Fig. 1A). He had dilated corkscrew episcleral vessels and dilated engorged iris vessels but no NVI OS. In both eyes, the anterior chambers were deep and there was no inflammation. The cornea was clear in both eyes. Gonioscopy showed that the angle was closed OD with 360 degrees of peripheral anterior synechiae. The angle was open OS with no evidence of neovascularization of the angle (NVA). There was no proptosis, extraocular movements were normal, and cranial nerve III-VII exams were normal bilaterally.

Fig. 1.

A 40-year-old male with double chamber right ventricle presented with bilateral glaucoma and a blind right eye secondary to central retinal vein occlusion. A) External photograph taken at presentation of both eyes showing dilated corkscrew episcleral vessels (yellow arrows) and a dense white cataract in the right eye (OD). B) A colour fundus photo (Optos camera) showing a cupped left optic disc (cup-to-disc ratio of 0.8). C) Optical coherence tomography (OCT) of the macula shows normal retina structures in the left eye (OS). The left panel shows the en-face infrared photograph of the fundus and the green lines show where the OCT scans were captured; the green arrow shows the location of the OCT scan displayed in the right panel. D) The left panel shows global thinning of the retinal nerve fiber layer (RNFL) OS as measured by OCT (CIRRUS 6000, Zeiss). The right panel quantifies the RNFL thickness at different areas around the optic disc (INF = inferior; NAS = nasal, SUP = superior; TEMP = temporal); there is significant superior and inferior RNFL thinning and the average RNFL thickness measured 64um. E) Humphery visual field (24-2C) shows an inferior arcuate defect OS. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

The fundus view OD was obscured due to a dense cataract. A B-scan ultrasound revealed a vitreous hemorrhage and macular membranes OD, likely resulting from neovascularization due to a previous CRVO. The retina and vessels OS appeared normal on dilated examination; however, the optic disc had a cup-to-disc ratio of 0.8 (Fig. 1B). Optical coherence tomography (OCT) of the macula showed normal retinal structures OS (Fig. 1C). OCT of the optic disc showed thinning of the superior and inferior peripapillary retinal nerve fiber layer (RNFL) OS (Fig. 1D). Visual field testing revealed an inferior arcuate defect OS (Fig. 1E).

Overall, his clinical presentation was consistent with glaucoma secondary to elevated ESVP in both eyes, along with neovascular glaucoma in his blind right eye. A computerized tomography (CT) of the head and a magnetic resonance imaging (MRI) of the brain and orbits with contrast was performed to exclude potential serious causes of elevated ESVP. The results were normal, showing no evidence of a carotid-cavernous fistula, orbital varix, or compressive mass lesion in the suprasellar region or orbits. Considering the patient's history of CRVO at a young age, bloodwork was performed to evaluate markers for hypercoagulability, hyperviscosity, and inflammation. Results showed marked erythrocytosis with a hemoglobin of 194 g/ml (range 125-170g/ml); the remaining blood work was normal including erythrocyte sedimentation rate, C-reactive protein, Protein C/S, international normalized ratio (INR), cardiolipin antibodies, B2-glycoprotein 1 antibodies, complement factor 3 & 4, antinuclear antibody and double-stranded deoxyribonucleic acid. He was promptly referred to the Internal Medicine team for further evaluation of erythrocytosis with concerns for hematological malignancies (e.g. polycythemia vera, or myeloproliferative neoplasms), cyanotic heart disease, chronic lung disease, or erythropoietin secreting renal tumor. Investigations were negative for hematological or renal malignancies, but echocardiogram revealed an anomalous band of muscular fibers across the right ventricle. Cardiology diagnosed him with DCRV with associated bi-directional shunting through a ventricular septal defect, severe right ventricle hypertrophy, early signs of right heart failure, and right ventricle outflow obstruction. His erythrocytosis was a compensatory response to central cyanosis due to his congenital cardiac anomaly.

The patient's IOP was managed by a glaucoma specialist. Given no visual potential OD, the goal was simply to maintain comfortable IOP. At initial presentation, he reported having mild discomfort/pain OD which improved after starting eye drops (travoprost/timolol). Given the minimal NVI and the patient's comfort, the retina specialist opted not to start anti-vascular endothelial growth factor therapy. Treatment efforts were placed to minimize glaucoma progression OS. In addition to his travoprost/timolol drop, he was started on brimonidine/brinzolamide drops three times daily OS, and oral acetazolamide 250 mg twice daily. Topical apraclonidine 0.5% was added to both eyes due to its potential effects on decreasing ESVP.⁸ Acetazolamide was discontinued after two weeks as the patient experienced side effects of fatigue. Despite maximum tolerated medical therapy, IOP OS remained in the range of 24-30 mmHg and repeat visual field testing revealed glaucoma progression. To further manage the IOP, a minimally invasive glaucoma filtering surgery was carried out with the implantation of a Xen 63 gel stent using an ab-externo approach with mitomycin C (0.2 mg/mL, total of 0.2mL injected); this approach was chosen by the surgeon to minimize the risk of developing a suprachoroidal hemorrhage in the setting of elevated ESVP. This external technique allowed for the creation of a smaller scleral tunnel using a 30-gauge needle, rather than using the manufacturer's preloaded 27-gauge injector. This helps minimizes peritubular flow thereby reducing the risk of early postoperative hypotony.⁹ At 1-day post-op, the IOP was 12 mmHg OS, off all glaucoma drops with a good elevated, diffuse bleb. At 1-month post-surgery, the IOP remained stable (12-14 mmHg) off all drops OS. Unfortunately, the IOP gradually increased over the following two months due to iris obstructing the Xen which necessitated surgical revision. Trimming of the internal end of the Xen was done ∼3 months after the original surgery. The IOP decreased from 35 mmHg (on two classes of glaucoma drops) to 11 mmHg (off all glaucoma medications) with reformation of a diffuse bleb. In subsequent months, the bleb began to fibrose and IOP gradually elevated into the low-to-mid 20's requiring IOP lowering drops (at this time he was on latanoprostene-bunod once nightly in both eyes and timolol twice a day in both eyes). He also underwent surgical correction of his cardiac structural defects (∼9 months after his initial Xen surgery) and recovered without any postoperative complications. Three months after his cardiac surgery, IOP remained in the low-to-mid 20s OS on latanoprostene-bunod once nightly and timolol twice daily. While trying to medically manage IOP, surgical intervention was discussed however, given the patient's monocular status, he was hesitant to proceed with more surgery. With close follow-up, persistently elevated IOP (remaining in low-to-mid 20s) and some evidence suggesting possible disease progression, the patient agreed to open XEN revision surgery. About 9 months after cardiac surgery, an open revision was done and poor flow was noted coming from the Xen. Thus, the decision was made to implant a new Xen 63 stent with careful positioning of the new Xen to avoid future iris obstruction. After the new implant, IOP was well controlled (10-12 mmHg ∼2 weeks after the surgery) off all glaucoma drops with a good bleb; the Xen was well positioned above the iris, in the mid-anterior chamber. The patient also developed a visually significant cataract OS which was operated on 4 months after the new Xen implant. About, 7 months after the new Xen implant (3 months after the cataract surgery), IOP was well controlled (13 mmHg) off all glaucoma drops and uncorrected distance visual acuity of 20/20; visual fields were stable over the past ∼12 months. There was good bleb morphology and, the episcleral vessel tortuosity remained largely unchanged (Fig. 2).

Fig. 2.

External eye photograph of a 43-year-old male with double chamber right ventricle 33 months after initial presentation with bilateral glaucoma and a blind right eye secondary to central retinal vein occlusion. A) External photograph of both eyes (OD = right eye, OS = left eye) showing that the dilated corkscrew episcleral vessels remained unchanged 16 months after cardiac surgery for congenital heart defect. B) The left panel shows the bleb under diffuse illumination demonstrating its overall morphology at 7 months following the new Xen 63 implantation OS. The right panel highlights the bleb height using a narrow slit-beam. The Indiana bleb grade was height = grade 2, extent = 2-3 clock hours, vascularity = grade 2, seidel = negative.

3. Discussion

DCRV is a rare congenital cardiac defect in which the right ventricle is divided into high- and low-pressure chambers for which surgical correction is gold standard treatment.¹⁰ Ocular manifestations in patients with DCRV has not been described previously. In general, there is limited literature describing the ocular complications associated with cardiac defects. Cardiac defects such as Tetralogy of Fallot, atrial septal defects and Eisenmenger syndrome have been described to cause CRVO.^6,7,11,12 Here we showed that DCRV can result in glaucoma and CRVO. Glaucoma can occur secondary to two mechanisms: (1) elevated ESVP and (2) obstruction of trabecular meshwork due to neovascularization precipitated by RVO.

Schlemm's canal drains aqueous humor into veins, thus any downstream venous obstruction, such as superior vena cava syndrome,^1,3,13,14 can lead to elevated ESVP. Likewise, chronic right ventricle outflow obstruction likely resulted in elevated ESVP in our patient. While cardiac surgery to correct the ventricular outflow obstruction may help improve ESVP, we theorize that this improvement could take months to years, if at all, due to chronic vascular remodeling. While we could not identify studies directly quantifying episcleral venous remodeling, non-ocular data suggested that vascular remodeling (e.g. vessel wall thickening) can persist many months after venous obstruction has been relieved.¹⁵ For example, studies of post-thrombotic vein wall remodeling in humans show that vessel remodeling can occurs up to 6 months after thrombus resolution.¹⁵ In infants, we hypothesize earlier cardiac surgery may allow more rapid improvement in ESVP, whereas in adults, long-standing vascular remodeling may limit the speed or extent of reversal. In our patient, the dilated and tortuous episcleral vessels remained largely unchanged approximately 16 months after cardiac surgery (Fig. 2A). This has clinical relevance since glaucoma surgery may be postponed in infants who are scheduled to undergo cardiac surgery.

The presence of the DCRV creates a bi-directional shunt which results in poor cardiac outflow and central cyanosis. This stimulates compensatory erythrocytosis, increasing blood viscosity and creating a hypercoagulable state. Hyperviscosity from erythrocytosis, together with venous congestion secondary to right-sided heart failure, likely contributed to the development of CRVO.^12,16,17 Additional risk factors such as hypertension and a history of smoking, contributed to the development of CRVO in our patient.¹⁶ As a result of retinal ischemia, the patient developed neovascular glaucoma. Additionally, erythrocytosis may contribute to glaucomatous optic neuropathy through impaired ocular perfusion. Elevated hematocrit increases blood viscosity leading to venous stasis (a hypercoagulable state) and delayed blood flow that reduces oxygen delivery to the optic nerve. Poor optic nerve perfusion has been linked to glaucoma development and progression, as seen in normal tension glaucoma where nocturnal hypotension is associated disease progression.¹⁸ Similarly, in erythrocytosis, hyperviscosity-related vascular compromise may lower perfusion pressure at the optic disc resulting in glaucomatous damage even without markedly elevated IOP.

Although treatment of erythrocytosis was not undertaken prior to cardiac surgery in our patient, it remains an important consideration in similar cases and underscores the need to evaluate systemic hematologic abnormalities in young patients presenting with CRVO or neovascular glaucoma.

Unfortunately, the patient did not undergo an adequate evaluation for CRVO at the time of his initial presentation many years ago. This case underscores the importance of performing a comprehensive ocular and systemic work-up in patients with CRVO, particularly in younger individuals or in cases with atypical features such as bilateral involvement or evidence of inflammatory vasculitis.¹⁹ Ocular assessment consists of a complete eye examination with IOP, slit-lamp evaluation, gonioscopy to detect iris or angle neovascularization, and dilated fundus examination. In addition, fluorescein angiography is valuable for evaluating retinal perfusion whereas OCT is important for assessing macular edema.²⁰ Key systemic evaluation includes measuring blood pressure and targeted laboratory testing to assess for vascular risk factors including blood glucose, complete blood count, and lipid profile.²⁰ In younger patients with CRVO (typically under 50 years of age), the diagnostic evaluation should rule out coagulopathies and systemic causes of hypercoagulability (e.g., multiple myeloma, Waldenström macroglobulinemia, or leukemia).^19,21 Some recommended investigations include INR, activated partial thromboplastin time, antiphospholipid antibodies, Factor V Leiden mutation, Protein C and S deficiency, antithrombin deficiency, homocysteine, erythrocyte sedimentation rate and plasma protein electrophoresis.^20,21 These patients require frequent monitoring (monthly follow-up for the first 6 months and then every 3 months for 1 year) for the development of anterior segment neovascularization and neovascular glaucoma.^20,21

Managing glaucoma in the setting of elevated ESVP presents unique challenges and there is no established consensus on the optimal approach to treatment. Selective laser trabeculoplasty (SLT) and topical medications, which aim to enhance trabecular or uveoscleral outflow, are often not as effective in patients with elevated ESVP. Some studies have suggested that topical agents such as apraclonidine and Rho-kinase inhibitors can improve episcleral venous outflow thereby lowering ESVP.⁸

Achieving meaningful IOP reduction in patients with elevated ESVP often requires filtering surgery such as trabeculectomy, though such procedures carry a higher risk of complications such as uveal effusion and suprachoroidal hemorrhage.^1,22 Minimally invasive procedures such as microshunt implantation help reduce these risks by lowering the risk of hypotony.^23,24 This case showed that Xen 63 stent can be an effective and minimally invasive option for IOP reduction in the setting of elevated ESVP.

4. Conclusion

This case describes the presentation and management of glaucoma and RVO in a patient with a rare congenital cardiac defect, DCRV.

CRediT authorship contribution statement

Jo-Ann Khoury: Writing – review & editing, Writing – original draft, Data curation. Pushpinder Kanda: Writing – review & editing, Writing – original draft, Data curation, Conceptualization. Hertek Gill: Writing – review & editing, Writing – original draft, Data curation. Tushar Dave: Writing – review & editing, Writing – original draft, Data curation. Garfield Miller: Writing – review & editing, Supervision, Conceptualization.

Patient consent

Informed consent was obtained from the patient to publication of this case report and the accompanying images.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.