Levels of cytokines in the aqueous humor guided treatment of refractory macular edema in adult-onset coats’ disease

A 25-year-old man, without previous medical history, was presented to our eye clinic with decreased visual acuity in the left eye for 3 months. The best corrected visual acuity (BCVA) was 0.3 in the left eye and 1.0 in the right eye, with normal intraocular pressures. A massive intraretinal lipid accumulation with overlying vascular telangiectasis and hemorrhages was observed in the left eye (Figs. 1 and 2a). Fluorescein angiogram (FFA) (Retinal Camera, TRC-50DX, Topcon Corporation, Tokyo, Japan) revealed early hyperfluorescence of telangiectatic bulbs in the temporal regions, and hypofluorescence consistent with the subretinal exudates in the left eye. Optical coherence tomography (OCT) (CirrusHD-OCT 5000, Cail Zeiss Meditec, Inc, Clifornia USA) showed macular edema in his left eye with a foveal thickness of 802 μm. A diagnosis of adult-onset Coats’ disease was made. Examination of his right eye was unremarkable. Intraocular injection of an anti-VEGF drug (Conbercept) was performed. Before injection, the aqueous humor was removed and the levels of VEGF and inflammatory cytokines were measured. The result showed a normal VEGF level and increased Interleukin (IL) -8 (Table 1). At 1 week after the first injection, the macular edema was alleviated (Fig. 2b), with an increased BCVA of 0.5. However, after 1 month, BCVA decreased again with recurrent macular edema (Fig. 2c). A second injection of anti-VEGF was administrated and again the aqueous humor was acquired before injection. The level of VEGF was low and the level of IL-8 and VACM in the aqueous humor had increased (Table 1). Macular edema remained at this time, and laser coagulation was given at 3 weeks after injection. At 1 month after the second injection, BCVA dropped to 0.3. In consideration of the aqueous humor cytokine concentrations, treatment switched to intravitreal dexamethasone implant (Ozurdex®) (Allergan, Inc., Irvine, Calif., USA). Then the macular edema decreased dramatically (Fig. 2d) and BCVA increased to 0.6 at 2 weeks after injection. No further recurrence of macular edema was noted during 12 weeks of follow-up. Intraocular pressure was elevated at 10 weeks after injection (29 mmHg). After cartiolol hydrochloride eye drops were administrated 2 times a day, the IOP reduced to a normal level. No other adverse effect of the steroid was observed during the course of treatment and follow-up.

A 40-year-old man with 15 months history of macular edema related to Coats’ disease and progressive vison loss in his left eye within 4 weeks was admitted. BCVA was 1.0 in his right eye and 0.2 in his left eye. Subretinal lipid exudates in the temporal and nasal retina with local vascular telangiectasis was observed in the left eye (Fig. 4a). A fluorescein angiogram (FFA) revealed hyperfluorescence of the telangiectatic bulbs, and leaking vessels in the temporal and nasal regions (Fig. 3a, b). OCT showed increased macular thickness, cystoid edema and mild epiretinal membrane. (Fig. 3c). A diagnosis of adult-onset Coats’ disease was made. Before he presented to our clinic, he had received 11 intraocular injections of an anti-VEGF drug (Conbercept) and five laser treatments. Initially, he responded well to anti-VEGF drugs; however, there was no improvement after the final injection (Fig. 3d). When he presented to our clinic, he was treated with another anti-VEGF drug via intraocular injection (Aflibercept) and aqueous humor was obtained before the injection. Aqueous humor cytokine concentrations detection showed that VEGF was lower than normal, while VACM, IL-6 and IL-8 were at a very high level (Table 1). At 1 week after injection, macular thickness decreased from 727 μm to 459 μm (Fig. 3d, e); however, it increased to 490 μm again after 2 weeks (Fig. 3f). Although epiretinal membrane may be also related to the recurrence of macular edema and may influence the cytokine levels. In consideration of the high inflammatory factors and lower VEGF level, an intraocular steroid (Ozurdex®) injection was administrated. At 10 days after injection, the macular thickness dropped to 255 μm and BCVA increased to 0.5 (Fig. 4b, c). During 3 months of follow-up, visual acuity was stable without any further recurrence of edema.