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 Table of Contents  
Year : 2020  |  Volume : 58  |  Issue : 4  |  Page : 298-301

A rare case report of peri-papillary choroidal neovascularization in vogt-koyanagi-harada disease

Department of Uvea Services, Aravind Eye Hospital and Post Graduate Institute of Ophthalmology, Madurai, Tamil Nadu, India

Date of Submission02-Jun-2020
Date of Decision12-Jul-2020
Date of Acceptance20-Jul-2020
Date of Web Publication16-Dec-2020

Correspondence Address:
Dr. Sarvesswaran Prakash
Aravind Eye Hospital, 1, Anna Nagar, Madurai - 625 020, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tjosr.tjosr_67_20

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Vogt-Koyanagi-Harada (VKH) disease is a bilateral, granulomatous panuveitis with neurologic and cutaneous manifestations. Late complications include cataract, glaucoma, choroidal neovascularization (CNVM), and subretinal fibrosis; the latter two carries poor visual prognosis. We report a known case of VKH complicated with peri-papillary CNVM, who was steroid responder as well as steroid dependent, the patient had recurrent episodes of anterior uveitis with steroid-sparing immunosuppressive therapy. Because of the recurrent and uncontrolled inflammation, she developed peri-papillary CNVM in the right eye, which was effectively treated with intravitreal bevacizumab. Even though CNVM is a known complication of VKH, peri-papillary CNVM occurs very rarely and is least reported in the literature. The main therapeutic goal in VKH is to control underlying recurrent inflammation to prevent late complications.

Keywords: Bevacizumab, exudative retinal detachment, peri-papillary choroidal neovascularization, Vogt-Koyanagi-Harada disease

How to cite this article:
Prakash S, Rathinam S R. A rare case report of peri-papillary choroidal neovascularization in vogt-koyanagi-harada disease. TNOA J Ophthalmic Sci Res 2020;58:298-301

How to cite this URL:
Prakash S, Rathinam S R. A rare case report of peri-papillary choroidal neovascularization in vogt-koyanagi-harada disease. TNOA J Ophthalmic Sci Res [serial online] 2020 [cited 2022 Dec 7];58:298-301. Available from: https://www.tnoajosr.com/text.asp?2020/58/4/298/303652

  Introduction Top

Vogt-Koyanagi-Harada (VKH) disease is a bilateral, granulomatous panuveitis that affects the central nervous system, auditory, and integumentary system in its various phases. It has a predilection toward heavily pigmented race, especially Asians and Hispanics. It occurs mostly in women than in men, especially in the middle-aged population, but it can occur at any age. It is hypothesized to have autoimmune etiology with auto-antibodies against the melanosomes or the enzymes involved in the synthesis of melanin granules.[1] The diagnosis is made clinically based on the revised diagnostic criteria proposed by the first international workshop on VKH disease.[2] VKH treated with corticosteroids and other immunosuppressive agents have a good prognosis. Complications include cataract, secondary glaucoma, inflammatory choroidal neovascularization (CNVM), and subretinal fibrosis (SRF), of which the latter two have a poor visual prognosis.[3] Here, we report a young Indian woman with VKH who was a steroid responder as well as steroid-dependent complicated with peri-papillary CNVM and was effectively treated with intravitreal bevacizumab. We report this case because of its rare clinical presentation and adding to literature about peri-papillary CNVM and its effective management.

  Case Report Top

Initial presentation

A 25-year-old Indian woman presented to us in the mid of 2014 with complaints of bilateral eye pain, redness, and defective vision for 2 months with a visual acuity of 5/60 in both eyes. There was no history of trauma and no prodromal symptoms suggestive of VKH. Systemic examination of the patient was unremarkable. On ocular examination, her intraocular pressure (IOP) was 16 mm Hg bilaterally. She had active granulomatous anterior uveitis with mutton fat keratic precipitates in both eyes with cells and flared in the anterior chamber. On the posterior segment examination, both eyes had mild vitritis with hyperemic edematous disc and multiple areas of exudative retinal detachment involving the macula [Figure 1]. Ultrasonography (B-scan) in both eyes revealed multiple exudative retinal detachments with thickened retino-choroid sclera complex. Fundus fluorescein angiography in both eyes revealed multiple hypofluorescent dots in the early phase and punctate hyperfluorescent dots in the late phase, giving the characteristic starry sky appearance, with diffuse pooling of dye over the areas of retinal detachment [Figure 1]. We diagnosed her as a probable case of VKH disease according to the revised diagnostic criteria proposed by the first international workshop on VKH disease. The patient was treated with pulse dose of intravenous methyl prednisolone 1g daily for 3 days, followed by oral prednisolone 1mg/kg/day on tapering doses over 6 weeks. She responded well to initial treatment with resolution of symptoms and improvement in best-corrected visual acuity (BCVA) to 6/12 in both eyes.
Figure 1: (a and b) Fundus photography showing the right eye, left eye respectively – showing disc hyperemic and disc edema with multiple exudative retinal detachment (c and d) fundus fluorescein angiogram of the right eye showing multiple hypofluourescent dots in the early phase and punctate hyperfluourecent dots in late phase with disc leakage

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Recurrence of inflammation

There was a recurrence of symptoms and signs in both eyes as the dose of oral steroid was tapered. So she was treated with posterior subtenon (PST) injection triamcinolone acetonide (40 mg/dose) in both eyes. Her symptoms reduced, but there was a secondary increase in her IOP to 32 mm of Hg bilaterally; hence, she was labeled as steroid responder and was started on anti-glaucoma medications.

Failure of immunosuppressive chemotherapy agents

She was started on steroid-sparing immunosuppressive agents, methotrexate 20 mg/week for 6 months (June 2014–December 2014). As there was multiple recurrences of anterior uveitis over a prolonged phase of chronic posterior uveitis, methotrexate was switched over to mycophenolate mofetil 1500 mg/day for one year (December 2014–December 2015) and then to cyclophosphamide 100 mg/day for nine months (December 2015–September 2016). During this period, acute exacerbations were treated with systemic steroids on the tapering dose and local/PST injection of corticosteroid (2014–2016). Hence, the patient was labeled as steroid-dependent, and anti-glaucoma medication was continued. The patient was unaffordable for a newer biological group of drugs.

Deterioration of vision and its management

After treating her for 3 years (2014–2016) through the waxing and waning phases of chronic pan-uveitis [Figure 2] her BCVA worsened to 6/60 in the right eye. On follow-up visit in late 2017, posterior segment examination revealed tongue-shaped sub-retinal lesion in the peri-papillary region in the right eye and cup-to-disc ratio was 0.4:1 in both eyes. Ocular coherence tomography (OCT) in the right eye revealed a break in retinal pigment epithelial/Bruch's membrane complex with hyperreflective mass emanating from the choroid into sub retinal space in the peri-papillary region. Over the fovea OCT revealed para foveal intra retinal cystic fluid suggestive of peri papillary active CNVM [Figure 3]. Hence, the right eye was treated with three consecutive doses of intravitreal bevacizumab (1.25 mg/dose), each given 1 month apart. On subsequent visits, OCT-showed regression of sub-retinal fluid with significant visual improvement to BCVA of 6/12 in the right eye. In her last follow-up visit, the patient had BCVA of 6/18 and posterior subcapsular cataract in both eyes and she is currently on oral prednisolone acetate 1 mg/kg/day on tapering dosage with local steroid drops and anti-glaucoma medications, and her IOP was under control and recent OCT revealed inactive CNVM. Informed consent was obtained from patient for research and publication purposes.
Figure 2: Graphical representation of patient's timeline: red line-shows the course of pan-uveitis with multiple recurrences of anterior uveitis over a prolonged duration which is resistant to methotrexate, mycophenolate mofetil and cyclophosphamide. Blue line-shows the course of choroidal neovascularization which regressed following three doses of intra-vitreal bevacizumab

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Figure 3: (a) Fundus photography of right eye showing a tongue-shaped sub-retinal lesion – peri –papillary choroidal neovascularization, (b) ocular coherence tomography-right eye (before treatment) active choroidal neovascularization emanating from choroid with RPE/BM complex break -in the peri-papillary region with intra-retinal cystic fluid, (c) Ocular coherence tomography - right eye-(after treatment) showing regression of intra-retinal fluid

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  Discussion Top

VKH is a chronic granulomatous panuveitis with multi-systemic involvement.[4]

VKH disease consists of four phases: (1) prodromal phase, where neurologic and auditory features symptoms occur, (2) acute uveitic phase, characterized by a diffuse choroiditis, which presents as multiple exudative retinal detachments and disc edema with hyperemia, with or without signs of anterior uveitis; (3) chronic convalescent phase, inflammation reduces but the development of depigmentation occurs in limbal and fundus region to give peri-limbal vitiligo (Sugiura sign) and depigmented choroid (sunset glow fundus) with poliosis, vitiligo, and alopecia; and (4) chronic-recurrent phase, presents with iridocyclitis, which can be recurrent, chronic and mostly resistant to therapy.[3] The complications are seen primarily during the chronic convalescent, and chronic-recurrent phases that occurs due to the disease and/or its treatment, including cataract in 42%, glaucoma in 27%, CNVM in 2%–11%, and SRF in 6% and these patients had longer median duration of disease with more recurrences.[3]

The factors that increase the risk of developing CNVM are chronic recurrent anterior uveitis, which is clearly evident from our patient's timeline and fundus pigmentary changes [Figure 2].[5] The chronic inflammatory processes destroy the Bruch's membrane, which disturbs the homeostasis between inhibitory/stimulatory angiogenic factors, and mainly vascular endothelial growth factor (VEGF) stimulates the growth of the inflammatory CNVM which is generally Type 2 as it grows above the RPE.[6],[7],[8] There are many ways to treat CNVM, which includes focal laser photocoagulation, photodynamic therapy, surgical excision, and intravitreal anti-VEGF injection.[7] All these modalities cause significant collateral damage to the adjacent retina and the choroid, except anti-VEGF.[8]

CNVM per se is more common sub-foveally rather than peri-papillary region as the macular location has more predilection in inflammatory CNV.[9] Wu et al. reported that in inflammatory CNV, the non-subfoveal location was affected during the early course of disease[9], and subsequently, sub-foveal area is involved emphasizing the need for longer follow up. Pai et al.[10] reported a combination of intravitreal anti-VEGF and steroid was effective in treating recurrent inflammatory CNVM, but since our patient was a steroid responder, we treated her with intra-vitreal anti-VEGF. The number of injections needed in our patient was 3 doses of intra-vitreal anti-VEGF with each dose 1 month apart, Julián et al.[11] reported 13 eyes with sub-foveal CNVM and 2 eyes with peri-papillary CNVM and mean number of intra-vitreal anti-VEGF injection needed in uveitis-related CNVM was 4.25 with frequency one dose every 12.97 weeks.

The main therapeutic goal in VKH is to control underlying recurrent inflammation with immunosuppression so that the most debilitating complications such as CNVM and SRF can be prevented. Inflammatory CNVM rarely presents over the peri-papillary region and with increased risk to involve the sub-foveal region during the late course of the disease. It can be treated effectively with a combination of intravitreal anti-VEGF drugs and immunosuppressive agents.[12]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Read RW, Rao NA, Cunningham ET. Vogt-Koyanagi-Harada disease. Curr Opin Ophthalmol 2000;11:437-42.  Back to cited text no. 1
Read RW, Holland GN, Rao NA, Tabbara KF, Ohno S, Arellanes-Garcia L, et al. Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: Report of an international committee on nomenclature. Am J Ophthalmol 2001;131:647-52.  Back to cited text no. 2
Moorthy RS, Inomata H, Rao NA. Vogt-Koyanagi-Harada syndrome. Surv Ophthalmol 1995;39:265-92.  Back to cited text no. 3
Lertsumitkul S, Whitcup SM, Nussenblatt RB, Chan CC. Subretinal fibrosis and choroidal neovascularization in Vogt-Koyanagi-Harada syndrome. Graefes Arch Clin Exp Ophthalmol 1999;237:1039-45.  Back to cited text no. 4
Moorthy RS, Chong LP, Smith RE, Rao NA. Subretinal neovascular membranes in Vogt-Koyanagi-Harada syndrome. Am J Ophthalmol 1993;116:164-70.  Back to cited text no. 5
Tatar O, Yoeruek E, Szurman P, Bartz-Schmidt KU, Tübingen Bevacizumab Study Group, Adam A, et al. Effect of bevacizumab on inflammation and proliferation in human choroidal neovascularization. Arch Ophthalmol 2008;126:782-90.  Back to cited text no. 6
Mansour AM, Arevalo JF, Ziemssen F, Mehio-Sibai A, Mackensen F, Adan A, et al. Long-term visual outcomes of intravitreal bevacizumab in inflammatory ocular neovascularization. Am J Ophthalmol 2009;148:310-600.  Back to cited text no. 7
Mathur G, George AE, Sen P. Paediatric choroidal neovascular membrane secondary to toxoplasmosis treated successfully with anti-vascular endothelial growth factor. Oman J Ophthalmol 2014;7:141-3.  Back to cited text no. 8
[PUBMED]  [Full text]  
Wu K, Zhang X, Su Y, Ji Y, Zuo C, Li M, et al. Clinical characteristics of inflammatory choroidal neovascularization in a chinese population. Ocul Immunol Inflamm 2016;24:261-7.  Back to cited text no. 9
Pai SA, Hebri SP, Lootah AM. Management of recurrent inflammatory choroidal neovascular membrane secondary to Vogt-Koyanagi-Harada syndrome, using combined intravitreal injection of bevacizumab and triamcinolone acetate. Indian J Ophthalmol 2012;60:551-2.  Back to cited text no. 10
[PUBMED]  [Full text]  
Julián K, Terrada C, Fardeau C, Cassoux N, Français C, LeHoang P, et al. Intravitreal bevacizumab as first local treatment for uveitis-related choroidal neovascularization: Long-term results. Acta Ophthalmol 2011;89:179-84.  Back to cited text no. 11
Dʼsouza P, Ranjan R, Babu U, Kanakath AV, Saravanan VR. Inflammatory choroidal neovascular membrane: Long-term visual and anatomical outcomes after intravitreal anti-vascular endothelial growth factor therapy. Retina 2018;38:1307-15.  Back to cited text no. 12


  [Figure 1], [Figure 2], [Figure 3]


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