Eales’ disease with secondary coats’-like reaction: a case report

Abstract

Background

Eales’ disease is an idiopathic, inflammatory condition characterized by peripheral retinal phlebitis, distal non-perfusion, and neovascularization. Coats’ disease, on the other hand, is an idiopathic, retinal vasculopathy characterized by telangiectasia and yellowish exudation. Both diseases commonly affect males. Here, we report an atypical case of unilateral Eales’ disease with co-existing, secondary Coats’-like reaction in a 25-year-old male exhibiting unilateral retinal telangiectasia accompanied by subtle macular edema, extensive peripheral vascular sheathing, and distal non-perfusion in the absence of clinically visible exudation.

Methods

Case report.

Results

A 25-year-old male presented with painless blurring of vision in the right eye for two months. Best-corrected Snellen visual acuity was 3/60 in the affected eye, with relative afferent pupillary defect observed, and 6/9 contralaterally. Anterior segment examination was unremarkable. Right eye fundoscopy showed aneurysmal telangiectasia at the macula, 360 degrees perivascular sheathing and telangiectasia of peripheral retinal vessels. There was no exudation, neovascularization, tractional membranes, vitritis, retinitis, and choroiditis. Left eye fundus was unremarkable. Optical coherence tomography of the macula revealed disorganization and thinning of the inner retinal layers with minimal intraretinal fluid. Fundus fluorescein angiography showed leakage from the aneurysms but not from the sheathed vessels, and an enlarged foveolar avascular zone. A well-defined zone of non-perfusion and retinal vascular telangiectasia with shunts was observed. Blood investigations ruled out metabolic, infectious, haematological, and autoimmune causes. Carotid Doppler showed no stenosis, and CT angiography of the brain did not show any vascular abnormalities. In view that no cause was identified, a diagnosis of Eales’ disease with secondary Coats’-like reaction was made. Treatment consisted of FFA-guided laser photocoagulation to the areas of non-perfusion. Intavitreal anti-vascular endothelial growth factor injection was not done in view of poor visual prognosis. The condition and visual acuity remained stable during 18 months of follow-up.

Conclusion

This report highlights an atypical case of Eales’ disease with co-existing, secondary Coats’-like reaction.

Introduction

Eales’ disease is an idiopathic, inflammatory condition characterized by peripheral retinal phlebitis, distal non-perfusion, and neovascularization. It is more prevalent in the Indian subcontinent and usually affects young males in the third decade [1, 2]. Bilateral involvement is seen in 50–90% of cases, although it can be asymmetrical [3]. On the other hand, Coats’ disease is an idiopathic, retinal vasculopathy characterized by telangiectasia, vascular occlusion, and exudation. Typically, it affects males in the first decade, tends to be unilateral, and has no ethnic predilections [4, 5] However, such changes can also occur as a sequelae to primary ocular or systemic diseases, also known as “Coats’-like reaction” [6, 7]. Consequently, these secondary changes may conceal the underlying primary disease and thus, diagnosis can be challenging. Here, we report an atypical case of unilateral Eales’ disease with secondary Coats’-like reaction in a 25-year-old male exhibiting unilateral retinal telangiectasia accompanied by subtle macular edema, extensive peripheral vascular sheathing and distal non-perfusion in the absence of clinically visible exudation.

Case report

A 25-year-old healthy Malay male presented with painless blurring of vision in the right eye for two months, which he noticed after a trivial blunt injury by a cardbox. He was a regular smoker with a 4-pack year history. He was born full-term with no significant past ocular or medical history, no history of receiving radiotherapy, and his family history was non-contributory. He was never tested positive for COVID-19 prior to presentation. Relative afferent pupillary defect was observed in the right eye. The best-corrected Snellen visual acuity (VA) was 3/60 and 6/6 in the right and left eyes, respectively. There was no manifest strabismus. Anterior segment examination was unremarkable, and intraocular pressures were 14 mmHg bilaterally. Fundoscopy of the right eye revealed multiple aneurysmal dilatations at the macula with loss of foveolar reflex (Fig. 1A). There was 360-degree perivascular sheathing and telangiectatic changes involving the equatorial to peripheral retinal vessels (Fig. 1B-C). However, there was absence of venous dilatation and tortuosity, hemorrhages, exudation, vitritis, retinitis or choroiditis. The optic disc was pink with a cup-to-disc ratio of 0.4. Fundoscopy of the left eye was unremarkable (Fig. 1D). Systemic examination, including the central nervous system, was unremarkable.

Fig. 1

Fundus of the right eye. A) Multiple aneurysmal dilatations were observed at the macula with loss of foveolar reflex. B-C) Extensive perivascular sheathing and telangiectatic changes involving the equatorial and peripheral retinal vessels in all quadrants. No exudation and neovascularization were seen. D) Fundus of the left eye was unremarkable

Right eye spectral-domain optical coherence tomography (OCT) of the macula revealed disorganization of inner retinal layers, significant thinning of the inner and outer nuclear layers, minimal intraretinal fluid, and an epiretinal membrane. However, there was no retinal thickening and the external limiting membrane, ellipsoid and retinal pigment epithelium (RPE) layers remained largely unaffected (Fig. 2A). Central subfield thickness was 266 μm. OCT angiography (OCTA) revealed aneurysms and loss of juxtafoveal capillary network in the superficial, intermediate, and deep vascular complex layers (Fig. 2B-C).

Fig. 2

OCT and OCTA of the right eye macula. A) OCT revealed disorganization of inner retinal layers, thinning of the inner and outer nuclear layers, and minimal intraretinal fluid. The ellipsoid and RPE layers appeared intact. B-C) OCTA indicated presence of aneurysms and loss of juxtafoveal capillary network in the superficial and deep vascular complex layers, respectively

Right eye fundus autofluorescence showed an increased area of hypo-autofluorescence at the macula with hyper-autofluorescent stippling within. Fundus fluorescein angiography (FFA) showed no delay in the arm-to-retina or arterio-venous (AV) transit time. Early phase revealed aneurysmal dilatations of varying sizes predominantly at the posterior pole and to a lesser extent at the periphery (Fig. 3A). There was loss of juxtafoveal capillary network and an enlarged foveolar avascular zone (FAZ). In the periphery, there was a definite demarcation between perfused and non-perfused areas with vascular abnormalities (microaneurysms, vascular shunts, telangiectasia) at the junction, involving all clock hours. In the late phase, there was leakage from the aneurysms but no leakage from the sheathed vessels or neovascularization was noted (Fig. 3B). There was no hyperfluorescence of the optic disc. The left eye FA and FFA was unremarkable.

Fig. 3

Montage FFA images of the right eye. (A) Early phase showed multiple hyperfluorescent aneurysmal telangiectasia distributed in the posterior pole and periphery, with enlarged FAZ. In the periphery, a well-defined zone of distal non-perfusion and vascular abnormalities were noted. (B) Late phase demonstrated leakage from the aneurysms but not from the sheathed vessels. No neovascularization was noted

The blood pressure was within normal limits. Laboratory investigations done included full blood count, peripheral blood film, coagulation profile, fasting lipid profile, fasting blood glucose, and complement 3 and 4, which were within normal limits. Rheumatoid factor, anti-nuclear antibodies, anti-neutrophil cytoplasmic antibody, anti-beta-2 glycoprotein 1, anti-cardiolipin, lupus anticoagulant, rapid plasma reagin, tuberculin skin test, and Tuberculosis-Quantiferon assay, were negative. Imaging tests, including chest X-ray, echocardiography, and carotid Doppler ultrasonography, were unremarkable. Computed tomography angiography and venography of the brain showed no evidence of cerebral infarct, aneurysms, arteriovenous malformations, or thrombosis. A guarded visual prognosis was explained in view of the FFA and OCT macula findings. Prophylactic laser retinal photocoagulation of the peripheral avascular zones was done as patient was from outstation and could not commit to regular follow-ups. He was offered intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection, but he opted for conservative management in view of guarded prognosis. His condition remained stable throughout a follow-up period of 18 months.

Discussion

The typical findings of peripheral perivascular sheathing with distal non-perfusion in a young adult male without identifiable causes make Eales’ disease a likely diagnosis. Despite various classification systems proposed for Eales’ disease, consistency remains lacking [1, 3]. In general, three overlapping stages have been described for Eales’ disease: inflammatory, ischemic, and proliferative [1, 3]. The exact aetiology that incites the inflammation remains largely unknown, although studies have suggested possible associations with tuberculosis, hypersensitivity to tuberculoprotein, and immune-mediated systemic diseases [1,2,3]. From then on, the natural history of Eales’ disease is either circulatory stabilization or recurrent vitreous hemorrhages [3]. This case appeared to have conformed to the former as evidenced by vascular shuntings at the junction between the perfused and non-perfused zones, and the absence of neovascularization despite the presence of extensive areas of non-perfusion. However, there were some atypical features not commonly seen in Eales’ disease. Macula is usually spared primarily in Eales’ disease [3]. Similarly in this case, peripheral lesions were not seen in the macula. However, the presence of aneurysmal dilatations distributed mainly at the posterior pole with features of leakage, macular edema, and ischemia were suggestive of a secondary Coats’-like reaction. Similar findings have been reported in a few cases of occlussive vasculitis. In two such case reports, extensive yellowish exudates with marked intraretinal fluid accumulation at the macula was observed [6, 7]. However, this feature was largely absent in our case, indicating a possible spectrum of Coats’-like reaction similarly seen in primary Coats’ disease [4]. The exact aetiology of primary or secondary retinal telangiectasia is still unknown. However, these changes can be explained by a common histopathological findings of endothelium degeneration, basal membrane thickening, luminal narrowing with eventual occlusion, and pericyte dropout [8, 9]. This eventually leads to ectasia, ischemia, and exudation. These secondary changes seen in the macula are believed to be the main reason for poor visual acuity in this case.

In view that Eales’ disease is a diagnosis of exclusion, we will discuss a few possible differential diagnoses which we have systematically excluded. Tubercular retinal perivasculitis was a highly possible aetiology in view of the reported associations with Eales’ disease and the patient was from a Tuberculosis-endemic region. Singh R and colleagues reported that up to 57% cases of Eales’ disease was found to have the MPB64 gene of Mycobacterium tuberculosis detected in vitreous samples [2]. However, tubercular retinal perivasculitis is usually bilateral with presence of retinal hemorrhages, which was absent in this case [2]. Furthermore, the Mantoux test and Tuberculosis-Quatiferon assay were also negative. Mantoux-negative cases of Eales’ disease are not uncommon and have been reported in a series of case reports, further indicating the possibility of other aetiologies still undiscovered yet [2, 6]. Other infectious cause such as syphilis, and autoimmune diseases such as systemic lupus erythematosus and ANCA-associated vasculitis were excluded from negative test results. Behcet’s disease was unlikely too due to the lack of signs of inflammation in the anterior chamber and posterior segment, and is usually bilateral. A previous retinal vein occlusion was given a strong consideration in this case. However, the absence of retinal hemorrhages, collateral vessels at the disc, venous dilatation and tortuosity made this a less likely possibility. In addition, the arterio-venous transit time was not increased on FFA and hematological test results for possible underlying blood disorders such as sickle cell disease, polycythemia, and lymphoproliferative disorder, were within normal limits. Idiopathic retinal vasculitis-aneurysms-neuroretinitis (IRVAN) syndrome was excluded as the aneurysmal dilatations are usually larger and are mainly located at arterial bifurcations, with presence of neuroretinitis-like feature. Familial exudative vitreoretinopathy and retinopathy of prematurity were unlikely as well as history was non-suggestive and there was no neovascularization, exudation or tractional membranes. Cases of unilateral atypical retinitis pigmentosa had been reported, but the absence of retinal pigmentary changes, largely intact outer retinal layers, and presence of perivascular sheathing make this diagnosis improbable in this case [10, 11]. Given the lack of identifiable cause in our case, an idiopathic cause of unilateral telangiectasia such as Coats’ disease and Leber’s miliary aneurysms was also considered, as it typically affects males and is unilateral. Yet this diagnosis falls short due to the absence of typical exudation and the presence of peripheral perivascular sheathing which is indicative of an inflammatory component.

The treatment of Eales’ disease depends on the stage at presentation. We initiated FFA-guided laser retinal photocoagulation to the large areas of capillary non-perfusion despite the absence of neovascularization due to logistic reasons. As there was no active inflammation on presentation, we did not consider systemic or periocular steorid therapy. VEGF level in the vitreous has been found to be higher in eyes with Eales’ disease as compared to normal [1]. Although evidence is limited to a number of case reports and small case series, anti-VEGF therapy have been shown to induce regression of abnormal vessels, macular edema and exudation with better visual outcome [12]. Our patient was counseled for intravitreal anti-VEGF, however he opted out of it in view of the guarded prognosis attributed to the macular findings.

This report highlights an atypical case of Eales’ disease due to co-existing, secondary Coats’-like reaction. The Coats’-like reaction can be subtle, without clinically visible exudates.