A CASE OF EALES DISEASE OBSERVED BY WIDEFIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY

We report a case of Eales disease in which an extensive nonperfusion area, A-V shunt and retinal neovascularization were noninvasively confirmed using widefield optical coherence tomography angiography, which has a wider angle of view as compared with that for conventional instruments. Purpose: The purpose of this study was to report a 30-year-old woman with Eales disease, showing bilateral proliferative tissue. The retinal vessels were evaluated using widefield optical coherence tomography angiography (widefield OCTA), which has a wider angle of view compared with conventional instruments. Methods: This is a case report. Results: Widefield OCTA showed an extensive nonperfusion area and A-V shunt in both eyes and a vascular structure in the left eye that appeared to be retinal neovascularization. Ultra-widefield fluorescein angiography revealed no filling delay in the early phase, a vast nonperfusion area from the midperiphery to the ora serrata in bilateral eyes, and retinal neovascularization in the left eye. Based on the results of ultra-widefield angiography, OCTA examination, and systemic examination, a diagnosis of Eales disease was finally made after all the differential diseases had been excluded. Conclusion: In a patient with Eales disease, the peripheral nonperfusion area and retinal neovascularization that were consistent with the ultra-widefield angiography findings were noninvasively confirmed by widefield OCTA. Widefield OCTA is useful in the detection of peripheral changes of the fundus.

From the Department of Ophthalmology, Graduate School of Medicine, Gunma University, Maebashi, Japan.
E ales disease is characterized by occlusion of retinal vessels due to idiopathic periphlebitis, resulting in nonperfusion areas and recurrent vitreous hemorrhage. 1,2Reports from India, Southeast Asia, and Germany [2][3][4] have suggested that Eales disease is associated with an immune response to the genus Mycobacterium, as represented by Mycobacterium tuberculosis, 5,6 and autoimmune diseases. 2However, there is only limited knowledge on the pathogenesis of the disease, and thus, the diagnosis of Eales disease is currently a diagnosis of exclusion.
Our study reports a case of Eales disease in which the peripheral vascular occlusion and nonperfusion areas were noninvasively identified by optical coherence tomography (widefield OCTA; Xephilio OCT-S1; Canon, Tokyo, Japan), which has a wider angle of view as compared with that possible with conventional equipment.

Case Report
A 30-year-old woman was referred to our department with a chief complaint of blurred vision in her left eye.Her medical history included only mild anemia.On presentation, the best-corrected visual acuity was 20/16 and 20/32 in the right and left eye, respectively.The intraocular pressure was 13 mmHg bilaterally.Anterior chamber inflammation and keratic precipitates were not observed.As seen in Figure 1, A and B, ultra-widefield color fundus photographs showed hard exudate and retinal hemorrhage in the posterior pole, along with proliferative tissue over the optic disk and arcade vessels.Prominent vascular sheathing, vascular tortuosity, and A-V shunt were seen in all quadrants from the midperiphery to the ora serrata in both eyes.
None of the authors has any financial/conflicting interests to disclose.
This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reprint requests: Hideo Akiyama, MD, PhD, Department of Ophthalmology, Graduate School of Medicine, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan; e-mail: akiyamah47@gunma-u.ac.jpVitreous hemorrhage due to rupture of the retinal neovascularization was seen in the left eye.In addition to the absence of posterior vitreous detachment in both eyes, OCT showed there was a fibrovascular membrane from the optic disk to the macula and cystic change with hard exudate in the left eye (Figure 1, C and D).Widefield OCTA showed an extensive nonperfusion area and A-V shunt in both eyes, with vascular structures that appeared to be retinal neovascularization in the left eye (Figure 2, A and B).
The results of the ultra-widefield fluorescein angiography (UWFA) performed with the Optos California device (Optos, Marlborough, MA) revealed there was no filling delay in the early phase, a vast nonperfusion area from the midperiphery to the ora serrata bilaterally, and retinal neovascularization with profuse fluorescein dye leakage in the left eye (Figure 3, A and  B).Blood tests were negative for syphilis, diabetes, leukemia, severe anemia, QuantiFERON-TB Gold Plus, and T-SPOT.In addition, the patient had no respiratory symptoms with normal chest x-rays, which suggested the absence of active tuberculosis.All markers of collagen disease were negative, and the C-reactive protein level and erythrocyte sedimentation rate were within the normal range.Based on the above findings, the patient was diagnosed with Eales disease.Subsequently, laser photocoagulation was then performed on the nonperfusion areas of both eyes (Figure 4, A and B).No recurrence of vitreous hemorrhage has been identified during the 2 years since the initial visit.

Discussion
Optical coherence tomography angiography is a device that can noninvasively evaluate the vascular structure of the fundus, with the scan width and depth of the conventional device demonstrated to be approximately 12 mm and 2.0 mm, respectively.By contrast, the widefield OCTA can scan a range of approximately 23 mm in width and 5.3 mm in depth.This makes it possible to obtain high-resolution Prominent vascular sheathing, vascular tortuosity, and A-V shunt were seen in all quadrants from the midperiphery to the ora serrata.OCT B-scan image of the horizontal section in the right eye (C) shows hard exudate in the inner nuclear layer of the retina between the optic disk and the macula.OCT B-scan image of the horizontal section in the left eye (D) shows fibrovascular membrane from the optic disk to the macula and cystic change with hard exudate.images of a wide area from the vitreous cavity to the retina, choroid, and sclera.Compared with images obtained by conventional OCTA (12 • 12 mm), images acquired by widefield OCTA (Canon OCT S-1; 23 • 20 mm, about 80°) have an overwhelming amount of information, especially regarding the periphery of the fundus.Widefield OCTA is a powerful tool that can be used in retinal diseases such as diabetic retinopathy and retinal vein occlusion, which cause lesions outside the vascular arcade.In addition, the use of a swept light source improves the scanning speed and saves imaging time.The widefield OCTA used in this report can easily acquire a high-quality OCTA image by performing noise reduction processing using artificial intelligence from a single image.Furthermore, a panoramic image of approximately 110°can be obtained by taking four or five images at different fixation positions.There are some previous studies that have reported that the presence of the nonperfusion areas on UWFA is correlated with widefield OCTA. 7,8However, our study is the first report to demonstrate that the peripheral nonperfusion area and retinal neovascularization could be identified with UWFA and widefield OCTA in a patient with Eales disease.The differential diagnosis of Eales disease requires the exclusion of vascular occlusive diseases such as diabetic retinopathy, retinal vein occlusion, sarcoidosis, Behçet disease, Coats disease, familial exudative vitreoretinopathy, AIDS, tuberculosis, syphilis, and sickle cell disease. 9In particular, the differential diagnosis from tuberculosis is important.Because M. tuberculosis can sometimes spread outside of the lungs to other organs by the bloodstream, which is referred to as extrapulmonary tuberculosis, this can make it difficult to rule out tuberculosis.In our current examination, the QuantiFERON test was performed to differentiate Eales disease from tuberculous uveitis.The sensitivity of this test is 98.9%, with a negative result highly probable of a negative diagnosis. 10Thus, our subsequent ultra-widefield angiography and OC-TA examination results made it possible to determine a diagnosis of Eales disease after excluding all the differential diseases.
In summary, the peripheral nonperfusion area and retinal neovascularization that were consistent with the findings determined by the UWFA were noninvasively confirmed by widefield OCTA in a patient with Eales disease.Widefield OCTA is useful in the detection of peripheral changes of the fundus.

Fig. 1 .
Fig.1.Ultra-widefield color fundus photographs and OCT B-scan images at the initial visit.Ultra-widefield color fundus photographs of right eye (A) and left eye (B) show hard exudate and retinal hemorrhage in the posterior pole and proliferative tissue over the optic disk and arcade vessels.Prominent vascular sheathing, vascular tortuosity, and A-V shunt were seen in all quadrants from the midperiphery to the ora serrata.OCT B-scan image of the horizontal section in the right eye (C) shows hard exudate in the inner nuclear layer of the retina between the optic disk and the macula.OCT B-scan image of the horizontal section in the left eye (D) shows fibrovascular membrane from the optic disk to the macula and cystic change with hard exudate.

Fig. 2 .
Fig. 2. Widefield OCTA at the initial visit.Widefield OCTA revealed an extensive nonperfusion area in the peripheral fundus of the right eye (A) and left eye (B) and prominent retinal neovascularization in the superior temporal area (red arrow) in the left eye (B).The image is at the level of the superficial retinal layer and includes the area on the vitreous side that starts at 10 mm from the ILM and continues to the border between the IPL and the INL.

Fig. 3 .
Fig. 3. Ultra-widefield angiography with fluorescence at the initial visit.A-V shunts and an extensive nonperfusion area from the midperiphery to the ora serrata are seen in the right eye (A) and left eye (B).Retinal neovascularization with profuse fluorescein dye leakage corresponding to the abnormal vascular structure detected by widefield OCTA is observed (red arrow).

Fig. 4 .
Fig. 4. Ultra-widefield color fundus photographs and autofluorescence fundus photographs after laser photocoagulation.Retinal photocoagulation was performed for the nonperfusion area of both eyes.White to yellow laser spots can be seen in the periphery of the ultrawidefield color fundus photographs of the right eye (A) and left eye (B).Corresponding to these laser spots, autofluorescence fundus photographs of the right eye (C) and left eye (D) show dark to white spots.