Advanced Coats' disease treated with intravitreal brolucizumab combined with laser photocoagulation.

PURPOSE: To report the first use the intravitreal anti-VEGF brolucizumab for the treatment of macular exudates and edema in a patient with Coats' disease. OBSERVATIONS: A 9-year-old boy was referred with a decrease in vision in the right eye. Visual acuity was 20/400 OD on presentation, and examination was remarkable for peripheral telangiectasias, exudates, microaneurysms, macular edema, and an inferior exudative retinal detachment. A diagnosis of Stage 3A2 Coats' disease was made, and the patient was treated with intravitreal bevacizumab as well as peripheral diode laser. However, on follow up, there was persistence of subretinal fluid accompanied by a decrease in visual acuity. The patient was then treated with intravitreal brolucizumab. Post injection visual and anatomical improvements were significant with complete resolution of macular edema within two weeks. Throughout the 5 months of follow up, there has been no re-accumulation of fluid and no further required therapy. CONCLUSIONS AND IMPORTANCE: Intravitreal brolucizumab was effective for the treatment of retinal edema and exudates in Coats' disease.

Introduction

Coats' disease, first described in 1908, is characterized by peripheral vascular ectasia, aneurysms, and exudation. Historically, the main treatment included repetitive laser photocoagulation to areas of nonperfusion and telangiectasias. Recent studies have demonstrated upregulation of VEGF in patients with Coats’ disease, and this has prompted interest in intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy as an adjuvant to laser photocoagulation., Multiple reports have shown safety and efficacy of intravitreal bevacizumab, ranibizumab, conbercept, and aflibercept in combination with ablative therapies.,

Brolucizumab is the most recently U.S. Food and Drug Administration (FDA) approved anti-VEGF agent for intraocular use. Brolucizumab inhibits all isoforms of VEGF A with a human single chain antibody fragment scaffold. It is the smallest available anti-VEGF molecule, allowing for an increase in molar concentration, and consequently, a potential for an improved effect duration., Similar to other anti-VEGF agents, it may provide therapeutic benefits in patients with Coats’ disease.

In this case, we report the first use of intravitreal brolucizumab combined with laser photocoagulation in a pediatric patient for the treatment of advanced recalcitrant Stage 3A2 Coats’ disease with complete and maintained resolution of subretinal fluid after a single treatment.

Case

A 9-year-old male, without systemic disease, was referred to our clinic due to painless visual loss in the right eye (OD) of 4 months duration. Best-corrected visual acuity was 20/400 OD and 20/20 left eye (OS). Intraocular pressures were 14 in both eyes (OU). A complete ophthalmologic exam was performed. Anterior segment examination was unremarkable OU. Pupils were equally round and equally reactive to light without evidence of afferent pupillary defect. No evidence of vitreous cells was present OU. Funduscopic examination OD was remarkable for peripheral telangiectasias, exudates, microaneurysms, macular edema, and an inferior exudative retinal detachment. (Fig. 1). Funduscopic examination OS was remarkable for avascular peripheral retina. Optical coherence tomography OD demonstrated intraretinal hard exudates, intraretinal fluid, and an exudative retinal detachment (Fig. 2). A diagnosis of Stage 3A2 Coats’ disease was made.

Fig. 1

Fundus photo of the right eye demonstrating dense sub-retinal exudates concentrated in the macula.

Fig. 2

Optical coherence tomography with intraretinal hard exudates, intraretinal fluid, and an exudative retinal detachment.

Four weeks after initial presentation the patient underwent examination under anesthesia with diode laser ablation of all telangiectasias and intravitreal bevacizumab (2.5mg/0.1mL) therapy. Reevaluation in the clinic 1 month after initial therapy showed persistent subretinal fluid and decrease in visual acuity to counting fingers at 1 feet OD.

Due to decrease in visual acuity, the patient was then taken to the operating room and additional laser was applied to skip areas. Concomitant intravitreal injection of brolucizumab (6mg/0.05mL) was undertaken. Two weeks after therapy the patient had complete resolution of sub-foveal fluid (Fig. 3) and visual acuity improvement to 20/200. Most recently, the patient has remained with stable visual acuity and without subretinal fluid re-accumulation or vascular leakage for 21 weeks (Fig. 4), avoiding the need for further therapy.

Fig. 3

Optical coherence tomography two weeks post intravitreal injection with brolucizumab showing complete resolution of sub-foveal fluid.

Fig. 4

Late phase fluorescein angiography 21 weeks after intravitreal brolucizumab shows complete resolution of vascular leakage and macular edema.

Discussion

Historically, eyes with Coats' disease have carried a poor visual and anatomical prognosis. Some authors reported enucleation in over 10% of cases. However, the availability of intraoperative pediatric fluorescein angiography, indirect laser photocoagulation and anti-VEGF intravitreal injection has drastically changed the outcomes associated with this condition. This has created a shift in goals from globe preservation to visual function. Although there continues to be no FDA-approved pharmacologic treatment for Coats’ disease, publications have demonstrated subretinal fluid reduction after intravitreal anti-VEGF. Initial treatment in this case was performed with intravitreal bevacizumab in combination with peripheral vascular ablation. However, due to recalcitrant subretinal fluid and decrease in visual acuity an alternate anti-VEGF agent was delivered.

Brolucizumab is the newest-in-class anti-VEGF agent for neovascular age related macular degeneration. Two pivotal phase 3 trials, HAWK and HARRIER, demonstrated non-inferiority of intravitreal brolucizumab compared to aflibercept at 8 weeks post therapy with 50% of patients maintaining the visual and anatomical outcomes at 12 weeks In this case, there was a dramatic response to brolucizumab with complete resolution of the subretinal exudates within two weeks. Although it is possible that the initial bevacizumab treatment had some marginal additive effects, the acute improvement in visual acuity and decrease in subretinal fluid suggests greater efficacy of brolucizumab. In addition, the exudation associated with Coats' disease frequently recurs after anti- VEGF. However, in this instance, there has been no recurrence thus far with over 21 weeks of follow up. It is possible that brolucizumab may have superior therapeutic effects for Coats’ disease. Recent reports have noted intraocular inflammation and occlusive vasculitis in approximately 1 in 1000 injections and was included within the FDA evaluation of brolocizumab during HAWK and HARRIER. These potential adverse events have focused our informed consent and targeted our use of brolocizumab to patients who have failed existing anti-VEGF treatments.

Post-enucleation histologic specimens have demonstrated subretinal and intraretinal lipid laden macrophages as well as giant cell reactions surrounding the cholesterol crystals., This suggests that Coats' disease has an association with the inflammatory cascade. Interest in modulating this response has prompted multiple authors to perform intravitreal and sub-Tenon triamcinolone acetonide with positive visual and anatomical outcomes.,, Fortunately, in this case, there were no signs of intraocular inflammation or vasculitis noted post treatment. Further studies and data are required to assess the safety and efficacy of this medication in the pediatric population, and, for Coats’ disease.

Several limitations are present in this case including the precise understanding of the effects of intravitreal brolucizumab in the final outcome. Since the treatment of Coats' disease is complex often requiring repetitive multimodal therapies, some additive effects may have been present. In this case, the acute resolution of subretinal fluid and improvement in vision suggests a positive effect from intravitreal brolucizumab. Future prospective studies comparing multiple anti-VEGF agents combined with laser photocoagulation for Coats’ disease are needed.

Conclusion

This case demonstrates the first use of intravitreal brolucizumab in combination with laser photocoagulation for the treatment of Coats’ disease. A favorable response was achieved with a single treatment with complete resolution of subretinal fluid and exudation.

Patient consent

Consent was obtained from the patient before the study and publication of the case report.

Funding

No funding or grant support

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.